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A wide-ranging study published this past week in the Journal of the American Medical Association found that older people, women, Black and Latinx individuals, and patients with lower household incomes were less likely to use video for low price zithromax telemedicine care during the early phase of the buy antibiotics zithromax. The cohort study, which researchers called "the first large-scale study to characterize inequitable access to telemedical care," relied on data from nearly 150,000 unique patients who scheduled telemedicine low price zithromax visits from March 16 to May 11, 2020. It found that older patients, Asian people, and non-English-speaking individuals had lower rates of completed telemedicine visits. "Telemedicine has the potential to be low price zithromax leveraged to increase access to care among patient groups that may have traditionally faced barriers to in-person care," wrote researchers.

"However, we must be intentional with implementation to ensure that all patients are equipped to effectively participate in telemedicine care." WHY IT MATTERS The research team from the University of Pennsylvania health system sought to compare the demographic characteristics of patients who completed a telemedicine encounter (either via phone or low price zithromax video) with those who were scheduled for one, but did not complete it. Using the electronic health record, the team extracted demographic information for adult patients scheduled at UPenn's health system’s primary care and medical specialty clinics for telemedicine care in the first few months of the zithromax.A total of 148,402 patients were scheduled during the study period. Of those, 80,780 (54.4%) completed a telemedicine encounter and 67,622 had a canceled or no-show visit.Slightly less than half of the patients who showed up to their telemedicine encounters used video for their visits, and about 54% used telephone for low price zithromax their appointments. Although patients with completed telemedicine visits were more likely to be female, women had lower rates of using telemedicine for specialty care and of using video for virtual calls overall.Researchers noted that this may have been due to women bearing a disproportionate burden of childcare during the zithromax, perhaps limiting their time to engage with specialty virtual care.Younger patients, those with commercial insurance, English-speaking patients and non-Asian patients were more likely to complete their visits, while patients who used video were more likely to be younger, white, and to have a higher median household income.

Researchers noted that these low price zithromax numbers reflect existing medical inequities and could exacerbate them."The buy antibiotics zithromax has devastated communities of color and marginalized populations, exposing the deep inequities of our U.S. Healthcare system," they low price zithromax wrote. "The findings of this study demonstrate that significant inequities are also present among patients in accessing necessary telemedicine care." THE LARGER TREND Like other digital tools, telemedicine offers not just opportunities to address the digital divide, but also the potential to widen it. Some studies low price zithromax have suggested, for example, that Black and Latino patients in New York City were less likely to use telehealth during the zithromax, while others have said Black people were more likely to use virtual care.Regardless, lawmakers and advocates say it's vital to work toward expanding access to virtual care.

Rep. Anna Eshoo, D-Calif., who chairs the House Energy and low price zithromax Commerce Subcommittee on Health, said this past October that "obviously we need the expansion of broadband" to make that access happen. But it will take coverage parity too, she added low price zithromax. On the Medicare side, she said, "We have to ensure that when we make [telehealth] permanent that … cutting-edge technologies are part of the reimbursement.

Otherwise telehealth won't work." ON THE RECORD "As we develop and refine our telemedicine practice, we must low price zithromax intentionally design our system to mitigate inequity. Engagement with community members from vulnerable populations to design and tailor connected health technologies is essential to ensure accessibility for all patients," wrote the UPenn researchers in the JAMA study. "Although many low price zithromax have anxiously awaited a return to 'normal,' we must acknowledge that our previous 'normal' was a U.S. Healthcare system and digital connectivity landscape fraught low price zithromax with inequity.

As we build our telemedical health system, which is likely here to stay, a new 'normal' must prioritize the needs of those who have been historically marginalized to ensure that health equity is achieved," they added. Kat Jercich is senior editor of Healthcare low price zithromax IT News.Twitter. @kjercichHealthcare IT News is a HIMSS Media publication.Part of Appalachian Regional Healthcare System, Wautaga Medical Center in rural Boone, North Carolina, already was busy before buy antibiotics hit, and leadership knew their current hospitalist staff low price zithromax could not handle the onslaught of patients coming through during the zithromax.THE PROBLEMThe medical center was looking for a solution that would help provide staffing for the 12-hour day shift. Wautaga already had three inpatient teams and was looking for a telemedicine company to handle a fourth.The nearest tertiary referral hospital is 90 minutes away, and half of the time helicopters are not able to fly there because of extreme weather.

Watauga Medical Center is a Medicare five-star-rated hospital and wanted a telehealth company that could provide the same high quality of care.On a related note, Cannon Memorial Hospital in Linville, North low price zithromax Carolina, also is part of Appalachian Regional Healthcare System, and it has been using telemedicine vendor Telehealth Solution for three years, for both daytime rounding service, with a physician assistant or nurse practitioner, and full nocturnist coverage."At Cannon, we provide both daytime supervision for the ACP on site and MD coverage at nighttime for both cross coverage calls and admissions," said Dr. Lisa Kaufmann, director of hospital medicine at Appalachian Regional Healthcare System. "This has helped low price zithromax reduce overall cost for Watauga staffing while giving access to an MD expertise for patients.""It is extremely hard to find high-quality locum physicians – our decision to use the telemedicine solution was more about saving patient lives than saving money."Dr. Lisa Kaufmann, Appalachian Regional Healthcare SystemWatauga Medical Center, which is the main hospital, low price zithromax did not use Telehealth Solution's services until it was hit hard with buy antibiotics. "They began as a PRN service and currently have a telehealth service every day," Kaufmann said.PROPOSALThe proposal was to help with patient volume surges and reduce exposure of clinicians (MDs and ACPs) to buy antibiotics , ensuring clinical care/coverage for patients is stable and predictable."The vendor provided the ability to follow clinical protocols as developed by Watauga clinical leadership," Kaufmann explained.

"We needed to work with a company that has a seamless process of direct charting into our patients' EHRs, just as if they were on site. We did not want the hassle of low price zithromax having to learn a whole new system/charting procedure and having to input records manually into our own charting system."MARKETPLACEThere are many vendors of telemedicine technology and services on the health IT market today. Healthcare IT News recently compiled a comprehensive list of these vendors with detailed descriptions. To read this special report, click here.MEETING THE CHALLENGE"We looked at a few national companies, but they were very costly low price zithromax and rigid in their requirements," Kaufmann said of the telehealth vendor search.

"They would not use our hospital's medical records, and they wanted to send us a specific document that we need to configure on our own to be able to incorporate into our own records."It would have taken more time than it was worth, as we were trying to find a company that would work with our low price zithromax hospital seamlessly and quickly, and we couldn't afford to have the downtime, especially during the zithromax."When Watauga met with Telehealth Solution, everything was simple and streamlined, she added. The company does all of its orders and charting in an existing EHR with no interface needed, she said."It improves patient safety as well as workflow on our end," she said. "It is much better than being given a document that needs to be referenced and hunted down in the hospital's electronic low price zithromax files. There was no extra work on our end, which was a true game-changer.

It made our decision very easy."Telehealth Solution works with hospitals in rural towns across the low price zithromax country. With lean staffs, rural hospitals need something that requires minimal IT interface builds, she said."They provide custom technology and staff training so that we can access a virtual low price zithromax Telehealth Solution provider whenever we need to," she explained."With the push of a button on the nurse-friendly telemedicine cart, a provider appears on the screen to perform a patient evaluation with assistance from the nurse. The virtual physician can remotely view the patient's medical history and charts, order treatment modalities, attend multidisciplinary rounds, have family meetings and discharge our patients."RESULTSAt Watauga, the success has been with the additional patients that the organization has been able to care for during the zithromax. On average, the medical center has had between 12 and 18 telehealth patient encounters per day since starting clinical coverage for Watauga."The vendor provided a daily virtual team staffed by a nurse practitioner or physician's low price zithromax assistant with supervision by a hospitalist who sees every patient on the service," Kaufmann explained.

"The telehealth cart includes a high-resolution camera and low price zithromax an electronic stethoscope, which permits a much better physical examination of the patient than can be done with tablets."What telehealth did for us was much more important than cost savings of having to hire an extra hospitalist. They made it possible to staff Cannon Memorial and keep it open to medical patients. Preserving a critical access hospital for the people who need care in this rural area is a very big deal."In the same way, at Watauga Medical Center staff had low price zithromax no way to quickly find additional on-site physicians in this rural area. Telehealth is helping to make it possible to take care of what soon will be twice the medical center's normal number of patients."The point is not only that it is more cost-efficient to hire telehealth than locum physicians," Kaufmann said.

"Also, it is extremely hard to find high-quality locum physicians – our decision to use the telemedicine solution was more about low price zithromax saving patient lives than saving money. There is no place in Western North Carolina during the current surge that is able to accept transfers."Twitter low price zithromax. @SiwickiHealthITEmail the writer. Bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication.This week population health and genomics company Color became digital health’s low price zithromax latest unicorn after scoring $167 million in Series D funding.

General Catalyst led the round with participation from funds and accounts advised by T. Rowe Price Associates and Viking Global Investors.The company now boasts of low price zithromax $278 million in financing with a valuation of $1.5 million.WHAT IT DOES HIMSS20 DigitalLearn on-demand, earn credit, find products and solutions. Get Started low price zithromax >>. Color created a digital infrastructure for public health institutions and initiatives.

The company’s model is based on teaming up public health agencies, research institutions, employer organizations, health systems and health stakeholders.Its clients can access a custom-built software that was designed to low price zithromax integrate with laboratory results and is HIPAA compliant. As part of its services the startup is able to provide genetic testing results for genes associated with an increased risk of common hereditary cancers and high cholesterol.According to its website, the company is able to share anonymized genetic information with public variant databases. If participants give permission, the low price zithromax system is also able to share the information with research collaborations.According to the company, the service is able to integrate into physician ordering, and users can get genetic counseling after being tested.More recently, the company has worked with buy antibiotics testing efforts. The company offers not just testing, but also low price zithromax surveillance for population health.

It has teamed up with PerkinElmer and the State of California to work on these testing efforts.WHAT IT’S FORThe company plans on adding new members to its leadership team and scaling its operation. The company has hired Claire Vo as its next chief product officer, Emily Reuter as its next vice president of strategy and operations and Ashley Chandler as vice president of marketing.MARKET SNAPSHOTColor previously made headlines when it teamed up with the National low price zithromax Institutes of Health for its All of Us program – a national research project dedicated to collecting data from a diverse population for prevention and treatment of diseases.The NIH awarded Color $4.6 million in grant funding for providing program participants with findings on ancestry, traits, drug-gene interactions (pharmacogenomics) and genes connected with high-risk diseases.Public health initiatives that combine genomics are becoming increasingly popular. In Finland, the FinnGen Project, a public-private research partnership, aims to bring 500,000 genomic samples (covering roughly 10% of the Finnish population) together with health records in order to help understand the origins of disease, prioritize drug treatments and come up with new therapies..

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Lauren Gambill, MDPediatrician, AustinMember, Texas Medical Association (TMA) Committee on Child and Adolescent HealthExecutive Board Member, Texas Pediatric SocietyDoctors find out are community zithromax for pneumonia leaders. This role has become even more important during the buy antibiotics zithromax. As patients navigate our new reality, they are looking to us to determine what is safe, how to protect their families, and the future of their zithromax for pneumonia health care.

As more Texans lose their jobs, their health insurance, or even their homes, it is crucial that Texas receives the resources it needs to uphold our social safety net. The U.S. Census helps determine funding for those resources, zithromax for pneumonia and that is why it is of the upmost importance that each and every Texan, no matter address, immigration status, or age, respond to the 2020 U.S.

Census. The deadline has been cut zithromax for pneumonia short one month and now closes Sept. 30.buy antibiotics has only increased the importance of completing the census to help our local communities and economies recover.

The novel antibiotics has inflicted unprecedented strain on patients and exacerbated inequality as more people are out of work and are many in need of help with food, health care, housing, and more. Schools also zithromax for pneumonia have been stretched thin, with teachers scrambling to teach students online. Yet, the amount of federal funding Texas has available today to help weather this emergency was driven in part by the census responses made a decade ago.

Getting an accurate count in 2020 will help Texans prepare for the decade to follow, the first few years of which most certainly will be spent rebuilding from the zithromax’s fallout. Therefore, it is vital that all Texans be counted.The federal zithromax for pneumonia dollars Texas receives generally depends on our population. A George Washington University study recently found that even a 1% undercount can lead to a $300 million loss in funding.Take Medicaid, for example.

Federal funds pay for 60% of the state’s program, which provides health coverage for two out of five Texas children, one in three individuals with disabilities, and 53% zithromax for pneumonia of all births. The complicated formula used to calculate the federal portion of this funding depends on accurate census data. If Texas’ population is undercounted, Texans may appear better off financially than they really are, resulting in Texas getting fewer federal Medicaid dollars.

If that happens, lawmakers will have to make up the difference, with cuts in services, program eligibility, or physician and provider payments, any of which are potentially detrimental.The census data also is key to funding other aspects of a community’s social safety net:Health careThe Children’s Health Insurance Program (CHIP) provides low-cost health insurance to children whose zithromax for pneumonia parents make too much to qualify for Medicaid, but not enough to afford quality coverage. Like Medicaid, how much money the federal government reimburses the state for the program depends in part on the census.Maternal and child health programs that promote public health and help ensure children are vaccinated relies on data from the census. Texas also uses this federal funding to study and respond to maternal mortality and perinatal depression.Food and housing As unemployment rises and families struggle financially, many live with zithromax for pneumonia uncertainty as to where they will find their next meal.

Already, one in seven Texans experiences food insecurity, and 20% of Texas children experience hunger. Food insecurity is rising in Texas as the zithromax continues. The Central Texas Food Bank zithromax for pneumonia saw a 206% rise in clients in March.

Funding for the Supplemental Nutrition Assistance Program and school lunch programs are both determined by the census. Funding for local housing programs also is calculated via the census. An accurate count will help ensure zithromax for pneumonia that people who lose their homes during this economic crisis have better hope of finding shelter while our communities recover.

Homelessness is closely connected with declines in overall physical and mental health.Childcare and educationAs we navigate the new reality brought on by antibiotics, more parents are taking on roles as breadwinner, parent, teacher, and caretaker. This stress highlights the desperate need for affordable zithromax for pneumonia childcare. The census determines funding for programs like Head Start that provide comprehensive early childhood education to low-income families.

The good news is you still have time to complete the census. Visit 2020census.gov to take it zithromax for pneumonia. It takes less than five minutes to complete.

Then talk to zithromax for pneumonia your family, neighbors, and colleagues about doing the same. If you are wondering who counts, the answer is everyone, whether it’s a newborn baby, child in foster care, undocumented immigrant, or an individual experiencing homelessness.Completing the census is one of the best things that you can do for the health of your community, especially during the zithromax. Thank you for helping Texas heal and for supporting these essential safety net programs.(L to R).

UTHSA medical students Swetha Maddipudi, Brittany Hansen, Charles Wang, Carson Cortino, faculty advisor Kaparaboyna Kumar, MD, Ryan Wealther, Sidney Akabogu, Irma Ruiz, and Frank Jung pose with the TMA Be Wise zithromax for pneumonia Immunize banner. Photo courtesy by Ryan WealtherRyan WealtherMedical Student, UT Health San Antonio Long School of MedicineStudent Member, Texas Medical AssociationEditor’s Note. August is National Immunization Awareness Month.

This article is part of a Me&My Doctor series highlighting and promoting the use of vaccinations.“Can the flu shot zithromax for pneumonia give you the flu?. €â€œIs it dangerous for pregnant women to get a flu shot?. €â€œCan treatments zithromax for pneumonia cause autism?.

€These were questions women at Alpha Home, a residential substance abuse rehabilitation center in San Antonio, asked my fellow medical students and me during a flu treatment discussion. It is easy to see why these questions were asked, as treatment misinformation is common today.UTHSA medical student Frank Jing (left) gets a treatment fromKaparaboyna Kumar, MD, (right).Photo courtesy of Ryan Wealther“No” is the answer to all the questions. These were exactly the types of myths we set out to dispel at our vaccination drive.UT Health San Antonio Long School of Medicine medical students (under the supervision of Kaparaboyna Ashok Kumar, MD, faculty advisor for the Texas Medical Association Medical Student Section at UT Health San Antonio) hosted the treatment drive at Alpha Home with the support of TMA’s Be Wise – Immunize℠ program, a public health initiative that aims to increase vaccinations and treatment zithromax for pneumonia awareness through shot clinics and education.

Our program consisted of a vaccination drive and an interactive, educational presentation that addressed influenza, common flu shot questions, and general treatment myths. The Alpha Home residents could ask us questions during the program.We were interested to see if our educational program could answer Alpha Home residents’ questions about zithromax for pneumonia vaccinations and allay their hesitations about getting a flu vaccination. To gauge this, we created a brief survey.(Before I discuss the results of the survey, I should define treatment hesitancy.

treatment hesitancy is a concept defined by the World Health Organization. It relates to when patients do not vaccinate zithromax for pneumonia despite having access to treatments. treatment hesitancy is a problem because it prevents individuals from receiving their vaccinations.

That makes them more susceptible to getting sick from treatment-preventable diseases.)We surveyed the residents’ opinions about vaccinations before and after our educational program. While opinions about shots improved with each survey question, we saw the most significant attitude change reflected in answers to the questions “I am concerned that vaccinations might not be safe,” and “How zithromax for pneumonia likely are you to receive a flu shot today?. € We had informed the residents and improved their understanding and acceptance of immunizations.Post-survey results show more residents at the Alpha Home shifted to more positive attitudes about treatments, after learning more about their effectiveness by trusted members of the medical community.

Graph by Ryan zithromax for pneumonia WealtherWhy is this important?. First, our findings confirm what we already knew. Education by a trusted member of the medical community can effect change.

In fact, it is widely known that physician recommendation of vaccination is one of the most critical factors affecting whether patients receive an influenza vaccination zithromax for pneumonia. Perhaps some added proof to this is that a few of the Alpha Home residents were calling me “Dr. Truth” by the end of zithromax for pneumonia the evening.Second, our findings add to our understanding of adult treatment hesitancy.

This is significant because most of what we know about treatment hesitancy is limited to parental attitudes toward their children’s vaccinations. Some parents question shots for their children, and many of the most deadly diseases we vaccinate against are given in childhood, including polio, tetanus, measles, and whooping cough shots. However, adults need some vaccinations as well, like the yearly zithromax for pneumonia influenza treatment.

After taking part in the UTHSA educational program, more residents at the Alpha Home shared more willingness to receive the flu treatment. Graph by Ryan WealtherAnother reason improving attitudes is important is that receiving a flu shot is even more timely during the buy antibiotics zithromax because it decreases illnesses and conserves health care resources. Thousands of people zithromax for pneumonia each year are hospitalized from the flu, and with hospitals filling up with antibiotics patients, we could avoid adding dangerously ill flu patients to the mix.

Lastly, these findings are important because once a buy antibiotics vaccination becomes available, more people might be willing to receive it if their overall attitude toward immunizations is positive. Though the buy antibiotics treatment is still in zithromax for pneumonia development, it is not immune to treatment hesitancy. Recent polls have indicated up to one-third of Americans would not receive a buy antibiotics treatment even if it were accessible and affordable.

Work is already being done to try to raise awareness and acceptance. In addition, misinformation about the buy antibiotics treatment is zithromax for pneumonia circulating widely. (Someone recently asked me if the buy antibiotics treatment will implant a microchip in people, and I have seen the same myth circulating on social media.

It will not.) This myth, however, illustrates the need for health care professionals to answer patients’ questions and to assuage their concerns.treatments work best when many people in a community receive them, zithromax for pneumonia and treatment hesitancy can diminish vaccination rates, leaving people who can't get certain treatments susceptible to these treatment-preventable diseases. For example, babies under 6 months of age should not receive a flu shot, so high community vaccination rates protect these babies from getting sick with the flu. Our educational program at Alpha Home is just one example of how health care professionals can increase awareness and acceptance of shots.

As the buy antibiotics zithromax progresses, we need to ensure children zithromax for pneumonia and adults receive their vaccinations as recommended by their physician and the Centers for Disease Control and Prevention. I encourage readers who have questions about the vaccinations they or their child may need to talk with their physician. As health care professionals, we’re more than happy to answer your questions..

Lauren Gambill, MDPediatrician, AustinMember, Texas Medical Association (TMA) Committee on Child and low price zithromax Adolescent https://bugeysud-tourisme.fr/how-to-order-propecia-online/ HealthExecutive Board Member, Texas Pediatric SocietyDoctors are community leaders. This role has become even more important during the buy antibiotics zithromax. As patients navigate our new reality, they are looking to us to determine what is safe, how low price zithromax to protect their families, and the future of their health care.

As more Texans lose their jobs, their health insurance, or even their homes, it is crucial that Texas receives the resources it needs to uphold our social safety net. The U.S. Census helps determine funding for those resources, and that is why it is of the upmost importance that each low price zithromax and every Texan, no matter address, immigration status, or age, respond to the 2020 U.S.

Census. The deadline has been low price zithromax cut short one month and now closes Sept. 30.buy antibiotics has only increased the importance of completing the census to help our local communities and economies recover.

The novel antibiotics has inflicted unprecedented strain on patients and exacerbated inequality as more people are out of work and are many in need of help with food, health care, housing, and more. Schools also have been stretched thin, low price zithromax with teachers scrambling to teach students online. Yet, the amount of federal funding Texas has available today to help weather this emergency was driven in part by the census responses made a decade ago.

Getting an accurate count in 2020 will help Texans prepare for the decade to follow, the first few years of which most certainly will be spent rebuilding from the zithromax’s fallout. Therefore, it low price zithromax is vital that all Texans be counted.The federal dollars Texas receives generally depends on our population. A George Washington University study recently found that even a 1% undercount can lead to a $300 million loss in funding.Take Medicaid, for example.

Federal funds pay low price zithromax for 60% of the state’s program, which provides health coverage for two out of five Texas children, one in three individuals with disabilities, and 53% of all births. The complicated formula used to calculate the federal portion of this funding depends on accurate census data. If Texas’ population is undercounted, Texans may appear better off financially than they really are, resulting in Texas getting fewer federal Medicaid dollars.

If that happens, lawmakers will have to make up the difference, with cuts in services, program eligibility, or physician and provider payments, any of which are potentially detrimental.The census data also is key low price zithromax to funding other aspects of a community’s social safety net:Health careThe Children’s Health Insurance Program (CHIP) provides low-cost health insurance to children whose parents make too much to qualify for Medicaid, but not enough to afford quality coverage. Like Medicaid, how much money the federal government reimburses the state for the program depends in part on the census.Maternal and child health programs that promote public health and help ensure children are vaccinated relies on data from the census. Texas also uses this federal funding to study low price zithromax and respond to maternal mortality and perinatal depression.Food and housing As unemployment rises and families struggle financially, many live with uncertainty as to where they will find their next meal.

Already, one in seven Texans experiences food insecurity, and 20% of Texas children experience hunger. Food insecurity is rising in Texas as the zithromax continues. The Central low price zithromax Texas Food Bank saw a 206% rise in clients in March.

Funding for the Supplemental Nutrition Assistance Program and school lunch programs are both determined by the census. Funding for local housing programs also is calculated via the census. An accurate count will help ensure that people who lose their homes during this economic crisis have better hope of finding low price zithromax shelter while our communities recover.

Homelessness is closely connected with declines in overall physical and mental health.Childcare and educationAs we navigate the new reality brought on by antibiotics, more parents are taking on roles as breadwinner, parent, teacher, and caretaker. This stress highlights the desperate low price zithromax need for affordable childcare. The census determines funding for programs like Head Start that provide comprehensive early childhood education to low-income families.

The good news is you still have time to complete the census. Visit 2020census.gov to take it low price zithromax. It takes less than five minutes to complete.

Then talk to low price zithromax your family, neighbors, and colleagues about doing the same. If you are wondering who counts, the answer is everyone, whether it’s a newborn baby, child in foster care, undocumented immigrant, or an individual experiencing homelessness.Completing the census is one of the best things that you can do for the health of your community, especially during the zithromax. Thank you for helping Texas heal and for supporting these essential safety net programs.(L to R).

UTHSA medical students Swetha Maddipudi, low price zithromax Brittany Hansen, Charles Wang, Carson Cortino, faculty advisor Kaparaboyna Kumar, MD, Ryan Wealther, Sidney Akabogu, Irma Ruiz, and Frank Jung pose with the TMA Be Wise Immunize banner. Photo courtesy by Ryan WealtherRyan WealtherMedical Student, UT Health San Antonio Long School of MedicineStudent Member, Texas Medical AssociationEditor’s Note. August is National Immunization Awareness Month.

This article is part of a Me&My Doctor series highlighting and promoting the use of vaccinations.“Can the flu low price zithromax shot give you the flu?. €â€œIs it dangerous for pregnant women to get a flu shot?. €â€œCan treatments cause low price zithromax autism?.

€These were questions women at Alpha Home, a residential substance abuse rehabilitation center in San Antonio, asked my fellow medical students and me during a flu treatment discussion. It is easy to see why these questions were asked, as treatment misinformation is common today.UTHSA medical student Frank Jing (left) gets a treatment fromKaparaboyna Kumar, MD, (right).Photo courtesy of Ryan Wealther“No” is the answer to all the questions. These were exactly the types of myths we set out to dispel at our vaccination drive.UT Health San Antonio Long School of Medicine medical students (under the supervision of Kaparaboyna Ashok Kumar, MD, faculty advisor for the Texas Medical Association Medical Student Section at UT Health San Antonio) hosted the treatment drive low price zithromax at Alpha Home with the support of TMA’s Be Wise – Immunize℠ program, a public health initiative that aims to increase vaccinations and treatment awareness through shot clinics and education.

Our program consisted of a vaccination drive and an interactive, educational presentation that addressed influenza, common flu shot questions, and general treatment myths. The Alpha Home residents could ask us questions during the program.We were interested to see if low price zithromax our educational program could answer Alpha Home residents’ questions about vaccinations and allay their hesitations about getting a flu vaccination. To gauge this, we created a brief survey.(Before I discuss the results of the survey, I should define treatment hesitancy.

treatment hesitancy is a concept defined by the World Health Organization. It relates to when patients do not vaccinate despite having access to low price zithromax treatments. treatment hesitancy is a problem because it prevents individuals from receiving their vaccinations.

That makes them more susceptible to getting sick from treatment-preventable diseases.)We surveyed the residents’ opinions about vaccinations before and after our educational program. While opinions about shots improved with each survey question, we low price zithromax saw the most significant attitude change reflected in answers to the questions “I am concerned that vaccinations might not be safe,” and “How likely are you to receive a flu shot today?. € We had informed the residents and improved their understanding and acceptance of immunizations.Post-survey results show more residents at the Alpha Home shifted to more positive attitudes about treatments, after learning more about their effectiveness by trusted members of the medical community.

Graph by Ryan WealtherWhy is this important? low price zithromax. First, our findings confirm what we already knew. Education by a trusted member of the medical community can effect change.

In fact, it is widely known that physician recommendation of vaccination is one of the most critical factors affecting whether patients receive an influenza low price zithromax vaccination. Perhaps some added proof to this is that a few of the Alpha Home residents were calling me “Dr. Truth” by the end of the evening.Second, our findings add to our understanding low price zithromax of adult treatment hesitancy.

This is significant because most of what we know about treatment hesitancy is limited to parental attitudes toward their children’s vaccinations. Some parents question shots for their children, and many of the most deadly diseases we vaccinate against are given in childhood, including polio, tetanus, measles, and whooping cough shots. However, adults need low price zithromax some vaccinations as well, like the yearly influenza treatment.

After taking part in the UTHSA educational program, more residents at the Alpha Home shared more willingness to receive the flu treatment. Graph by Ryan WealtherAnother reason improving attitudes is important is that receiving a flu shot is even more timely during the buy antibiotics zithromax because it decreases illnesses and conserves health care resources. Thousands of people each year are hospitalized from the flu, and with hospitals filling up with antibiotics low price zithromax patients, we could avoid adding dangerously ill flu patients to the mix.

Lastly, these findings are important because once a buy antibiotics vaccination becomes available, more people might be willing to receive it if their overall attitude toward immunizations is positive. Though the low price zithromax buy antibiotics treatment is still in development, it is not immune to treatment hesitancy. Recent polls have indicated up to one-third of Americans would not receive a buy antibiotics treatment even if it were accessible and affordable.

Work is already being done to try to raise awareness and acceptance. In addition, misinformation about the buy antibiotics treatment low price zithromax is circulating widely. (Someone recently asked me if the buy antibiotics treatment will implant a microchip in people, and I have seen the same myth circulating on social media.

It will not.) This myth, however, low price zithromax illustrates the need for health care professionals to answer patients’ questions and to assuage their concerns.treatments work best when many people in a community receive them, and treatment hesitancy can diminish vaccination rates, leaving people who can't get certain treatments susceptible to these treatment-preventable diseases. For example, babies under 6 months of age should not receive a flu shot, so high community vaccination rates protect these babies from getting sick with the flu. Our educational program at Alpha Home is just one example of how health care professionals can increase awareness and acceptance of shots.

As the buy antibiotics zithromax progresses, we need to ensure children and adults receive their vaccinations as recommended by their physician and the Centers for low price zithromax Disease Control and Prevention. I encourage readers who have questions about the vaccinations they or their child may need to talk with their physician. As health care professionals, we’re more than happy to answer your questions..

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How to get zithromax z pak

IntroductionCurrently, type 1 http://neocapital.com.ec/?p=1 diabetes mellitus (T1DM) is defined as an autoimmune disorder classically characterised by pancreatic islet beta-cell destruction triggered by autoreactive T cells, resulting in subsequent severe insulin deficiency and lifelong reliance on exogenous insulin.1 2 This autoimmune diabetes accounts for 5%–19% of diabetes and represents the main how to get zithromax z pak form of diabetes in children and adolescents.3 Its incidence is increasing worldwide at a rate of 2%–5% per year.4 This rising incidence and multiple severe diabetic complications lead to increased mortality and morbidity and aggravate the economic burden of the disease. It is accepted that the interplay between genetic factors and environmental precipitators, including ancestry and geographic location, viral and bacterial s, vitamin D, hygiene and microbiota, leads to specific tissue inflammation, namely, insulitis, insulin-producing cell death and consequent clinical disease.5–9The genetic component of T1DM can be demonstrated by the fact that siblings and offspring of patients with T1DM have a higher risk than the general population, and disease concordance in identical twins is higher than that in dizygotic twins.10 11 Over the past few years, genome-wide association study (GWAS), which measures and analyses a million or more DNA sequence variations in known linkage regions in unrelated individuals, have identified at least 58 susceptible loci combined with linkage analysis and candidate gene studies (figure 1).12–14 Most of the identified variants are common (minor allele frequency (MAF) >5%) and have modest effects (OR <1.5), although the effects of susceptibility genes such as human leucocyte antigen (HLA), insulin (INS) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) are stronger (figure 1).13 The HLA region (OR >6), located on human chromosome 6p21 and identified by linkage analysis, accounts for how to get zithromax z pak the largest proportion of T1DM heritability and explains approximately 50% of genetic T1DM risk.15 In addition to HLA, variants within the INS and PTPN22 loci, which were first identified by candidate gene studies, have larger effect sizes (OR >2) than other variants.13 The INS gene on human chromosome 11p15.5 offers the next strongest genetic risk association with T1DM after HLA and accounts for approximately 10% of genetic susceptibility to T1DM.16 It is believed that ‘missing heritability’ can be at least partially elucidated by rare and low-frequency variants (rare variants defined as variants with MAF ≤1% and low-frequency variants defined as variants with MAF=1%–5%), and some findings have indicated that rare variants have larger effect sizes than common variants.17–19 From an evolutionary standpoint, risk variants with higher penetrance are more likely to be rare due to negative selection. Taking an extreme example, monogenic/Mendelian disorders such as how to get zithromax z pak autoimmune polyendocrinopathy syndrome type I are caused by rare variants with large effect sizes and high penetrance. Intriguingly, recent and previous studies focusing on the identification of rare and low-frequency variants involved in T1DM have found a handful of such variants, and some of them do have large effect sizes.13 20–23Candidate genes or loci of type 1 diabetes mellitus (T1DM) and their ORs (the yellow bars represent the rare and low-frequency genetic variants of T1DM).76–79 " data-icon-position data-hide-link-title="0">Figure 1 Candidate genes or loci of type 1 diabetes mellitus (T1DM) and their ORs (the yellow bars represent the rare and low-frequency genetic variants of T1DM).76–79However, some studies suggest that most rare variants have only small or modest effects.24 Therefore, it remains to be seen whether the tendency of rare and low-frequency variants to have large effects is a universal phenomenon. Even though its practical value in clinical medicine may be restricted if the hypothesis that most rare variants have only a small effect is true, there is still intrinsic value how to get zithromax z pak in this field.

Such studies can lead to the discovery of new candidate how to get zithromax z pak genes implicated in disorders or human phenotypes25 and determine causal genes in candidate regions identified by GWAS. Other than understanding better its pathophysiology, new loci could lead to the identification of new biomarkers or represent drug targets for T1DM.Identifying rare and low-frequency variantsRecently, advances in next-generation DNA sequencing technologies as well as bioinformatic tools and methods to process and analyse the resulting data have enhanced the ability of researchers to find rare variants, and the decreasing cost of these technologies has made it feasible to apply them to related studies (table 1).26 The most comprehensive approach is high-depth whole-genome sequencing (WGS) due to its excellent coverage. However, high costs and multiple computational challenges have restricted its application.21 In addition to WGS with how to get zithromax z pak high or low depth, SNP-array genome-wide genotyping and imputation has been used to identify rare variants. Notably, current sequencing depth (especially 30x) of WGS is likely to how to get zithromax z pak miss at least some coding variants as compared with whole-exome sequencing (WES, especially >100x).View this table:Table 1 Technologies and study designs for detecting rare variantsThere are some lower-cost alternatives as well. First, a combination of low-depth WGS and imputation is another choice.

Imputation is a statistical method that can determine genotypes that are not how to get zithromax z pak directly detected by taking advantage of various previously sequenced reference panels. For instance, Martínez-Bueno and Alarcón-Riquelme identified rare variants that were jointly associated with systemic lupus erythematosus (SLE) within 98 SLE candidate genes by applying genome-wide imputation and other techniques.27 Notably, some studies have indicated that the newer imputation panels, such as the recent Haplotype Reference Consortium panel and how to get zithromax z pak the combined UK10K and 1000 Genomes projects phase III, provide better quality of imputation for rare variants compared with early panel, such as the UK10K, which underlines the significance and potential of larger reference panels to impute rare variants.28 29 Nevertheless, the power of imputation for identifying rare variants is attenuated because its accuracy decreases with decreasing MAF. Additionally, studies have indicated that the utility of population-specific panels leads to improved imputation accuracy of rare variants.30 Therefore, the utilisation of imputation is relatively limited in non-European populations because of the lack of ethnicity-specific reference cohorts.Second, using WES finds rare variants within protein-coding regions. Given the reality that only an exceedingly small portion of the human genome is coding sequence and how to get zithromax z pak the functions of protein-coding variants are more easily interpreted, WES is considered a cost-effective technique for discovering rare variants. However, an obvious defect is that how to get zithromax z pak WES ignores non-coding regions, which account for 98% of the human genome.

Moreover, most loci identified by GWAS are located in non-coding regions, and evidence indicates that these regions play critical roles in complex disorders and have significant biological functions.31 32Third, targeted sequencing investigates a specific part of the genome, including candidate genes identified by previous studies and clinically significant genes. For instance, Rivas et al identified a protein-truncating variant of the gene RNF186 that can exert a protective effect against ulcerative colitis via changed localisation how to get zithromax z pak and decreased expression by conducting targeted sequencing in regions previously associated with inflammatory bowel disease. They found that this loss-of-function variant was a how to get zithromax z pak promising therapeutic target.33 However, some targeted sequencing studies have failed to detect rare risk variants, indicating the deficiency of this method in discovering rare and low-frequency variants.24 34In addition, burden tests, which collapse information for multiple variants into a single genetic score and analyse the association between the score and disease characteristic, are a common approach in genomics to potentialise identification of rare variants, because aggregating analysis of variants within a gene can improve the power to detect statistical signals between case and control subjects. For example, a study analysed WES data from 393 patients with idiopathic hypogonadotropic hypogonadism (IHH) against 123 136 control subjects from public sequencing database, and identified a significant burden in TYRO3, a candidate gene implicated in IHH in mouse models.35 However, this gene-based burden testing approach will lose power when effects of variants are not in the same direction or the causal variants only account for a small fraction.36Traditional genetic studies have focused mostly on DNA sequences collected from unrelated individuals. However, a variety of new study designs have been applied to finding rare variants with the goal of decreasing sample sizes and costs how to get zithromax z pak.

The common feature of these designs, including extreme phenotype sampling, population isolates and family studies (table 1), is that they improve the power of rare variant testing by selecting a specific population.37–39Challenges for identifying rare how to get zithromax z pak and low-frequency variantsThe detection and analysis of rare and low-frequency variants constitute a rising research field, but this field has encountered substantial obstacles and challenges. First, the statistical analysis of rare and low-frequency variants is far more complicated and difficult than the analysis of common variants. For example, because the number of rare variants is greater than the number of common variants, the significance threshold or p value established for GWAS is not appropriate for rare variant association studies.40 The linkage disequilibrium (LD) r2 between two rare variants or a common variant and a rare variant cannot be accurately calculated, and as such it is difficult to define if novel rare variants are independent from known rare or common variants.41 42 A variety of traditional methods used to reduce or eliminate confounding factors and population stratification, such as linear mixed effect models and principal components analysis, are not applicable to the analysis of rare and how to get zithromax z pak low-frequency variants because rare variants and the distribution of disease risk are strictly localised. A study indicates that the estimated ancestry scores can be used to control the population stratification if the how to get zithromax z pak pool of control is large. Also, off-targeted read might be applied for controlling population stratification in targeted sequencing.43 Moreover, because these variants are rare, the strategy used to analyse common variants, which is based on analysing a single variant at a time, is underpowered to detect rare variants and can do so only if the effect size or sample size is exceedingly large.44 Thus, alternative methods have been developed to analyse the aggregate effect of rare variants.45–47 These methods, such as burden tests, variance component test and exponential combination tests, evaluate association for multiple variants in a gene or a biologically region.

Combined analysis of genetic association data with other biological information, such as methylation, gene expression and biological pathways, can also leads to substantial gain In how to get zithromax z pak the statistical power of rare variants studies.48–50Second, it still remains challenging to apply genetic information obtained by rare variants association studies to diagnostic and prognostic medicine because some healthy individuals carry deleterious variants. For example, Flannick et al found that a large portion of the general population carries low-frequency non-synonymous mutations that can change the length or sequence of coding proteins in maturity-onset diabetes of young genes, and these carriers remain normoglycaemic through middle age.51 In addition, Bick et al discovered that rare variants in sarcomere protein genes could boost the risk of adverse cardiovascular events in Framingham Heart Study participants, and more surprisingly, a large number of non-synonymous variants, including nonsense, missense and splice variants, are present in healthy populations.52 Therefore, the functional validation of rare and low-frequency genetic variants is necessary to determine the causality in genotype-phenotype analysis.Third, many rare and low-frequency variants are geographically localised and population specific, so it is how to get zithromax z pak difficult to find suitable replication panels and generate a common population. Nelson et al sequenced 202 drug target genes in coding regions in 14 002 people and found that 95% of observed variants are rare and at least 74% are detected in only one or two individuals.53 Similarly, a study conducted in 2440 individuals of African and European ancestry found that 86% of over 500 000 variants identified are rare, and most are previously unknown.54 Notably, these studies indicate that the vast majority of rare variant allelic spectra are unique to their sample sets and need to be identified by direct resequencing.Finally, although some detection studies of rare and low-frequency variants, such as WES and data processing software, are relatively standardised, many aspects of this emerging field, including WES capture technologies and even the definition of rare variants, still do not have uniform standards. Therefore, combining data generated from different groups is problematic.Benefits of identifying rare and low-frequency variantsIt has been suggested that rare how to get zithromax z pak and low-frequency variants account for a large proportion of the genetic variation in the human genome represented by the 1000 Genomes Project.55 56 Although a substantial number of SNPs have been identified by GWAS, there is still a so-called ‘missing heritability’ phenomenon in complex disorders.57 For instance, GWAS have identified >80 common variants with small effect sizes for T2DM, which can explain only 10% of the total heritability.58 To address this issue, several hypotheses have been proposed, and great technological advances have provided a better understanding of the genetic architecture of common diseases over the past several years. Rare and how to get zithromax z pak low-frequency variants can influence both susceptibility to common complex diseases and their phenotypes (table 2).59–62 For example, researchers performed WGS in 1038 pulmonary arterial hypertension (PAH, a rare disorder characterised by occlusion of arterioles in the lung) cases and 6385 control subjects and make the total proportion of cases explained by mutations increased to 23.5% from previously established 19.9% by incorporating novel rare variants and genes identified.63 Also, a study indicated that rare variants of SLC22A12 gene influence urate reabsorption and the heritability explained by these SLC22A12 variants exceeds 10%, indicating that rare functional variants make substantial contribution to the ‘missing heritability’ of serum urate level.64 In fact, a ‘common disease-rare variant model’ that assumes rare variants with high penetrance may be involved in increased complex disease risk has been proposed.59 65 It is obvious that great genetic heterogeneity exists under this model.

Intriguingly, in line with this model, some autoimmune diseases, such as T1DM, are extremely heterogeneous.View this table:Table 2 Rare and low-frequency variants associated with T1DM, T2DM and other autoimmune diseasesBesides rare and low-frequency genetic variants, there are some other hypotheses to explain the ‘missing heritability’.59 For example, empirical and theoretical analyses have indicated that multiple genetic variants with small effects are missed because GWAS are underpowered to capture these variants, therefore, taking into account genetic variants with smaller effects that do not reach significance will contribute to disease susceptibility and phenotype variability. Additionally, structural variants, such as CNV, are poorly studied owing to insufficient coverage on SNP chips.66 The presence how to get zithromax z pak of gene-gene (epistasis) and gene-environmental interactions may also contribute to the ‘missing heritability’.67In addition, the candidate regions identified by GWAS sometimes harbour several different genes. Identifying rare genetic variants is helpful to pinpoint causal genes within the loci identified by GWAS.68 Moreover, the identification of rare and low-frequency variants may result in the identification of new candidate genes.40 For instance, researchers identified a heterozygote truncating mutation within CLCN1 gene by performing WES in patients with statin-associated myopathy and therefore, determined a novel candidate gene of this disease.69 Additionally, it has been suggested that rare variants are likely to have appeared more recently than common variants, leading to reduced LD and making them more easily interpretable than common variants.21Moreover, how to get zithromax z pak early studies have indicated that rare and low-frequency genetic variants may have larger effects on complex disease phenotypes and susceptibility than common variants.70 Therefore, it is helpful to reveal the genetic pathways underlying diseases and to provide clinically actionable targets for personalised medicine. As an example, Roth et al found that rare and low-frequency genetic variants with large phenotypic effects within the proprotein convertase subtilisin/kexin 9 (PCSK9) gene, which encodes products that bind to the low-density lipoprotein (LDL) receptor and increase its degradation, can lower the risk of coronary heart disease (CHD) by reducing the circulating level of LDL cholesterol.71 Based on this research, a fully human monoclonal antibody targeting PCSK9 has been proven to increase LDL receptor recycling and decrease LDL cholesterol level.72 These findings provide a new treatment and prevention strategy for hypercholesterolaemia and CHD and offer inspiration for the transformation of genetic discoveries into clinical practice.Rare and low-frequency variants and T1DMFocusing on autoimmune diabetes, fully understanding the genetic factors underlying T1DM is beneficial for revealing its pathophysiology, discovering new drug targets and developing predictive and personalised medicine (figure 2). It is especially vital and valuable how to get zithromax z pak because T1DM is extremely complex and heterogeneous.

The candidate T1DM loci identified by GWAS sometimes contain several distinct genes, and strong how to get zithromax z pak LD makes it difficult to pinpoint the precise causative genes in genomic regions. In addition, the fact that many SNPs reside in non-coding regions or do not have obvious functional effects offers few clues to ascertain the causative genes. However, the discovery of rare and low-frequency disease-associated variants is helpful how to get zithromax z pak for T1DM candidate gene identification. The T1DM-associated region on human chromosome 2q24 harbours interferon (IFN) induced with helicase C domain 1 (IFIH1), GCA, FAP and part of how to get zithromax z pak KCNH7. The interaction between IFIH1 and double-stranded RNA, a byproduct of viral replication, leads to the secretion of IFNs.

While IFIH1 is a plausible susceptibility gene on the basis of its biological function, there is no direct evidence to indicate which of these genes in this locus how to get zithromax z pak is responsible for increased T1DM risk. Nejentsev et al resequenced the exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls how to get zithromax z pak and discovered 4 rare or low-frequency variants (OR=0.51–0.74, MAF <3%) with low LD within IFIH1 that could change the structure or expression of its product, melanoma differentiation-associated protein 5 and protect against T1DM.23 This finding suggests that IFIH1 is the disease-causing gene. Moreover, Ge et al found several rare deleterious variants, including two novel frameshift mutations (ss538819444 and ss37186329) and two missense mutations (rs74163663 and rs56048322) within PTPN22 by deeply sequencing the protein-coding regions of 301 genes in 49 loci previously identified by GWAS in 70 T1DM cases of European ancestry.22 This finding further confirmed that PTPN22 is a T1DM candidate gene on chromosome 1p13.2. Subsequent genotyping in 3609 families with T1DM indicated rs56048322 (MAF=0.87%), which leads to the production of two alternative PTPN22 transcripts and a novel isoform of its encoding protein, LYP, through affecting splicing of PTPN22, was significantly associated with T1DM independent of T1DM-associated common variant how to get zithromax z pak rs2476601. Functional analysis showed this isoform of LYP can cause hyporesponsiveness of CD4+ T cell how to get zithromax z pak to antigen stimulation in patients with T1DM.50 candidate loci have been identified by genome-wide association study.

The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants are likely to have more practical value in the treatment of T1DM because their ORs are larger how to get zithromax z pak than those of common variants. However, as the study of rare buy zithromax online ireland and low-frequency variants is an emerging research field, some hypotheses are still controversial and need how to get zithromax z pak further investigation. LD, linkage disequilibrium. MAF.

Minor allele frequency." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1569214299" data-figure-caption="The development of type 1 diabetes mellitus (T1DM). T1DM is caused by interplay between genetic and environmental factors, and epigenetics serves as a bridge between the two. To date, >50 candidate loci have been identified by genome-wide association study. The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants are likely to have more practical value in the treatment of T1DM because their ORs are larger than those of common variants.

However, as the study of rare and low-frequency variants is an emerging research field, some hypotheses are still controversial and need further investigation. LD, linkage disequilibrium. MAF. Minor allele frequency." data-icon-position data-hide-link-title="0">Figure 2 The development of type 1 diabetes mellitus (T1DM). T1DM is caused by interplay between genetic and environmental factors, and epigenetics serves as a bridge between the two.

To date, >50 candidate loci have been identified by genome-wide association study. The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants are likely to have more practical value in the treatment of T1DM because their ORs are larger than those of common variants. However, as the study of rare and low-frequency variants is an emerging research field, some hypotheses are still controversial and need further investigation. LD, linkage disequilibrium.

MAF. Minor allele frequency.Additionally, as mentioned above, most variants that confer T1DM risk are common and have modest effects, limiting the clinical application of their discovery. However, some research has suggested that rare and low-frequency variants might have larger effect sizes than common variants. Theoretically, if a disorder affects reproduction, such as an autoimmune disease with early onset, genetic variants with strong effects will be maintained at a relatively low frequency through negative selection.21 Forgetta et al applied deep imputation of genotyped data in 9358 patients with T1DM and 15 705 controls from European cohorts to identify novel rare and low-frequency variants with large effect sizes on T1DM risk.13 Three novel rare and low-frequency variants, including rs192324744 in LDL receptor-related protein 1B (LRP1B, MAF=1.3%, OR=1.63), rs60587303 in serine threonine kinase 39 (STK39, MAF=0.5%, OR=1.97) and the intergenic variant rs2128344 (MAF=0.55%, OR=2.12), were found and validated by subsequent de novo genotyping.13 Notably, the effects of these SNPs (ORs ≥1.5) are comparable to those of the lead variants in INS and PTPN22. In vitro experiments indicated that STK39 is involved in T cell activation and effector functions and that inhibition of Stk39 can augment the inflammatory response by enhancing interleukin (IL)-2 signalling.

Therefore, STK39 may be a promising clinical intervention target.13Besides, previous study through fine mapping of known T1DM susceptible loci has identified a low-frequency variant rs34536443 (MAF=4%, OR=0.67) within tyrosine kinase 2 (TYK2) and a rare variant rs41295121 (MAF=1%, OR=0.49) within RNA binding motif protein 17 (RBM17, in the same locus as IL2RA).20 TYK2, belonging to Janus kinase (JAK) family, is associated with regulation of type I IFN signalling pathway. Some studies have demonstrated that rs34530443 plays protective roles in multiple autoimmune disorders and the underlying mechanisms might lie in the diminishment of IL-12, IL-23 and type I IFN signalling.73 The specific function of rs41295121 in context of autoimmunity and T1DM needs further investigation.As for some practical issues such as sample sizes and high costs, a study indicated that a well-powered rare variant association study should include discovery sets with at least 25 000 cases and a substantial replication set.44 There are some alternative methods to decrease the sample sizes or costs in the context of T1DM. For example, combined analysis of rare variants within a T1DM-associated gene or region can lead to substantial reduction of required sample sizes. In addition, preferential selection of individuals with extreme phenotype on the basis of known risk factors, including age of disease onset, family history of diabetes and diabetic auto-antibodies, can also improve the association power because rare variants might be enriched among them.74Overall, among the identified T1DM loci, the candidate genes with rare or low-frequency variants include TYK2, IFIH1, RBM17, PTPN22, STK39 and LRP1B.13 20 22 23 Many unidentified variants may remain to be dissected, because studies focused on other diseases suggest that rare and low-frequency variants account for the majority of all variants.27 75ConclusionDriven by advancements in sequencing technologies, there has been great improvement in the identification of rare and low-frequency variants that cause complex human diseases, such as T1DM. The benefits of this field can be stated as follows.

(1) characterisation of rare and low-frequency variants may lead to a full understanding of the genetic component of this disorder. (2) detection of rare and low-frequency variants can pinpoint the genes that are actually responsible for increased T1DM risk within the loci identified by GWAS. (3) some new candidate genes for T1DM can be found due to enhanced power to discover rare variants. (4) rare and low-frequency variants are expected to make a significant contribution to human phenotypes and disease susceptibility because some studies indicate the majority of protein-coding variants tend to be evolutionarily recent and rare54. (5) accumulated evidence indicates that rare and low-frequency variants have larger phenotypic effects than common variants, suggesting that they will offer more actionable clinical targets and hold tremendous promise in predictive and personalised medicine.However, some issues remain to be addressed.

First, controversy persists about the importance of rare and low-frequency variants in common diseases. Encouragingly, recent studies have found that some such variants, such as rs60587303 in STK39, indeed have larger effect sizes than common variants in the pathogenesis of T1DM. Second, the candidate genes for T1DM that have rare or low-frequency variants included only TYK2, RBM17, IFIH1, PTPN22, STK39 and LRP1B, which means there may still be many unidentified variants. Moreover, most studies in this field have examined European populations. However, rare and low-frequency variants are geographically localised and population specific.

In particular, the heritable background of T1DM varies among different ethnic groups. These facts will limit the practical application of rare and low-frequency variants.In conclusion, the identification of rare and low-frequency genetic variants will provide new insights into the pathophysiology of T1DM and offer new potential drug targets in the post-GWAS era, despite the many challenges and uncertainties remaining in this field.AbstractAccurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation of cancer risk and management of patients. Consistency in the weighting assigned to individual elements of evidence has been much improved by the American College of Medical Genetics (ACMG) 2015 framework for variant classification, UK Association for Clinical Genomic Science (UK-ACGS) Best Practice Guidelines and subsequent Cancer Variant Interpretation Group UK (CanVIG-UK) consensus specification for CSGs. However, considerable inconsistency persists regarding practice in the combination of evidence elements. CanVIG-UK is a national subspecialist multidisciplinary network for cancer susceptibility genomic variant interpretation, comprising clinical scientist and clinical geneticist representation from each of the 25 diagnostic laboratories/clinical genetic units across the UK and Republic of Ireland.

Here, we summarise the aggregated evidence elements and combinations possible within different variant classification schemata currently employed for CSGs (ACMG, UK-ACGS, CanVIG-UK and ClinGen gene-specific guidance for PTEN, TP53 and CDH1). We present consensus recommendations from CanVIG-UK regarding (1) consistent scoring for combinations of evidence elements using a validated numerical ‘exponent score’ (2) new combinations of evidence elements constituting likely pathogenic’ and ‘pathogenic’ classification categories, (3) which evidence elements can and cannot be used in combination for specific variant types and (4) classification of variants for which there are evidence elements for both pathogenicity and benignity.geneticsgenomicsgenetic testinggeneticsmedicalgenetic variationhttps://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See. Https://creativecommons.org/licenses/by/4.0/..

IntroductionCurrently, type 1 diabetes mellitus (T1DM) is defined as an autoimmune disorder classically characterised by pancreatic islet beta-cell destruction triggered by autoreactive T cells, resulting in subsequent severe insulin deficiency low price zithromax and lifelong reliance on exogenous insulin.1 2 This autoimmune diabetes accounts for 5%–19% of diabetes and represents the main form of diabetes in children and adolescents.3 Its incidence is increasing worldwide at http://djmobileservices.com/?p=76 a rate of 2%–5% per year.4 This rising incidence and multiple severe diabetic complications lead to increased mortality and morbidity and aggravate the economic burden of the disease. It is accepted that the interplay between genetic factors and environmental precipitators, including ancestry and geographic location, viral and bacterial s, vitamin D, hygiene and microbiota, leads to specific tissue inflammation, namely, insulitis, insulin-producing cell death and consequent clinical disease.5–9The genetic component of T1DM can be demonstrated by the fact that siblings and offspring of patients with T1DM have a higher risk than the general population, and disease concordance in identical twins is higher than that in dizygotic twins.10 11 Over the past few years, genome-wide association study (GWAS), which measures and analyses a million or more DNA sequence variations in known linkage regions in unrelated individuals, have identified at least 58 susceptible loci combined with linkage analysis and candidate gene studies (figure 1).12–14 Most of the identified variants are common (minor allele frequency (MAF) >5%) and have modest effects (OR <1.5), although the effects of susceptibility genes such as human leucocyte antigen (HLA), insulin (INS) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) are stronger (figure 1).13 The HLA region (OR >6), located on human chromosome 6p21 and identified by linkage analysis, accounts for the largest proportion of T1DM heritability and explains approximately low price zithromax 50% of genetic T1DM risk.15 In addition to HLA, variants within the INS and PTPN22 loci, which were first identified by candidate gene studies, have larger effect sizes (OR >2) than other variants.13 The INS gene on human chromosome 11p15.5 offers the next strongest genetic risk association with T1DM after HLA and accounts for approximately 10% of genetic susceptibility to T1DM.16 It is believed that ‘missing heritability’ can be at least partially elucidated by rare and low-frequency variants (rare variants defined as variants with MAF ≤1% and low-frequency variants defined as variants with MAF=1%–5%), and some findings have indicated that rare variants have larger effect sizes than common variants.17–19 From an evolutionary standpoint, risk variants with higher penetrance are more likely to be rare due to negative selection. Taking an extreme example, monogenic/Mendelian disorders such as autoimmune polyendocrinopathy syndrome type I are caused by rare variants with large effect sizes and low price zithromax high penetrance. Intriguingly, recent and previous studies focusing on the identification of rare and low-frequency variants involved in T1DM have found a handful of such variants, and some of them do have large effect sizes.13 20–23Candidate genes or loci of type 1 diabetes mellitus (T1DM) and their ORs (the yellow bars represent the rare and low-frequency genetic variants of T1DM).76–79 " data-icon-position data-hide-link-title="0">Figure 1 Candidate genes or loci of type 1 diabetes mellitus (T1DM) and their ORs (the yellow bars represent the rare and low-frequency genetic variants of T1DM).76–79However, some studies suggest that most rare variants have only small or modest effects.24 Therefore, it remains to be seen whether the tendency of rare and low-frequency variants to have large effects is a universal phenomenon.

Even though its practical value in clinical medicine may be restricted if the hypothesis that most rare variants have only a small effect is true, low price zithromax there is still intrinsic value in this field. Such studies can lead to the discovery low price zithromax of new candidate genes implicated in disorders or human phenotypes25 and determine causal genes in candidate regions identified by GWAS. Other than understanding better its pathophysiology, new loci could lead to the identification of new biomarkers or represent drug targets for T1DM.Identifying rare and low-frequency variantsRecently, advances in next-generation DNA sequencing technologies as well as bioinformatic tools and methods to process and analyse the resulting data have enhanced the ability of researchers to find rare variants, and the decreasing cost of these technologies has made it feasible to apply them to related studies (table 1).26 The most comprehensive approach is high-depth whole-genome sequencing (WGS) due to its excellent coverage. However, high costs and low price zithromax multiple computational challenges have restricted its application.21 In addition to WGS with high or low depth, SNP-array genome-wide genotyping and imputation has been used to identify rare variants.

Notably, current sequencing depth (especially 30x) of WGS is likely to miss at least some coding variants as compared with whole-exome sequencing (WES, especially >100x).View this table:Table 1 Technologies and study designs for detecting rare variantsThere are some low price zithromax lower-cost alternatives as well. First, a combination of low-depth WGS and imputation is another choice. Imputation is a statistical method that low price zithromax can determine genotypes that are not directly detected by taking advantage of various previously sequenced reference panels. For instance, Martínez-Bueno and Alarcón-Riquelme identified rare variants that were jointly associated with systemic lupus erythematosus (SLE) within 98 SLE candidate genes by applying genome-wide imputation and other techniques.27 Notably, some studies have indicated that the newer imputation panels, such as the recent Haplotype Reference Consortium panel and the combined UK10K and 1000 Genomes projects phase III, provide better quality of imputation for rare variants compared with early panel, such as the UK10K, which underlines the significance and potential of larger reference panels to impute rare variants.28 29 Nevertheless, the power of imputation for identifying rare variants is attenuated because its accuracy decreases low price zithromax with decreasing MAF.

Additionally, studies have indicated that the utility of population-specific panels leads to improved imputation accuracy of rare variants.30 Therefore, the utilisation of imputation is relatively limited in non-European populations because of the lack of ethnicity-specific reference cohorts.Second, using WES finds rare variants within protein-coding regions. Given the reality that only an exceedingly small portion of the low price zithromax human genome is coding sequence and the functions of protein-coding variants are more easily interpreted, WES is considered a cost-effective technique for discovering rare variants. However, an obvious defect is low price zithromax that WES ignores non-coding regions, which account for 98% of the human genome. Moreover, most loci identified by GWAS are located in non-coding regions, and evidence indicates that these regions play critical roles in complex disorders and have significant biological functions.31 32Third, targeted sequencing investigates a specific part of the genome, including candidate genes identified by previous studies and clinically significant genes.

For instance, Rivas et al identified a protein-truncating variant of the gene RNF186 that can exert a protective effect against ulcerative colitis via changed localisation and decreased expression by conducting targeted sequencing in regions previously associated with inflammatory low price zithromax bowel disease. They found that this loss-of-function variant was a promising therapeutic target.33 However, some targeted sequencing studies have failed to detect rare risk variants, indicating the deficiency of this method in discovering rare and low-frequency variants.24 34In addition, burden tests, which collapse information for multiple variants into a single genetic score and analyse the association between the score and disease characteristic, are a common approach in genomics to potentialise identification of rare variants, because aggregating analysis of variants within low price zithromax a gene can improve the power to detect statistical signals between case and control subjects. For example, a study analysed WES data from 393 patients with idiopathic hypogonadotropic hypogonadism (IHH) against 123 136 control subjects from public sequencing database, and identified a significant burden in TYRO3, a candidate gene implicated in IHH in mouse models.35 However, this gene-based burden testing approach will lose power when effects of variants are not in the same direction or the causal variants only account for a small fraction.36Traditional genetic studies have focused mostly on DNA sequences collected from unrelated individuals. However, a variety of low price zithromax new study designs have been applied to finding rare variants with the goal of decreasing sample sizes and costs.

The common feature of these designs, including extreme phenotype sampling, population isolates and family studies (table 1), is that they improve the power of rare variant testing by selecting low price zithromax a specific population.37–39Challenges for identifying rare and low-frequency variantsThe detection and analysis of rare and low-frequency variants constitute a rising research field, but this field has encountered substantial obstacles and challenges. First, the statistical analysis of rare and low-frequency variants is far more complicated and difficult than the analysis of common variants. For example, because the number of rare variants is greater than the number of common variants, the significance threshold or p value established for GWAS is not appropriate for rare variant association studies.40 The linkage disequilibrium (LD) r2 between two rare variants or a common variant and low price zithromax a rare variant cannot be accurately calculated, and as such it is difficult to define if novel rare variants are independent from known rare or common variants.41 42 A variety of traditional methods used to reduce or eliminate confounding factors and population stratification, such as linear mixed effect models and principal components analysis, are not applicable to the analysis of rare and low-frequency variants because rare variants and the distribution of disease risk are strictly localised. A study indicates low price zithromax that the estimated ancestry scores can be used to control the population stratification if the pool of control is large.

Also, off-targeted read might be applied for controlling population stratification in targeted sequencing.43 Moreover, because these variants are rare, the strategy used to analyse common variants, which is based on analysing a single variant at a time, is underpowered to detect rare variants and can do so only if the effect size or sample size is exceedingly large.44 Thus, alternative methods have been developed to analyse the aggregate effect of rare variants.45–47 These methods, such as burden tests, variance component test and exponential combination tests, evaluate association for multiple variants in a gene or a biologically region. Combined analysis of genetic association data with other biological information, such as methylation, gene expression and biological pathways, can also leads to low price zithromax substantial gain In the statistical power of rare variants studies.48–50Second, it still remains challenging to apply genetic information obtained by rare variants association studies to diagnostic and prognostic medicine because some healthy individuals carry deleterious variants. For example, Flannick et al found that a large portion of the general population carries low-frequency non-synonymous mutations that can change the length or sequence of coding proteins in maturity-onset diabetes of young genes, and these carriers remain normoglycaemic through middle age.51 In addition, Bick et al discovered that rare variants in sarcomere protein genes could boost the risk of adverse cardiovascular events in low price zithromax Framingham Heart Study participants, and more surprisingly, a large number of non-synonymous variants, including nonsense, missense and splice variants, are present in healthy populations.52 Therefore, the functional validation of rare and low-frequency genetic variants is necessary to determine the causality in genotype-phenotype analysis.Third, many rare and low-frequency variants are geographically localised and population specific, so it is difficult to find suitable replication panels and generate a common population. Nelson et al sequenced 202 drug target genes in coding regions in 14 002 people and found that 95% of observed variants are rare and at least 74% are detected in only one or two individuals.53 Similarly, a study conducted in 2440 individuals of African and European ancestry found that 86% of over 500 000 variants identified are rare, and most are previously unknown.54 Notably, these studies indicate that the vast majority of rare variant allelic spectra are unique to their sample sets and need to be identified by direct resequencing.Finally, although some detection studies of rare and low-frequency variants, such as WES and data processing software, are relatively standardised, many aspects of this emerging field, including WES capture technologies and even the definition of rare variants, still do not have uniform standards.

Therefore, combining data generated from different groups is problematic.Benefits of identifying rare and low-frequency variantsIt has been suggested that rare and low-frequency variants account for a large proportion of the genetic variation in the human genome represented by the 1000 Genomes Project.55 56 Although a low price zithromax substantial number of SNPs have been identified by GWAS, there is still a so-called ‘missing heritability’ phenomenon in complex disorders.57 For instance, GWAS have identified >80 common variants with small effect sizes for T2DM, which can explain only 10% of the total heritability.58 To address this issue, several hypotheses have been proposed, and great technological advances have provided a better understanding of the genetic architecture of common diseases over the past several years. Rare and low-frequency variants can influence both susceptibility to common complex diseases and their phenotypes (table 2).59–62 For example, researchers performed WGS in 1038 pulmonary arterial hypertension (PAH, a rare disorder characterised by occlusion of arterioles in the lung) cases and 6385 control subjects and make the total proportion of cases explained by mutations increased to 23.5% from previously established 19.9% by incorporating novel rare variants and genes identified.63 Also, a study indicated low price zithromax that rare variants of SLC22A12 gene influence urate reabsorption and the heritability explained by these SLC22A12 variants exceeds 10%, indicating that rare functional variants make substantial contribution to the ‘missing heritability’ of serum urate level.64 In fact, a ‘common disease-rare variant model’ that assumes rare variants with high penetrance may be involved in increased complex disease risk has been proposed.59 65 It is obvious that great genetic heterogeneity exists under this model. Intriguingly, in line with this model, some autoimmune diseases, such as T1DM, are extremely heterogeneous.View this table:Table 2 Rare and low-frequency variants associated with T1DM, T2DM and other autoimmune diseasesBesides rare and low-frequency genetic variants, there are some other hypotheses to explain the ‘missing heritability’.59 For example, empirical and theoretical analyses have indicated that multiple genetic variants with small effects are missed because GWAS are underpowered to capture these variants, therefore, taking into account genetic variants with smaller effects that do not reach significance will contribute to disease susceptibility and phenotype variability. Additionally, structural variants, such as CNV, are poorly studied owing to insufficient coverage on SNP chips.66 The presence of gene-gene low price zithromax (epistasis) and gene-environmental interactions may also contribute to the ‘missing heritability’.67In addition, the candidate regions identified by GWAS sometimes harbour several different genes.

Identifying rare genetic variants is helpful to pinpoint causal genes within the loci identified by GWAS.68 Moreover, the identification of rare and low-frequency variants may result in the identification of new candidate genes.40 For instance, researchers identified a heterozygote truncating mutation within CLCN1 gene by performing WES in patients with statin-associated myopathy and therefore, determined a novel candidate gene of this disease.69 Additionally, it has been suggested that rare variants are likely to have appeared more recently than common variants, leading to reduced LD and making them more easily interpretable than common variants.21Moreover, early studies have indicated that rare and low-frequency low price zithromax genetic variants may have larger effects on complex disease phenotypes and susceptibility than common variants.70 Therefore, it is helpful to reveal the genetic pathways underlying diseases and to provide clinically actionable targets for personalised medicine. As an example, Roth et al found that rare and low-frequency genetic variants with large phenotypic effects within the proprotein convertase subtilisin/kexin 9 (PCSK9) gene, which encodes products that bind to the low-density lipoprotein (LDL) receptor and increase its degradation, can lower the risk of coronary heart disease (CHD) by reducing the circulating level of LDL cholesterol.71 Based on this research, a fully human monoclonal antibody targeting PCSK9 has been proven to increase LDL receptor recycling and decrease LDL cholesterol level.72 These findings provide a new treatment and prevention strategy for hypercholesterolaemia and CHD and offer inspiration for the transformation of genetic discoveries into clinical practice.Rare and low-frequency variants and T1DMFocusing on autoimmune diabetes, fully understanding the genetic factors underlying T1DM is beneficial for revealing its pathophysiology, discovering new drug targets and developing predictive and personalised medicine (figure 2). It is especially vital and valuable because T1DM is extremely low price zithromax complex and heterogeneous. The candidate T1DM low price zithromax loci identified by GWAS sometimes contain several distinct genes, and strong LD makes it difficult to pinpoint the precise causative genes in genomic regions.

In addition, the fact that many SNPs reside in non-coding regions or do not have obvious functional effects offers few clues to ascertain the causative genes. However, the discovery of rare and low-frequency disease-associated variants is helpful low price zithromax for T1DM candidate gene identification. The T1DM-associated region on human chromosome 2q24 harbours interferon (IFN) induced with helicase C domain low price zithromax 1 (IFIH1), GCA, FAP and part of KCNH7. The interaction between IFIH1 and double-stranded RNA, a byproduct of viral replication, leads to the secretion of IFNs.

While IFIH1 is a plausible susceptibility gene on the basis of its biological function, there is no direct evidence to indicate which of these genes in this locus is responsible for increased low price zithromax T1DM risk. Nejentsev et al resequenced the exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls and discovered 4 rare or low-frequency variants (OR=0.51–0.74, MAF <3%) with low LD within IFIH1 that could change the structure or expression low price zithromax of its product, melanoma differentiation-associated protein 5 and protect against T1DM.23 This finding suggests that IFIH1 is the disease-causing gene. Moreover, Ge et al found several rare deleterious variants, including two novel frameshift mutations (ss538819444 and ss37186329) and two missense mutations (rs74163663 and rs56048322) within PTPN22 by deeply sequencing the protein-coding regions of 301 genes in 49 loci previously identified by GWAS in 70 T1DM cases of European ancestry.22 This finding further confirmed that PTPN22 is a T1DM candidate gene on chromosome 1p13.2. Subsequent genotyping in 3609 families with T1DM indicated rs56048322 (MAF=0.87%), which leads to the production of two alternative PTPN22 transcripts and a novel isoform of its encoding protein, LYP, through affecting splicing of PTPN22, was significantly associated low price zithromax with T1DM independent of T1DM-associated common variant rs2476601.

Functional analysis showed this low price zithromax isoform of LYP can cause hyporesponsiveness of CD4+ T cell to antigen stimulation in patients with T1DM.50 candidate loci have been identified by genome-wide association study. The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants low price zithromax are likely to have more practical value in the treatment of T1DM because their ORs are larger than those of common variants. However, as the study of rare and low-frequency variants is an emerging low price zithromax research field, some hypotheses are still controversial and need further investigation.

LD, linkage disequilibrium. MAF. Minor allele frequency." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1569214299" data-figure-caption="The development of type 1 diabetes mellitus (T1DM). T1DM is caused by interplay between genetic and environmental factors, and epigenetics serves as a bridge between the two.

To date, >50 candidate loci have been identified by genome-wide association study. The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants are likely to have more practical value in the treatment of T1DM because their ORs are larger than those of common variants. However, as the study of rare and low-frequency variants is an emerging research field, some hypotheses are still controversial and need further investigation.

LD, linkage disequilibrium. MAF. Minor allele frequency." data-icon-position data-hide-link-title="0">Figure 2 The development of type 1 diabetes mellitus (T1DM). T1DM is caused by interplay between genetic and environmental factors, and epigenetics serves as a bridge between the two.

To date, >50 candidate loci have been identified by genome-wide association study. The genetic variants within these risk regions can be divided into common variants, low-frequency variants and rare variants according to their different minor allele frequencies. The rare and low-frequency variants are likely to have more practical value in the treatment of T1DM because their ORs are larger than those of common variants. However, as the study of rare and low-frequency variants is an emerging research field, some hypotheses are still controversial and need further investigation.

LD, linkage disequilibrium. MAF. Minor allele frequency.Additionally, as mentioned above, most variants that confer T1DM risk are common and have modest effects, limiting the clinical application of their discovery. However, some research has suggested that rare and low-frequency variants might have larger effect sizes than common variants.

Theoretically, if a disorder affects reproduction, such as an autoimmune disease with early onset, genetic variants with strong effects will be maintained at a relatively low frequency through negative selection.21 Forgetta et al applied deep imputation of genotyped data in 9358 patients with T1DM and 15 705 controls from European cohorts to identify novel rare and low-frequency variants with large effect sizes on T1DM risk.13 Three novel rare and low-frequency variants, including rs192324744 in LDL receptor-related protein 1B (LRP1B, MAF=1.3%, OR=1.63), rs60587303 in serine threonine kinase 39 (STK39, MAF=0.5%, OR=1.97) and the intergenic variant rs2128344 (MAF=0.55%, OR=2.12), were found and validated by subsequent de novo genotyping.13 Notably, the effects of these SNPs (ORs ≥1.5) are comparable to those of the lead variants in INS and PTPN22. In vitro experiments indicated that STK39 is involved in T cell activation and effector functions and that inhibition of Stk39 can augment the inflammatory response by enhancing interleukin (IL)-2 signalling. Therefore, STK39 may be a promising clinical intervention target.13Besides, previous study through fine mapping of known T1DM susceptible loci has identified a low-frequency variant rs34536443 (MAF=4%, OR=0.67) within tyrosine kinase 2 (TYK2) and a rare variant rs41295121 (MAF=1%, OR=0.49) within RNA binding motif protein 17 (RBM17, in the same locus as IL2RA).20 TYK2, belonging to Janus kinase (JAK) family, is associated with regulation of type I IFN signalling pathway. Some studies have demonstrated that rs34530443 plays protective roles in multiple autoimmune disorders and the underlying mechanisms might lie in the diminishment of IL-12, IL-23 and type I IFN signalling.73 The specific function of rs41295121 in context of autoimmunity and T1DM needs further investigation.As for some practical issues such as sample sizes and high costs, a study indicated that a well-powered rare variant association study should include discovery sets with at least 25 000 cases and a substantial replication set.44 There are some alternative methods to decrease the sample sizes or costs in the context of T1DM.

For example, combined analysis of rare variants within a T1DM-associated gene or region can lead to substantial reduction of required sample sizes. In addition, preferential selection of individuals with extreme phenotype on the basis of known risk factors, including age of disease onset, family history of diabetes and diabetic auto-antibodies, can also improve the association power because rare variants might be enriched among them.74Overall, among the identified T1DM loci, the candidate genes with rare or low-frequency variants include TYK2, IFIH1, RBM17, PTPN22, STK39 and LRP1B.13 20 22 23 Many unidentified variants may remain to be dissected, because studies focused on other diseases suggest that rare and low-frequency variants account for the majority of all variants.27 75ConclusionDriven by advancements in sequencing technologies, there has been great improvement in the identification of rare and low-frequency variants that cause complex human diseases, such as T1DM. The benefits of this field can be stated as follows. (1) characterisation of rare and low-frequency variants may lead to a full understanding of the genetic component of this disorder.

(2) detection of rare and low-frequency variants can pinpoint the genes that are actually responsible for increased T1DM risk within the loci identified by GWAS. (3) some new candidate genes for T1DM can be found due to enhanced power to discover rare variants. (4) rare and low-frequency variants are expected to make a significant contribution to human phenotypes and disease susceptibility because some studies indicate the majority of protein-coding variants tend to be evolutionarily recent and rare54. (5) accumulated evidence indicates that rare and low-frequency variants have larger phenotypic effects than common variants, suggesting that they will offer more actionable clinical targets and hold tremendous promise in predictive and personalised medicine.However, some issues remain to be addressed.

First, controversy persists about the importance of rare and low-frequency variants in common diseases. Encouragingly, recent studies have found that some such variants, such as rs60587303 in STK39, indeed have larger effect sizes than common variants in the pathogenesis of T1DM. Second, the candidate genes for T1DM that have rare or low-frequency variants included only TYK2, RBM17, IFIH1, PTPN22, STK39 and LRP1B, which means there may still be many unidentified variants. Moreover, most studies in this field have examined European populations.

However, rare and low-frequency variants are geographically localised and population specific. In particular, the heritable background of T1DM varies among different ethnic groups. These facts will limit the practical application of rare and low-frequency variants.In conclusion, the identification of rare and low-frequency genetic variants will provide new insights into the pathophysiology of T1DM and offer new potential drug targets in the post-GWAS era, despite the many challenges and uncertainties remaining in this field.AbstractAccurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation of cancer risk and management of patients. Consistency in the weighting assigned to individual elements of evidence has been much improved by the American College of Medical Genetics (ACMG) 2015 framework for variant classification, UK Association for Clinical Genomic Science (UK-ACGS) Best Practice Guidelines and subsequent Cancer Variant Interpretation Group UK (CanVIG-UK) consensus specification for CSGs.

However, considerable inconsistency persists regarding practice in the combination of evidence elements. CanVIG-UK is a national subspecialist multidisciplinary network for cancer susceptibility genomic variant interpretation, comprising clinical scientist and clinical geneticist representation from each of the 25 diagnostic laboratories/clinical genetic units across the UK and Republic of Ireland. Here, we summarise the aggregated evidence elements and combinations possible within different variant classification schemata currently employed for CSGs (ACMG, UK-ACGS, CanVIG-UK and ClinGen gene-specific guidance for PTEN, TP53 and CDH1). We present consensus recommendations from CanVIG-UK regarding (1) consistent scoring for combinations of evidence elements using a validated numerical ‘exponent score’ (2) new combinations of evidence elements constituting likely pathogenic’ and ‘pathogenic’ classification categories, (3) which evidence elements can and cannot be used in combination for specific variant types and (4) classification of variants for which there are evidence elements for both pathogenicity and benignity.geneticsgenomicsgenetic testinggeneticsmedicalgenetic variationhttps://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made.

See. Https://creativecommons.org/licenses/by/4.0/..

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Shutterstock browse around this website Florida’s low price zithromax Department of Economic Opportunity will receive more than $833,000 from the U.S. Department of Labor to fund programs to combat opioid use, addiction, and overdose in three counties. Part of the National Health Emergency Dislocated Worker Grant program, the project will provide grant low price zithromax recipients with disaster-relief employment in jobs that address impacts of the opioid crisis, such as peer recovery navigators. Additionally, the project provides employment and training services to participants looking to start careers in addiction, treatment, and pain management healthcare professions.

Dislocated Worker Grants temporarily expand the capacity of dislocated worker programs at the low price zithromax state and local levels by providing funding assistance for jobs in response to any large and unexpected economic event that causes job losses. Because the U.S. Department of Health and Human Services declared the opioid crisis a national public health emergency low price zithromax In October of 2017, Florida was eligible to request grant funding. Earlier this year, the U.S.

DOL made up to $100 million in Dislocated Worker Grants available to states as a result of the buy antibiotics zithromax after HHS declared the zithromax a national public health emergency. In 2018, Florida’s Brevard, Manatee, and Sarasota counties received a grant for up to $2.5 million for Dislocated Worker Grants..

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Maximizing health can i drink alcohol with zithromax coverage for DAP clients. Before and after winning the case Outline prepared by Geoffrey Hale and Cathy Roberts - updated August 2012 This outline is intended to assist Disability Advocacy Program (DAP) advocates maximize health insurance coverage for clients they are representing on Social Security/SSI disability determinations. We begin with a discussion of coverage options available while your client’s DAP case is pending and then outline the effect winning the DAP case can i drink alcohol with zithromax can have on your client’s access to health care coverage.

How your client is affected will vary depending on the source and amount of disability income he or she receives after the successful appeal. I. BACKGROUND can i drink alcohol with zithromax.

Public health coverage for your clients will primarily be provided by Medicaid and Medicare. The two programs are structured differently can i drink alcohol with zithromax and have different eligibility criteria, but in order to provide the most complete coverage possible for your clients, they must work effectively together. Understanding their interactions is essential to ensuring benefits for your client.

Here is a brief overview of the programs we will cover. A. Medicaid.

Medicaid is the public insurance program jointly funded by the federal, state and local governments for people of limited means. For federal Medicaid law, see 42 U.S.C. § 1396 et seq., 42 C.F.R.

§ 430 et seq. Regular Medicaid is described in New York’s State Plan and codified at N.Y. Soc.

18 N.Y.C.R.R. § 360, 505. New York also offers several additional programs to provide health care benefits to those whose income might be too high for Regular Medicaid.

i. Family Health Plus (FHPlus) is an extension of New York’s Medicaid program that provides health coverage for adults who are over-income for regular Medicaid. FHPlus is described in New York’s 1115 waiver and codified at N.Y.

§369-ee. ii. Child Health Plus (CHPlus) is a sliding scale premium program for children who are over-income for regular Medicaid.

Medicare is the federal health insurance program providing coverage for the elderly, disabled, and people with end-stage renal disease. Medicare is codified under title XVIII of the Social Security Law, see 42 U.S.C. § 1395 et seq., 42 C.F.R.

§ 400 et seq. Medicare is divided into four parts. i.

Part A covers hospital, skilled nursing facility, home health, and hospice care, with some deductibles and coinsurance. Most people are eligible for Part A at no cost. See 42 U.S.C.

ii. Part B provides medical insurance for doctor’s visits and other outpatient medical services. Medicare Part B has significant cost-sharing components.

There are monthly premiums (the standard premium in 2012 is $99.90. In addition, there is a $135 annual deductible (which will increase to $155 in 2010) as well as 20% co-insurance for most covered out-patient services. See 42 U.S.C.

iii. Part C, also called Medicare Advantage, provides traditional Medicare coverage (Parts A and B) through private managed care insurers. See 42 U.S.C.

Premium amounts for Medicare Advantage plans vary. Some Medicare Advantage plans include prescription drug coverage. iv.

Part D is an optional prescription drug benefit available to anyone with Medicare Parts A and B. See 42 U.S.C. § 1395w, 42 C.F.R.

§ 423.30(a)(1)(i) and (ii). Unlike Parts A and B, Part D benefits are provided directly through private plans offered by insurance companies. In order to receive prescription drug coverage, a Medicare beneficiary must join a Part D Plan or participate in a Medicare Advantage plan that provides prescription drug coverage.

C. Medicare Savings Programs (MSPs). Funded by the State Medicaid program, MSPs help eligible individuals meet some or all of their cost-sharing obligations under Medicare.

L. § 367-a(3)(a), (b), and (d). There are three separate MSPs, each with different eligibility requirements and providing different benefits.

i. Qualified Medicare Beneficiary (QMB). The QMB program provides the most comprehensive benefits.

Available to those with incomes at or below 100% of the Federal Poverty Level (FPL), the QMB program covers virtually all Medicare cost-sharing obligations. Part B premiums, Part A premiums, if there are any, and any and all deductibles and co-insurance. ii.

Special Low-Income Medicare Beneficiary (SLMB). For those with incomes between 100% and 120% FPL, the SLMB program will cover Part B premiums only. iii.

Qualified Individual (QI-1). For those with incomes between 120% and 135% FPL, but not otherwise Medicaid eligible, the QI-1 program covers Medicare Part B premiums. D.

Medicare Part D Low Income Subsidy (LIS or “Extra Help”). LIS is a federal subsidy administered by CMS that helps Medicare beneficiaries with limited income and/or resources pay for some or most of the costs of Medicare prescription drug coverage. See 42 C.F.R.

§ 423.773. Some of the costs covered in full or in part by LIS include the monthly premiums, annual deductible, co-payments, and the coverage gap. Individuals eligible for Medicaid, SSI, or MSP are deemed eligible for full LIS benefitsSee 42 C.F.R.

§ 423.773(c). LIS applications are treated as (“deemed”) applications for MSP benefits, See the Medicare Improvements for Patients and Providers Act (MIPPA) of 2008, Pub. Law 110-275.

II. WHILE THE DAP APPEAL IS PENDING Does your client have health insurance?. If not, why isn’t s/he getting Medicaid, Family Health Plus or Child Health Plus?.

There have been many recent changes which expand eligibility and streamline the application process. All/most of your DAP clients should qualify. Significant changes to Medicaid include.

Elimination of the resource test for certain categories of Medicaid applicants/recipients and all applicants to the Family Health Plus program. N.Y. Soc.

As of October 1, 2009, a resource test is no longer required for these categories. Elimination of the fingerprinting requirement. N.Y.

§369-ee, as amended by L. 2009, c. 58, pt.

C, § 62. Elimination of the waiting period for CHPlus. N.Y.

2008, c. 58. Elimination of the face-to-face interview requirement for Medicaid, effective April 1, 2010.

58, pt. C, § 60. Higher income levels for Single Adults and Childless Couples.

L. §366(1)(a)(1),(8) as amended by L. 2008, c.

Higher income levels for Medicaid’s Medically Needy program. N.Y. Soc.

GIS 08 MA/022 More detailed information on recent changes to Medicaid is available at. III. AFTER CLIENT IS AWARDED DAP BENEFITS a.

Medicaid eligibility. Clients receiving even $1.00 of SSI should qualify for Medicaid automatically. The process for qualifying will differ, however, depending on the source of payment.

These clients are eligible for full Medicaid without a spend-down. See N.Y. Soc.

ii. Medicaid coverage is automatic. No separate application/ recertification required.

iii. Most SSI-only recipients are required to participate in Medicaid managed care. See N.Y.

Eligible for full Medicaid since receiving SSI. See N.Y. Soc.

They can still qualify for Medicaid but may have a spend-down. Federal Law allows states to use a “spend-down” to extend Medicaid to “medically needy” persons in the federal mandatory categories (children, caretakers, elderly and disabled people) whose income or resources are above the eligibility level for regular Medicaid. See 42 U.S.C.

§ 1396 (a) (10) (ii) (XIII). ii. Under spend-down, applicants in New York’s Medically Needy program can qualify for Medicaid once their income/resources, minus incurred medical expenses, fall below the specified level.

For an explanation of spend-down, see 96 ADM 15. B. Family Health Plus Until your client qualifies for Medicare, those over-income for Medicaid may qualify for Family Health Plus without needing to satisfy a spend-down.

It covers adults without children with income up to 100% of the FPL and adults with children up to 150% of the FPL.[1] The eligibility tests are the same as for regular Medicaid with two additional requirements. Applicants must be between the ages of 19 and 64 and they generally must be uninsured. See N.Y.

§ 369-ee et. Seq. Once your client begins to receive Medicare, he or she will not be eligible for FHP, because FHP is generally only available to those without insurance.

For more information on FHP see our article on Family Health Plus. IV. LOOMING ISSUES - MEDICARE ELIGIBILITY (WHETHER YOU LIKE IT OR NOT) a.

SSI-only cases Clients receiving only SSI aren’t eligible for Medicare until they turn 65, unless they also have End Stage Renal Disease. B. Concurrent (SSD and SSI) cases 1.

Medicare eligibility kicks in beginning with 25th month of SSD receipt. See 42 U.S.C. § 426(f).

Exception. In 2000, Congress eliminated the 24-month waiting period for people diagnosed with ALS (Lou Gehrig’s Disease.) See 42 U.S.C. § 426 (h) 2.

Enrollment in Medicare is a condition of eligibility for Medicaid coverage. These clients cannot decline Medicare coverage. (05 OMM/ADM 5.

Medicaid Reference Guide p. 344.1) 3. Medicare coverage is not free.

Although most individuals receive Part A without any premium, Part B has monthly premiums and significant cost-sharing components. 4. Medicaid and/or the Medicare Savings Program (MSP) should pick up most of Medicare’s cost sharing.

Most SSI beneficiaries are eligible not only for full Medicaid, but also for the most comprehensive MSP, the Qualified Medicare Beneficiary (QMB) program. I. Parts A &.

B (hospital and outpatient/doctors visits). A. Medicaid will pick up premiums, deductibles, co-pays.

L. § 367-a (3) (a). For those not enrolled in an MSP, SSA normally deducts the Part B premium directly from the monthly check.

However, SSI recipients are supposed to be enrolled automatically in QMB, and Medicaid is responsible for covering the premiums. Part B premiums should never be deducted from these clients’ checks.[1] Medicaid and QMB-only recipients should NEVER be billed directly for Part A or B services. Even non-Medicaid providers are supposed to be able to bill Medicaid directly for services.[2] Clients are only responsible for Medicaid co-pay amount.

See 42 U.S.C. § 1396a (n) ii. Part D (prescription drugs).

a. Clients enrolled in Medicaid and/or MSP are deemed eligible for Low Income Subsidy (LIS aka Extra Help). See 42 C.F.R.

§ 423.773(c). SSA POMS SI § 01715.005A.5. New York State If client doesn’t enroll in Part D plan on his/her own, s/he will be automatically assigned to a benchmark[3] plan.

See 42 C.F.R. § 423.34 (d). LIS will pick up most of cost-sharing.[3] Because your clients are eligible for full LIS, they should have NO deductible and NO premium if they are in a benchmark plan, and will not be subject to the coverage gap (aka “donut hole”).

See 42 C.F.R. §§ 423.780 and 423.782. The full LIS beneficiary will also have co-pays limited to either $1.10 or $3.30 (2010 amounts).

See 42 C.F.R. § 423.104 (d) (5) (A). Other important points to remember.

- Medicaid co-pay rules do not apply to Part D drugs. - Your client’s plan may not cover all his/her drugs. - You can help your clients find the plan that best suits their needs.

To figure out what the best Part D plans are best for your particular client, go to www.medicare.gov. Click on “formulary finder” and plug in your client’s medication list. You can enroll in a Part D plan through www.medicare.gov, or by contacting the plan directly.

€“ Your clients can switch plans at any time during the year. Iii. Part C (“Medicare Advantage”).

a. Medicare Advantage plans provide traditional Medicare coverage (Parts A and B) through private managed care insurers. See 42 U.S.C.

Medicare Advantage participation is voluntary. For those clients enrolled in Medicare Advantage Plans, the QMB cost sharing obligations are the same as they are under traditional Medicare. Medicaid must cover any premiums required by the plan, up to the Part B premium amount.

Medicaid must also cover any co-payments and co-insurance under the plan. As with traditional Medicare, both providers and plans are prohibited from billing the beneficiary directly for these co-payments. C.

SSD only individuals. 1. Same Medicare eligibility criteria (24 month waiting period, except for persons w/ ALS).

I. During the 24 month waiting period, explore eligibility for Medicaid or Family Health Plus. 2.

Once Medicare eligibility begins. ii. Parts A &.

B. SSA will automatically enroll your client. Part B premiums will be deducted from monthly Social Security benefits.

(Part A will be free – no monthly premium) Clients have the right to decline ongoing Part B coverage, BUT this is almost never a good idea, and can cause all sorts of headaches if client ever wants to enroll in Part B in the future. (late enrollment penalty and can’t enroll outside of annual enrollment period, unless person is eligible for Medicare Savings Program – see more below) Clients can decline “retro” Part B coverage with no penalty on the Medicare side – just make sure they don’t actually need the coverage. Risky to decline if they had other coverage during the retro period – their other coverage may require that Medicare be utilized if available.

Part A and Part B also have deductibles and co-pays. Medicaid and/or the MSPs can help cover this cost sharing. iii.

Part D. Client must affirmatively enroll in Part D, unless they receive LIS. See 42 U.S.C.

§ 1395w-101 (b) (2), 42 C.F.R. § 423.38 (a). Enrollment is done through individual private plans.

LIS recipients will be auto-assigned to a Part D benchmark plan if they have not selected a plan on their own. Client can decline Part D coverage with no penalty if s/he has “comparable coverage.” 42 C.F.R. § 423.34 (d) (3) (i).

If no comparable coverage, person faces possible late enrollment penalty &. Limited enrollment periods. 42 C.F.R.

§ 423.46. However, clients receiving LIS do not incur any late enrollment penalty. 42 C.F.R.

§ 423.780 (e). Part D has a substantial cost-sharing component – deductibles, premiums and co-pays which vary from plan to plan. There is also the coverage gap, also known as “donut hole,” which can leave beneficiaries picking up 100% of the cost of their drugs until/unless a catastrophic spending limit is reached.

The LIS program can help with Part D cost-sharing. Use Medicare’s website to figure out what plan is best for your client. (Go to www.medicare.gov , click on “formulary finder” and plug in your client’s medication list.

) You can also enroll in a Part D plan directly through www.medicare.gov. Iii. Help with Medicare cost-sharing a.

Medicaid – After eligibility for Medicare starts, client may still be eligible for Medicaid, with or without a spend-down. There are lots of ways to help clients meet their spend-down – including - Medicare cost sharing amounts (deductibles, premiums, co-pays) - over the counter medications if prescribed by a doctor. - expenses paid by state-funded programs like EPIC and ADAP.

- medical bills of person’s spouse or child. - health insurance premiums. - joining a pooled Supplemental Needs Trust (SNT).

B. Medicare Savings Program (MSP) – If client is not eligible for Medicaid, explore eligibility for Medicare Savings Program (MSP). MSP pays for Part B premiums and gets you into the Part D LIS.

There are no asset limits in the Medicare Savings Program. One of the MSPs (QMB), also covers all cost sharing for Parts A &. B.

If your client is eligible for Medicaid AND MSP, enrolling in MSP may subject him/her to, or increase a spend-down, because Medicaid and the various MSPs have different income eligibility levels. It is the client’s choice as to whether or not to be enrolled into MSP. C.

Part D Low Income Subsidy (LIS) – If your client is not eligible for MSP or Medicaid, s/he may still be eligible for Part D Low Income Subsidy. Applications for LIS are also be treated as applications for MSP, unless the client affirmatively indicates that s/he does not want to apply for MSP. d.

Medicare supplemental insurance (Medigap) -- Medigap is supplemental private insurance coverage that covers all or some of the deductibles and coinsurance for Medicare Parts A and B. Medigap is not available to people enrolled in Part C. E.

Medicare Advantage – Medicare Advantage plans “package” Medicare (Part A and B) benefits, with or without Part D coverage, through a private health insurance plan. The cost-sharing structure (deductible, premium, co-pays) varies from plan to plan. For a list of Medicare Advantage plans in your area, go to www.medicare.gov – click on “find health plans.” f.

NY Prescription Saver Card -- NYP$ is a state-sponsored pharmacy discount card that can lower the cost of prescriptions by as much as 60 percent on generics and 30 percent on brand name drugs. Can be used during the Part D “donut hole” (coverage gap) g. For clients living with HIV.

ADAP [AIDS Drug Assistance Program] ADAP provides free medications for the treatment of HIV/AIDS and opportunistic s. ADAP can be used to help meet a Medicaid spenddown and get into the Part D Low Income subsidy. For more information about ADAP, go to V.

GETTING MEDICAID IN THE DISABLED CATEGORY AFTER AN SSI/SSDI DENIAL What if your client's application for SSI or SSDI is denied based on SSA's finding that they were not "disabled?. " Obviously, you have your appeals work cut out for you, but in the meantime, what can they do about health insurance?. It is still possible to have Medicaid make a separate disability determination that is not controlled by the unfavorable SSA determination in certain situations.

Specifically, an applicant is entitled to a new disability determination where he/she. alleges a different or additional disabling condition than that considered by SSA in making its determination. Or alleges less than 12 months after the most recent unfavorable SSA disability determination that his/her condition has changed or deteriorated, alleges a new period of disability which meets the duration requirement, and SSA has refused to reopen or reconsider the allegations, or the individual is now ineligible for SSA benefits for a non-medical reason.

Or alleges more than 12 months after the most recent unfavorable SSA disability determination that his/her condition has changed or deteriorated since the SSA determination and alleges a new period of disability which meets the duration requirement, and has not applied to SSA regarding these allegations. See GIS 10-MA-014 and 08 OHIP/INF-03.[4] [1] Potential wrinkle – for some clients Medicaid is not automatically pick up cost-sharing. In Monroe County we have had several cases where SSA began deducting Medicare Part B premiums from the checks of clients who were receiving SSI and Medicaid and then qualified for Medicare.

The process should be automatic. Please contact Geoffrey Hale in our Rochester office if you encounter any cases like this. [2]Under terms established to provide benefits for QMBs, a provider agreement necessary for reimbursement “may be executed through the submission of a claim to the Medicaid agency requesting Medicaid payment for Medicare deductibles and coinsurance for QMBs.” CMS State Medicaid Manual, Chapter 3, Eligibility, 3490.14 (b), available at.

http://www.cms.hhs.gov/Manuals/PBM/itemdetail.asp?. ItemID=CMS021927. [3]Benchmark plans are free if you are an LIS recipient.

The amount of the benchmark changes from year to year. In 2013, a Part D plan in New York State is considered benchmark if it provides basic Part D coverage and its monthly premium is $43.22 or less. [4] These citations courtesy of Jim Murphy at Legal Services of Central New York.

This site provides general information only. This is not legal advice. You can only obtain legal advice from a lawyer.

In addition, your use of this site does not create an attorney-client relationship. To contact a lawyer, visit http://lawhelp.org/ny. We make every effort to keep these materials and links up-to-date and in accordance with New York City, New York state and federal law.

However, we do not guarantee the accuracy of this information..

Maximizing health coverage low price zithromax for DAP clients http://baselaunch.biocom.de/cipro-price-comparison/. Before and after winning the case Outline prepared by Geoffrey Hale and Cathy Roberts - updated August 2012 This outline is intended to assist Disability Advocacy Program (DAP) advocates maximize health insurance coverage for clients they are representing on Social Security/SSI disability determinations. We begin with a discussion of coverage options low price zithromax available while your client’s DAP case is pending and then outline the effect winning the DAP case can have on your client’s access to health care coverage. How your client is affected will vary depending on the source and amount of disability income he or she receives after the successful appeal.

I. BACKGROUND low price zithromax. Public health coverage for your clients will primarily be provided by Medicaid and Medicare. The two programs low price zithromax are structured differently and have different eligibility criteria, but in order to provide the most complete coverage possible for your clients, they must work effectively together.

Understanding their interactions is essential to ensuring benefits for your client. Here is a brief overview of the programs we will cover. A. Medicaid.

Medicaid is the public insurance program jointly funded by the federal, state and local governments for people of limited means. For federal Medicaid law, see 42 U.S.C. § 1396 et seq., 42 C.F.R. § 430 et seq.

Regular Medicaid is described in New York’s State Plan and codified at N.Y. Soc. Serv. L.

§§ 122, 131, 363- 369-1. 18 N.Y.C.R.R. § 360, 505. New York also offers several additional programs to provide health care benefits to those whose income might be too high for Regular Medicaid.

i. Family Health Plus (FHPlus) is an extension of New York’s Medicaid program that provides health coverage for adults who are over-income for regular Medicaid. FHPlus is described in New York’s 1115 waiver and codified at N.Y. Soc.

Child Health Plus (CHPlus) is a sliding scale premium program for children who are over-income for regular Medicaid. CHPlus is codified at N.Y. Pub. Health L.

§2510 et seq. b. Medicare. Medicare is the federal health insurance program providing coverage for the elderly, disabled, and people with end-stage renal disease.

Medicare is codified under title XVIII of the Social Security Law, see 42 U.S.C. § 1395 et seq., 42 C.F.R. § 400 et seq. Medicare is divided into four parts.

i. Part A covers hospital, skilled nursing facility, home health, and hospice care, with some deductibles and coinsurance. Most people are eligible for Part A at no cost. See 42 U.S.C.

Part B provides medical insurance for doctor’s visits and other outpatient medical services. Medicare Part B has significant cost-sharing components. There are monthly premiums (the standard premium in 2012 is $99.90. In addition, there is a $135 annual deductible (which will increase to $155 in 2010) as well as 20% co-insurance for most covered out-patient services.

See 42 U.S.C. § 1395k, 42 C.F.R. Pt. 407.

iii. Part C, also called Medicare Advantage, provides traditional Medicare coverage (Parts A and B) through private managed care insurers. See 42 U.S.C. § 1395w, 42 C.F.R.

Pt. 422. Premium amounts for Medicare Advantage plans vary. Some Medicare Advantage plans include prescription drug coverage.

iv. Part D is an optional prescription drug benefit available to anyone with Medicare Parts A and B. See 42 U.S.C. § 1395w, 42 C.F.R.

§ 423.30(a)(1)(i) and (ii). Unlike Parts A and B, Part D benefits are provided directly through private plans offered by insurance companies. In order to receive prescription drug coverage, a Medicare beneficiary must join a Part D Plan or participate in a Medicare Advantage plan that provides prescription drug coverage. C.

Medicare Savings Programs (MSPs). Funded by the State Medicaid program, MSPs help eligible individuals meet some or all of their cost-sharing obligations under Medicare. See N.Y. Soc.

Serv. L. § 367-a(3)(a), (b), and (d). There are three separate MSPs, each with different eligibility requirements and providing different benefits.

i. Qualified Medicare Beneficiary (QMB). The QMB program provides the most comprehensive benefits. Available to those with incomes at or below 100% of the Federal Poverty Level (FPL), the QMB program covers virtually all Medicare cost-sharing obligations.

Part B premiums, Part A premiums, if there are any, and any and all deductibles and co-insurance. ii. Special Low-Income Medicare Beneficiary (SLMB). For those with incomes between 100% and 120% FPL, the SLMB program will cover Part B premiums only.

iii. Qualified Individual (QI-1). For those with incomes between 120% and 135% FPL, but not otherwise Medicaid eligible, the QI-1 program covers Medicare Part B premiums. D.

Medicare Part D Low Income Subsidy (LIS or “Extra Help”). LIS is a federal subsidy administered by CMS that helps Medicare beneficiaries with limited income and/or resources pay for some or most of the costs of Medicare prescription drug coverage. See 42 C.F.R. § 423.773.

Some of the costs covered in full or in part by LIS include the monthly premiums, annual deductible, co-payments, and the coverage gap. Individuals eligible for Medicaid, SSI, or MSP are deemed eligible for full LIS benefitsSee 42 C.F.R. § 423.773(c). LIS applications are treated as (“deemed”) applications for MSP benefits, See the Medicare Improvements for Patients and Providers Act (MIPPA) of 2008, Pub.

Law 110-275. II. WHILE THE DAP APPEAL IS PENDING Does your client have health insurance?. If not, why isn’t s/he getting Medicaid, Family Health Plus or Child Health Plus?.

There have been many recent changes which expand eligibility and streamline the application process. All/most of your DAP clients should qualify. Significant changes to Medicaid include. Elimination of the resource test for certain categories of Medicaid applicants/recipients and all applicants to the Family Health Plus program.

§369-ee (2), as amended by L. 2009, c. 58, pt. C, § 59-d.

As of October 1, 2009, a resource test is no longer required for these categories. Elimination of the fingerprinting requirement. N.Y. Soc.

Serv. L. §369-ee, as amended by L. 2009, c.

58, pt. C, § 62. Elimination of the waiting period for CHPlus. N.Y.

Pub. Health L. §2511, as amended by L. 2008, c.

58. Elimination of the face-to-face interview requirement for Medicaid, effective April 1, 2010. N.Y. Soc.

Serv. L. §366-a (1), as amended by L. 2009, c.

58, pt. C, § 60. Higher income levels for Single Adults and Childless Couples. N.Y.

Soc. Serv. L. §366(1)(a)(1),(8) as amended by L.

Higher income levels for Medicaid’s Medically Needy program. N.Y. Soc. Serv.

L. §366(2)(a)(7) as amended by L. 2008, c. 58.

See also. GIS 08 MA/022 More detailed information on recent changes to Medicaid is available at. III. AFTER CLIENT IS AWARDED DAP BENEFITS a.

Medicaid eligibility. Clients receiving even $1.00 of SSI should qualify for Medicaid automatically. The process for qualifying will differ, however, depending on the source of payment. 1.

Clients Receiving SSI Only. i. These clients are eligible for full Medicaid without a spend-down. See N.Y.

ii. Medicaid coverage is automatic. No separate application/ recertification required. iii.

Most SSI-only recipients are required to participate in Medicaid managed care. See N.Y. Soc. Serv.

L. §364-j. 2. Concurrent (SSI/SSD) cases.

Eligible for full Medicaid since receiving SSI. See N.Y. Soc. Serv.

I. They can still qualify for Medicaid but may have a spend-down. Federal Law allows states to use a “spend-down” to extend Medicaid to “medically needy” persons in the federal mandatory categories (children, caretakers, elderly and disabled people) whose income or resources are above the eligibility level for regular Medicaid. See 42 U.S.C.

§ 1396 (a) (10) (ii) (XIII). ii. Under spend-down, applicants in New York’s Medically Needy program can qualify for Medicaid once their income/resources, minus incurred medical expenses, fall below the specified level. For an explanation of spend-down, see 96 ADM 15.

B. Family Health Plus Until your client qualifies for Medicare, those over-income for Medicaid may qualify for Family Health Plus without needing to satisfy a spend-down. It covers adults without children with income up to 100% of the FPL and adults with children up to 150% of the FPL.[1] The eligibility tests are the same as for regular Medicaid with two additional requirements. Applicants must be between the ages of 19 and 64 and they generally must be uninsured.

§ 369-ee et. Seq. Once your client begins to receive Medicare, he or she will not be eligible for FHP, because FHP is generally only available to those without insurance. For more information on FHP see our article on Family Health Plus.

IV. LOOMING ISSUES - MEDICARE ELIGIBILITY (WHETHER YOU LIKE IT OR NOT) a. SSI-only cases Clients receiving only SSI aren’t eligible for Medicare until they turn 65, unless they also have End Stage Renal Disease. B.

Concurrent (SSD and SSI) cases 1. Medicare eligibility kicks in beginning with 25th month of SSD receipt. See 42 U.S.C. § 426(f).

Exception. In 2000, Congress eliminated the 24-month waiting period for people diagnosed with ALS (Lou Gehrig’s Disease.) See 42 U.S.C. § 426 (h) 2. Enrollment in Medicare is a condition of eligibility for Medicaid coverage.

These clients cannot decline Medicare coverage. (05 OMM/ADM 5. Medicaid Reference Guide p. 344.1) 3.

Medicare coverage is not free. Although most individuals receive Part A without any premium, Part B has monthly premiums and significant cost-sharing components. 4. Medicaid and/or the Medicare Savings Program (MSP) should pick up most of Medicare’s cost sharing.

Most SSI beneficiaries are eligible not only for full Medicaid, but also for the most comprehensive MSP, the Qualified Medicare Beneficiary (QMB) program. I. Parts A &. B (hospital and outpatient/doctors visits).

A. Medicaid will pick up premiums, deductibles, co-pays. N.Y. Soc.

Serv. L. § 367-a (3) (a). For those not enrolled in an MSP, SSA normally deducts the Part B premium directly from the monthly check.

However, SSI recipients are supposed to be enrolled automatically in QMB, and Medicaid is responsible for covering the premiums. Part B premiums should never be deducted from these clients’ checks.[1] Medicaid and QMB-only recipients should NEVER be billed directly for Part A or B services. Even non-Medicaid providers are supposed to be able to bill Medicaid directly for services.[2] Clients are only responsible for Medicaid co-pay amount. See 42 U.S.C.

§ 1396a (n) ii. Part D (prescription drugs). a. Clients enrolled in Medicaid and/or MSP are deemed eligible for Low Income Subsidy (LIS aka Extra Help).

See 42 C.F.R. § 423.773(c). SSA POMS SI § 01715.005A.5. New York State If client doesn’t enroll in Part D plan on his/her own, s/he will be automatically assigned to a benchmark[3] plan.

See 42 C.F.R. § 423.34 (d). LIS will pick up most of cost-sharing.[3] Because your clients are eligible for full LIS, they should have NO deductible and NO premium if they are in a benchmark plan, and will not be subject to the coverage gap (aka “donut hole”). See 42 C.F.R.

§§ 423.780 and 423.782. The full LIS beneficiary will also have co-pays limited to either $1.10 or $3.30 (2010 amounts). See 42 C.F.R. § 423.104 (d) (5) (A).

Other important points to remember. - Medicaid co-pay rules do not apply to Part D drugs. - Your client’s plan may not cover all his/her drugs. - You can help your clients find the plan that best suits their needs.

To figure out what the best Part D plans are best for your particular client, go to www.medicare.gov. Click on “formulary finder” and plug in your client’s medication list. You can enroll in a Part D plan through www.medicare.gov, or by contacting the plan directly. €“ Your clients can switch plans at any time during the year.

Iii. Part C (“Medicare Advantage”). a. Medicare Advantage plans provide traditional Medicare coverage (Parts A and B) through private managed care insurers.

See 42 U.S.C. § 1395w, 42 C.F.R. Pt. 422.

Medicare Advantage participation is voluntary. For those clients enrolled in Medicare Advantage Plans, the QMB cost sharing obligations are the same as they are under traditional Medicare. Medicaid must cover any premiums required by the plan, up to the Part B premium amount. Medicaid must also cover any co-payments and co-insurance under the plan.

As with traditional Medicare, both providers and plans are prohibited from billing the beneficiary directly for these co-payments. C. SSD only individuals. 1.

Same Medicare eligibility criteria (24 month waiting period, except for persons w/ ALS). I. During the 24 month waiting period, explore eligibility for Medicaid or Family Health Plus. 2.

Once Medicare eligibility begins. ii. Parts A &. B.

SSA will automatically enroll your client. Part B premiums will be deducted from monthly Social Security benefits. (Part A will be free – no monthly premium) Clients have the right to decline ongoing Part B coverage, BUT this is almost never a good idea, and can cause all sorts of headaches if client ever wants to enroll in Part B in the future. (late enrollment penalty and can’t enroll outside of annual enrollment period, unless person is eligible for Medicare Savings Program – see more below) Clients can decline “retro” Part B coverage with no penalty on the Medicare side – just make sure they don’t actually need the coverage.

Risky to decline if they had other coverage during the retro period – their other coverage may require that Medicare be utilized if available. Part A and Part B also have deductibles and co-pays. Medicaid and/or the MSPs can help cover this cost sharing. iii.

Part D. Client must affirmatively enroll in Part D, unless they receive LIS. See 42 U.S.C. § 1395w-101 (b) (2), 42 C.F.R.

§ 423.38 (a). Enrollment is done through individual private plans. LIS recipients will be auto-assigned to a Part D benchmark plan if they have not selected a plan on their own. Client can decline Part D coverage with no penalty if s/he has “comparable coverage.” 42 C.F.R.

§ 423.34 (d) (3) (i). If no comparable coverage, person faces possible late enrollment penalty &. Limited enrollment periods. 42 C.F.R.

§ 423.46. However, clients receiving LIS do not incur any late enrollment penalty. 42 C.F.R. § 423.780 (e).

Part D has a substantial cost-sharing component – deductibles, premiums and co-pays which vary from plan to plan. There is also the coverage gap, also known as “donut hole,” which can leave beneficiaries picking up 100% of the cost of their drugs until/unless a catastrophic spending limit is reached. The LIS program can help with Part D cost-sharing. Use Medicare’s website to figure out what plan is best for your client.

(Go to www.medicare.gov , click on “formulary finder” and plug in your client’s medication list. ) You can also enroll in a Part D plan directly through www.medicare.gov. Iii. Help with Medicare cost-sharing a.

Medicaid – After eligibility for Medicare starts, client may still be eligible for Medicaid, with or without a spend-down. There are lots of ways to help clients meet their spend-down – including - Medicare cost sharing amounts (deductibles, premiums, co-pays) - over the counter medications if prescribed by a doctor. - expenses paid by state-funded programs like EPIC and ADAP. - medical bills of person’s spouse or child.

- health insurance premiums. - joining a pooled Supplemental Needs Trust (SNT). B. Medicare Savings Program (MSP) – If client is not eligible for Medicaid, explore eligibility for Medicare Savings Program (MSP).

MSP pays for Part B premiums and gets you into the Part D LIS. There are no asset limits in the Medicare Savings Program. One of the MSPs (QMB), also covers all cost sharing for Parts A &. B.

If your client is eligible for Medicaid AND MSP, enrolling in MSP may subject him/her to, or increase a spend-down, because Medicaid and the various MSPs have different income eligibility levels. It is the client’s choice as to whether or not to be enrolled into MSP. C. Part D Low Income Subsidy (LIS) – If your client is not eligible for MSP or Medicaid, s/he may still be eligible for Part D Low Income Subsidy.

Applications for LIS are also be treated as applications for MSP, unless the client affirmatively indicates that s/he does not want to apply for MSP. d. Medicare supplemental insurance (Medigap) -- Medigap is supplemental private insurance coverage that covers all or some of the deductibles and coinsurance for Medicare Parts A and B. Medigap is not available to people enrolled in Part C.

E. Medicare Advantage – Medicare Advantage plans “package” Medicare (Part A and B) benefits, with or without Part D coverage, through a private health insurance plan. The cost-sharing structure (deductible, premium, co-pays) varies from plan to plan. For a list of Medicare Advantage plans in your area, go to www.medicare.gov – click on “find health plans.” f.

NY Prescription Saver Card -- NYP$ is a state-sponsored pharmacy discount card that can lower the cost of prescriptions by as much as 60 percent on generics and 30 percent on brand name drugs. Can be used during the Part D “donut hole” (coverage gap) g. For clients living with HIV. ADAP [AIDS Drug Assistance Program] ADAP provides free medications for the treatment of HIV/AIDS and opportunistic s.

ADAP can be used to help meet a Medicaid spenddown and get into the Part D Low Income subsidy. For more information about ADAP, go to V. GETTING MEDICAID IN THE DISABLED CATEGORY AFTER AN SSI/SSDI DENIAL What if your client's application for SSI or SSDI is denied based on SSA's finding that they were not "disabled?. " Obviously, you have your appeals work cut out for you, but in the meantime, what can they do about health insurance?.

It is still possible to have Medicaid make a separate disability determination that is not controlled by the unfavorable SSA determination in certain situations. Specifically, an applicant is entitled to a new disability determination where he/she. alleges a different or additional disabling condition than that considered by SSA in making its determination. Or alleges less than 12 months after the most recent unfavorable SSA disability determination that his/her condition has changed or deteriorated, alleges a new period of disability which meets the duration requirement, and SSA has refused to reopen or reconsider the allegations, or the individual is now ineligible for SSA benefits for a non-medical reason.

Or alleges more than 12 months after the most recent unfavorable SSA disability determination that his/her condition has changed or deteriorated since the SSA determination and alleges a new period of disability which meets the duration requirement, and has not applied to SSA regarding these allegations. See GIS 10-MA-014 and 08 OHIP/INF-03.[4] [1] Potential wrinkle – for some clients Medicaid is not automatically pick up cost-sharing. In Monroe County we have had several cases where SSA began deducting Medicare Part B premiums from the checks of clients who were receiving SSI and Medicaid and then qualified for Medicare. The process should be automatic.

Please contact Geoffrey Hale in our Rochester office if you encounter any cases like this. [2]Under terms established to provide benefits for QMBs, a provider agreement necessary for reimbursement “may be executed through the submission of a claim to the Medicaid agency requesting Medicaid payment for Medicare deductibles and coinsurance for QMBs.” CMS State Medicaid Manual, Chapter 3, Eligibility, 3490.14 (b), available at. http://www.cms.hhs.gov/Manuals/PBM/itemdetail.asp?. ItemID=CMS021927.

[3]Benchmark plans are free if you are an LIS recipient. The amount of the benchmark changes from year to year. In 2013, a Part D plan in New York State is considered benchmark if it provides basic Part D coverage and its monthly premium is $43.22 or less. [4] These citations courtesy of Jim Murphy at Legal Services of Central New York.

This site provides general information only. This is not legal advice. You can only obtain legal advice from a lawyer. In addition, your use of this site does not create an attorney-client relationship.

To contact a lawyer, visit http://lawhelp.org/ny. We make every effort to keep these materials and links up-to-date and in accordance with New York City, New York state and federal law. However, we do not guarantee the accuracy of this information..

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Zithromax for pneumonia

Autodesk deployed it’s Octo-Copter in Africa for high resolution reality capture.  This was done in support of Louis Leakey in Kenya in search of our ancestral trails


Additonally, they deployed it on their head quarters in San Rafael.

From the Gizmag Website:

The Mikrokopter Octocopter is an 8-rotor flying platform which has a 2 kg (4.4 lbs) capacity to carry cameras. It can be flown using an internal camera to give the operator a copter-based vantage point on video glasses, or can be programmed to follow a GPS-controlled flight path. An Octocopter can fly autonomously at altitudes up to 1000 meters (3280 feet), or can be manually flown as high as 3500 meters (11,480 feet). In the Autodesk tests video was captured using a GOPro Hero 2 camera, and the still pictures from which the 3D model was later built were taken by a remotely triggered Canon SLR camera.

Autodesk 123D is a suite of programs which allow a user to create, manipulate, and construct 3D objects using a 3D printer. Catch is part of the 123D suite, and offers a standalone software package that helps you create 3D models from a series of 2D digital images of an object or a scene. The spatial resolution available using 123D Catch is about 1 part in 600, or 0.167% of the total size of the object pictured, so you would be able to accurately place individual windows on a 3D model of a Boeing 747.

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Zithromax for pneumonia

Zithromax for pneumonia

Get to the Beach and then Treat Yourself

Cranes Beach & Wingaersheek Beech, Head north on 128.  Enjoy the water, and then take the short drive to Essex and go get fried clams and soft serve, call in your fried clam order if you can.  Try Woodman’s, Farnham’s (they got picnic tables over looking the tidal marsh) or try the Village, and Essex Seafood, which has always been a solid go to.

Horseneck Beach, terrific beach going south on 24, Westport, MA almost always less traffic, then go to the Back Eddy for something to cold to drink and a snack.

You’re in and around the city.

Find a Roof Deck and/or Pool, a variety of posts on the subject from Boston.com, but it seems the Colonade for a pool stop is always mentioned. And outside of the city, Indigo in Newton is pretty nice stop.

Walk the Greenway, play in the fountains, get gelatto, try the Gelateria  in the North End.

Have a cold drink in a well air conditioned bar by the Garden, then walk over the river, across the locks into Charlestown and do the same thing there.  Your choice for locations, there are many.  But go ahead and stop at Emack and Bolio’s on the walk back.

Play in the Fountain at the Christian Science Center, walk into the Pru and Copley to soak in the air conditioning, play “how much are these shoes” at Nordstrom.  Have a friend stand back from the shoe tables, have them guess.  Most likely off by a factor of 10, go get a coolata at Dunkin.

If you are feeling particularly flush and it’s after 5, go get a martini at the Oak Room, used to come with side car sitting in ice.  That will frame the rest of your day.  Air Conditioning set on igloo.

Take your dog for a walk at the Middlesex Fells Reservation, or bring him/her to a pond, throw a stick. Jamaica Pond, Spy Pond, Fresh Pond, etc.  You might not get cool, but look at the dog, so happy.  And now I’ve seen Canoe and Kayak Rentals at Spy Pond.

So there’s a start, generally, a cold drink, cone or a slush, water, you get the idea.

 

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With Microsoft’s announcement of Windows 8, and the unveiling of the Surface Tablet, it finally appears there will be a tablet form factor that will run Revit in the field.  According to the press release there will be two versions, one based on the ARM chip and another based on the Intel i5 chip running Windows 8 Pro.  The iPad, as much it is great for so many tasks, simply does not have the horsepower to run Revit in the field, and delivering the type of user experience one would want with heavyweight programs is a real limitation in the ‘cloud.’  I understand Autodesk is now counting solely on Citrix to provide its remote platform but even if you are driving Revit remotely would you want to rely on whatever internet connection you have?  That’s just not a funnel I would want to count on in the field.

At first glance you might say so what, not a big deal.  However, if I can have a device that toggles between my heavyweight AEC programs, and delivers content the way my my iPad does then I might have an iPad to sell you; because frankly I am sick of devices, I live between the Mac and Windows camp, I’m tired of it.  I used to be an Apple fanatic, even being the only kid in business school with a Mac, the disastrous PowerPC model, but what was not to like about Apple.  Now, how did we get to the point where Microsoft is the little guy, relatively speaking.  Now if they could get their content management into a spot that works the way you want.  Imagine the central Revit model up on the sky drive, you check it out in the field, do your work, update it, booyah.

I think single purpose, highly specific apps are great to digest data,  not for the creation of it so I am real interested in the melding of tablet like functionality with horsepower.  I’m rooting for the little guy, I’m rooting for Microsoft.

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BTW anyone else bother to notice the blending and vertical integration of software/hardware.  Apple, obviously.  Google buys Motorola. Microsoft with multiple attempts, Zune, XBox, etc.  and now Surface. And more germane to AEC Trimble buys Tekla and SketchUp.  Seems to be the biz strategy du jour, watch for more.

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Zithromax for pneumonia

Tweet about PKNail Pro’s Proven Field to BIM Technology, Get Entered Automatically

PointKnown is giving away a free Apple iPad to one lucky Twitterer…er, tweeter, i.e.  one who uses the service twitter to disseminate clever, witty, informative text burst in 140 characters or less.  PointKnown does not claim to be clever, witty or informative, but will claim producing kick ahh…whup ahh…Excellent productivity software tools for documenting existing buildings.

 

 

Zithromax for pneumonia

To participate, simply tweet using the hash tags below:

#pknail #revit #bim and mention ‘PKNail Pro’

Zithromax for pneumonia

PKNail Pro turbo charges Revit and modeling existing buildings #pknail #revit #bim

or “Capture Existing Buildings Directly In Revit with PKNail Pro, 5x-10x faster #pknail #revit #bim

less pertinent but still acceptable “We came, we saw, we conquered with PKNail Pro, #pknail, #bim , #revit

less pertinent verging to the non-sequitur but still acceptable…

beautiful software for happy people PKNail Pro, #pknail, #bim, #revit

or certainly and you are most welcome and encouraged to tweet your own stuff; as we will have a separate drawing of $100 VISA Card for best/most creative tweet as judged by anyone at our next BBQ.

Zithromax for pneumonia


We are on the road with Microcad and have other excellent resellers including,  Seiler Instrument (ask for Harvey) and CADDFX

Zithromax for pneumonia

Zithromax for pneumonia

1. This giveaway is offered by PointKnown LLC and is open to anyone with a Twitter account who is at least 16 years of age. Employees of PointKnown, LLC. and/or its affiliated companies and family members of such employees may enter the contest but are not eligible to win.

2. The giveaway will begin at the time of this post and end 62 days after initial post, a winner will be randomly chosen, much like the number 62, and announced via twitter through @pointknown

3. One giveaway will be available: a 16GB Wi-Fi Apple iPad or $499 Apple Store Credit, winner’s choice.

4. You must prove ownership of the winning entry and provide your email address to collect the prize.

5. To enter the giveaway you must send out a tweet from your own Twitter account that includes the #hash tags above in your message.

6. Entries using automated tweets will be disqualified, however there is no limit on the number of tweets you may enter.

7. PointKnown LLC will choose a winner randomly from all the entries within the specified period. The winner will be announced from our twitter account (@pointknown) once the contest ends.

8. Entrants agree to allow @pointknown to use their twitter handles and entry tweets for marketing purposes.

9. Neither PointKnown LLC. nor its affiliated companies shall have any liability for (i) any technical failures of any kind, including but not limited to malfunctions, interruptions or disconnections in phone lines or network hardware or software; (ii) technical or human error which may occur in the administration of the giveaway; (iii) any malfunction of or damage to the prize; (iv) any corruption, typos or hacking of prize winners email accounts; or (v) any restrictions or delays imposed by any customs authorities or any import or other taxes of any kind imposed by any taxation authority in respect of the prizes.

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Zithromax for pneumonia

Announced today, Autodesk Acquires Vela Systems.  If you are developing products within the Building Life Cycle somewhere between and including design to demolition, you are in play.  Trimble has been going on an acquisition rampage with its acquisition of Tekla and Sketch Up and Autodesk never one to be a wallflower has just acquired Vela.  This is almost 2 years to the date that Vela was unveiled publicly.  No idea of their market size but their own press releases state that they are more than ‘twice as big’ as any competitive Field BIM Systems.  Regardless, market penetration means little at this point now that the Autodesk marketing/sales system is behind it.  How big was Revit in 2006 when they were purchased.  A primer of Vela’s Key Features below.  Congrats Vela folks, job well done.

Vela Field Management Suite Key Features
The Vela Field Management Suite of Web, Mobile and Reports enables everyone throughout the enterprise to access documents, field activities and reports in the office and in the field. Since its release a year ago, and to further broaden the usability throughout the enterprise, Vela Systems has expanded upon the following features:

  • Field BIM® for commissioning and handover that ties BIM to the field for data and document exchange
  • Company-level checklist and issue template capabilities to implement and enforce quality and safety programs
  • Increased accessibility via the Internet on multiple devices like iPads and Smart Phones
  • Better web-based reporting that turns field data into powerful information for managing quality, safety and risk at the project and company level
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As reported by Industry Week, ‘The world’s most sophisticated malware had a ‘high interest in AutoCAD drawings,’ Kaspersky Lab said.  The Flame Virus, which mainly affected computers in the Middle East used a loophole in Microsoft software tricking computers into thinking they are downloading a legitimate Windows update.  This fact, being reported by Reuters, The Times, CNET, and others. CNN reported that Flame can turn on your microphone, webcam, log e-mails, etc.  I have not read if it can do anything malicious itself as the Stuxnet Virus did to Iran Uranium enrichment facilities by having centrifuges essentially tear themselves apart.  However, going after CAD, essentially engineering and building documents can let whoever is collecting this information know what you are designing and building, and possibly have the blueprints of the building you are designing and building in.  And you thought google knowing that you smoke cigars and eat ice cream on your back porch at 5:23 PM was intrusive.

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File under cool.   The City of New York has unveiled an initiative for the electronic submission of BIM safety plans; you can learn more here; and a  Turner Press Release yesterday stated they used both 2D and 3D BIM submissions to get approval for their construction project at the Energy Building at NYU Langone Medical Center.

“The digital submission of 3D, BIM-based site safety plans reduced the approval times from weeks to days,” said Di Fillipo, Turner Senior Vice President.

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The more demos I go on, the more I get asked about our field kit, so I wanted to post what’s in my bag and what we use on a day to day basis when surveying/modeling in the field with PKNail Pro.  Those of you not interested in the day-in day-out particulars of surveying buildings may want to hit your back button now… Anyway an individual equally equipped will be ready for knocking out BIM Building Surveys, and this kit, all in, costs a fraction of most other technology solutions, plus the added benefit of surveying/modeling directly in the platform you or your clients are most likely working in.  However, always choose the tool/service that fits your needs.  In fact, we’ll be posting shortly where we combined workflows of PKNail Pro and pointclouds.  But here you go, what’s in my bag or my complete kit.

So it might seem like a lot but all fits in the bag except for the tripods.  The laptop tripod is excellent when mobility/portability with your gear is at a premium but I will use a laptop cart with wheels if the space allows;  it is easier with wheels and has more surface area to put stuff.

The real minimum you need to have with you is a laptop/tablet PC running the appropriate software, a Disto D8 or 330i, a measuring tape, and something to use for a target when needed, like an outside corner.  Stickynotes (larger size) are excellent for shorter distances, a reflective Leica Target attached with Painter’s Tape is better for longer ones.  Rechargeable batteries for both the laptop and Disto.  I prefer an external battery pack for the laptop as it can be used on any laptop and it is self contained unlike an extra battery for a specific laptop.

I  like Eneloop rechargeables for devices, my preference, they come preloaded with a charge, and seem to carry it longer when not being used.  You need a measuring tape on occasion for distances to short or sometimes nice to hook something with a tape when finding a distance manually.  I like thick banded measuring tapes because they will extend longer without ‘breaking’ but find they are just as prone to wear down as any other so sometimes not worth the expense.  LED flashlight because they are bright and do not use as much juice as others, and are always nice to have.  I also have an LED light that you can wear on your head, which is my preferred.  Diameter tape is a luxury but one side is graduated the other will measure the diameter of any round column which is helpful.

The tripod attachment from Leica allows it to pivot properly on the its axis so the measurements stay as accurate as possible.  This is great to have for exterior work  when you might not have access to the interior of the building.  Building chalk or a marking crayon can be helpful but usually would want to mark with painters tape or sticky pad because they are easily removed, however, the former comes in handy sometimes, especially in basements.

And bring food and drink, nothing clouds your mind like being hungry, so eat.

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Zithromax for pneumonia

Interioreview, utilized PKNail Pro, an add in to Revit, combined with Leica Disto D8 laser range finders as the main surveying tool and software for capturing and modeling the 28 Story DuBois Library at UMass Amherst.  The structure designed by Durell Stone in 1966 is tallest library in the United States.  While intially considering combining LIDAR and creating a pointcloud for the exterior and utilizing PKNail Pro for the interior it turned out the exterior was the easiest part of the job and it was interior that was the most difficult.  Every 3rd floor contained  90+ rooms  with study carrels combined with classrooms where very few technologies would work well.  Nico Martinez, a Project Manager with Interioreview, commented,”Without PKNail the survey work could have taken  5 times, 10 times what it was.”

The project was completed to support the design and retrofitting a fire protection system.

Interioreview, an architecural surveying firm founded in 2003 specialzies in documenting the built environment in both 2D CAD and 3D Revit formats.

PointKnown, a software firm, founded in 2008 develops productivity tools for the built environment / AEC (Architectural, Engineering, and Construction) Industry

PKNail Pro, allows a user to measure and model objects in real time directly in Revit.

Autodesk® Revit® software is specifically built for Building Information Modeling (BIM), helping building professionals design, build, and maintain higher-quality, more energy-efficient buildings.

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