Daily Archives: March 7, 2017

World’s largest autism genome database shines new light on many ‘autisms’ – Medical Xpress

Posted: March 7, 2017 at 9:52 pm

March 7, 2017 Quinn, an autistic boy, and the line of toys he made before falling asleep. Repeatedly stacking or lining up objects is a behavior commonly associated with autism. Credit: Wikipedia.

The newest study from the Autism Speaks MSSNG project - the world's largest autism genome sequencing program - identified an additional 18 gene variations that appear to increase the risk of autism.

The new report appears this week in the journal Nature Neuroscience. It involved the analysis of 5,205 whole genomes from families affected by autism - making it the largest whole genome study of autism to date.

The omitted letters in MSSNG (pronounced 'missing') represent the missing information about autism that the research program seeks to deliver.

"It's noteworthy that we're still finding new autism genes, let alone 18 of them, after a decade of intense focus," says study co-author Mathew Pletcher, Ph.D., Autism Speaks' vice president for genomic discovery. "With each new gene discovery, we're able to explain more cases of autism, each with its own set of behavioral effects and many with associated medical concerns."

To date, research using the MSSNG genomic database has identified 61 genetic variations that affect autism risk. The research has associated several of these with additional medical conditions that often accompany autism. The goal, Dr. Pletcher says, "is to advance personalized treatments for autism by deepening our understanding of the condition's many subtypes."

The findings also illustrate how whole genome sequencing can guide medical care today. For example, at least two of the autism-associated gene changes described in the paper were associated with increased risk for seizures. Another has been linked to increased risk for cardiac defects, and yet another with adult diabetes. The findings illustrate how whole genome sequencing for autism can provide additional medical guidance to individuals, families and their physicians, the investigators say.

The researchers also determined that many of the 18 newly identified autism genes affect the operation of a small subset of biological pathways in the brain. All of these pathways affect how brain cells develop and communicate with each other. "In all, 80 percent of the 61 gene variations discovered through MSSNG affect biochemical pathways that have clear potential as targets for future medicines," Dr. Pletcher says.

Increasingly, autism researchers are predicting that personalized, more effective treatments will come from understanding these common brain pathways - and how different gene variations alter them.

"The unprecedented MSSNG database is enabling research into the many 'autisms' that make up the autism spectrum," says the study's senior investigator, Stephen Scherer, Ph.D.

For instance, some of the genetic alterations found in the study occurred in families with one person severely affected by autism and others on the milder end of the spectrum, Dr. Scherer notes. "This reinforces the significant neurodiversity involved in this complex condition," he explains. "In addition, the depth of the MSSNG database allowed us to identify resilient individuals who carry autism-associated gene variations without developing autism. We believe that this, too, is an important part of the neurodiversity story."

Dr. Scherer is the research director for the MSSNG project and directs The Centre for Applied Genomics at the Hospital for Sick Children (SickKids), in Toronto. MSSNG is a collaboration between the hospital, Autism Speaks and Verily (formerly Google Life Sciences), which hosts the MSSNG database on its cloud platform.

Traditional genetic analysis looks for mutations, or "spelling changes," in the 1 percent of our DNA that spells out our genes. By contrast, the MSSNG database allows researchers to analyze the entire 3 billion DNA base pairs that make up each person's genome.

In their new study, the investigators went even further - looking beyond DNA "spelling" variations to find other types of genetic changes associated with autism. These included copy number variations (repeated or deleted stretches of DNA) and chromosomal abnormalities. Chromosomes are the threadlike cell structures that package and organize our genes.

The researchers found copy number variations and chromosomal abnormalities to be particularly common in the genomes of people affected by autism.

In addition, many of the copy number variations turned up in areas of the genome once considered "junk DNA." Though this genetic "dark matter" exists outside of our genes, scientists now appreciate that it helps control when and where our genes switch on and off. The precise coordination of genetic activity appears to be particularly crucial to brain development and function.

Through its research platform on the Google Cloud, Autism Speaks is making all of MSSNG's fully sequenced genomes directly available to researchers free of charge, along with analytic tools. In the coming weeks, the MSSNG team will be uploading an additional 2,000 fully sequenced autism genomes, bringing the total over 7,000.

Currently, more than 90 investigators at 40 academic and medical institutions are using the MSSNG database to advance autism research around the world.

Explore further: Largest-ever autism genome study finds most siblings have different autism-risk genes

More information: Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder, Nature Neuroscience (2017). DOI: 10.1038/nn.4524

Journal reference: Nature Neuroscience

Provided by: Autism Speaks

The largest-ever autism genome study, funded by Autism Speaks, reveals that the disorder's genetic underpinnings are even more complex than previously thought: Most siblings who have autism spectrum disorder (ASD) have different ...

A new study from Autism Speaks' MSSNG program expands understanding of autism's complex causes and may hold clues for the future development of targeted treatments. The report, appearing in npj Genomic Medicine is the largest-ever ...

Autism Speaks, the world's leading autism science and advocacy organization, today launched the web-based portal for its MSSNG database, making the resource available to researchers worldwide. The MSSNG portal enables qualified ...

A new study from investigators with the Autism Genome Project, the world's largest research project on identifying genes associated with risk for autism, has found that the comprehensive use of copy number variant (CNV) genetic ...

Autism Speaks, the world's largest autism science and advocacy organization, and BGI, the largest genomic organization in the world and a global leader in whole genome sequencing, jointly announce their partnership to create ...

Princeton University and Simons Foundation researchers have developed a machine-learning approach that for the first time analyzes the entire human genome to predict which genes may cause autism spectrum disorder, raising ...

Since the first case was documented in the United States in 1938, the causes of autism have remained elusive. Hundreds of genes, as well as environmental exposures, have been implicated in these brain disorders. Sex also ...

The newest study from the Autism Speaks MSSNG project - the world's largest autism genome sequencing program - identified an additional 18 gene variations that appear to increase the risk of autism.

Concrete links between the symptoms of autism and synaesthesia have been discovered and clarified for the first time, according to new research by psychologists at the University of Sussex.

A national research network led by UNC School of Medicine's Joseph Piven, MD, found that many toddlers diagnosed with autism at two years of age had a substantially greater amount of extra-axial cerebrospinal fluid (CSF) ...

Results of a small study of adults with autism at Johns Hopkins has added to evidence that their brains can learn to compensate for some language comprehension challenges that are a hallmark of the disorder in children.

In the February 2017 issue of Pediatrics, investigators representing the South Carolina Act Early Team report a five-fold increase in the number of children with autism spectrum disorder (ASD) eligible for early intensive ...

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Genome editing: Pressing the ‘delete’ button on DNA – Science Daily

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Genome editing: Pressing the 'delete' button on DNA
Science Daily
CRISPR-Cas9 is a revolutionary technique for editing genomes and until recently, most studies employing it were aimed at silencing protein-coding genes, the best-studied part of our genome. However our genome consists of 99% of DNA that does not ...

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Longevity claims – Wikipedia

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Longevity claims are unsubstantiated cases of asserted human longevity. Those asserting lifespans of 110 years or more are referred to as supercentenarians. Many have either no official verification or are backed only by partial evidence. Cases where longevity has been fully verified, according to modern standards of longevity research, are reflected in an established list of supercentenarians based on the work of organizations such as the Gerontology Research Group (GRG) or the Guinness World Records. This list includes claims between 115 years and 130 years.

Prior to the 19th century, there was insufficient evidence either to demonstrate or to refute centenarian longevity.[1] Even today, no fixed theoretical limit to human longevity is apparent.[2] Studies[1] in the biodemography of human longevity indicate a late-life mortality deceleration law: that death rates level off at advanced ages to a late-life mortality plateau. This implies that there is no fixed upper limit to human longevity, or fixed maximum human lifespan.[3] Researchers in Denmark have found a way to determine when a person was born using radiocarbon dating done on the lens of the eye.[4]

In 1955, Guinness World Records began maintaining a list of the verified oldest people.[5] It developed into a list of all supercentenarians whose lifespan had been verified by at least three documents, in a standardized process, according to the norms of modern longevity research. Many unverified cases ("claims" or "traditions") have been controverted by reliable sources. Taking reliable demographic data into account, these unverified cases vary widely in their plausibility.

Despite demographic evidence of the known extremes of modern longevity, stories in otherwise reliable sources still surface regularly, stating that these extremes have been exceeded. Responsible, modern, scientific validation of human longevity requires investigation of records following an individual from birth to the present (or to death); purported longevity far outside the demonstrated records regularly fail such scrutiny.

Actuary Walter G. Bowerman stated that ill-founded longevity assertions originate mainly in remote, underdeveloped regions, among non-literate peoples, with only family testimony available as evidence.[7] This means that people living in areas of the world with historically more comprehensive resources for record-keeping have tended to hold more claims to longevity, regardless of whether or not individuals in other parts of the world have lived longer.

In the transitional period of record-keeping, records tend to exist for the wealthy and upper-middle classes, but are often spotty and nonexistent for the middle classes and the poor. In the United States, birth registration did not begin in Mississippi until 1912 and was not universal until 1933. Hence, in many longevity cases, no actual birth record exists. This type of case is classified by gerontologists as "partially validated".[citation needed]

Since some cases were recorded in a census or in other reliable sources, obtainable evidence may complete full verification.

In another type of case, the only records that exist are late-life documents. Because age inflation often occurs in adulthood (to avoid military service or to apply for a pension early), or because the government may have begun record-keeping during an individual's lifetime, cases unverified by proximate records exist. These unverified cases are less likely to be true (because the records are written later), but are still possible. Longevity narratives were not subjected to rigorous scrutiny until the work of William Thoms in 1873. Thoms proposed the 100th-birthday test: is there evidence to support an individual's claimed age at what would be their centenary birthday?[9][10] This test does not prove a person's age, but does winnow out typical pension-claim longevity exaggerations and spontaneous claims that a certain relative is over 150.

These are standardized lists of people whose lifespans remain unverified by proximate records, including both modern (Guinness-era) and historical cases. Claims missing either (or both) a date of birth/date of death are listed separately. All cases in which an individual's supercentenarian lifespan is not (yet) backed by records sufficient to the standards of modern longevity research are listed as unverified. They may be factually true, even though records do not exist (or have not yet been found), so such lists include these grey-area cases.

These living supercentenarian cases, in descending order of claimed age, with full birth and review dates, have been updated within the past two years, but have not had their claimed age validated by an independent body such as the Gerontology Research Group or Guinness World Records. Only claims over 115 years but under 130 years are included in the list.

This table contains supercentenarian claims with either a known death date or no confirmation for more than 2 years that they were still alive. Only claims of ages 115129 are included. They are listed in order of age as of the date of death or date last reported alive.

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Future Human lifespan 140 years, 500 years, 1000 years or indefinite with aging damage repair and aging reversal – Next Big Future

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Speaking at the Aspen Abu Dhabi Ideas Forum, Dr Brad Perkins, chief medical officer, Human Longevity, said: Right now the most daunting and expensive human health problem that the world is facing is age related chronic disease. Our hypothesis at Human Longevity is that genomics and the technologies that support its application in medicine and drug discovery are going to be the next accelerant in extending a high performance human lifespan

Human Longevity Inc has been funded with over $220 million and was founded by Craig Venter, Peter Diamandis and Robert Hariri.

Dr. Brad Perkins and other anti-aging researchers at commercial companies made the more conservative for anti-aging researchers that within about 40 years human longevity (maximum lifespan) will reach 140 years. Current life expectancy is about 80 years but with some countries and states at about 90 years for women. The confirmed longest lived person reached 122 years of age.

Aubrey de Grey, a biomedical gerontologist based in Mountain View, California, US, and chief science officer of SENS Research Foundation, a California-based biomedical research charity that performs and funds laboratory research dedicated to combating the aging process, argued that the first person to live to 1,000 years is already probably alive today.

He further commented that fixing ageing is difficult, but not impossible and the only way in which people are going to stay alive a long time is by staying healthy a long time. His focus is on constantly repairing the known sources of aging damage before it becomes complicated disease.

Human Longevity, Inc. (HLI) is the genomics-based, technology-driven company creating the worlds largest and most comprehensive database of whole genome, phenotype and clinical data. HLI is developing and applying large scale computing and machine learning to make novel discoveries to revolutionize the practice of medicine. HLIs business also includes the HLI Health Nucleus, a genomic powered clinical research program which uses whole genome sequence analysis, advanced clinical imaging and innovative machine learning, along with curated personal health information, to deliver the most complete picture of individual health.

Peter Diamandis (Human Longevity co-founder) has argued at other conferences that technology should be able to enable humans to live as at least long as the longest lived large vertebrate. The Greenland shark has been to live 392 120 years old, resulting in a minimum age of 272 and a maximum of 512. That makes the Greenland shark the longest-lived vertebrate.

SOURCES - Trade Arabia, Human Longevity Inc, Peter Diamandis, George Church

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Research gaps persist in psoriasis, psoriatic arthritis | Dermatology … – ModernMedicine

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Orlando The advent of increasingly effective and still costly biologic drugs for psoriasis and psoriatic arthritis (PsA) has highlighted the fact that dermatologists do not know which patients would benefit most from preventative measures.

A key unanswered question in psoriasis is whether physicians can predict and therefore prevent progression to PsA, said Mark Lebwohl, M.D. He is Sol and Clara Kest Professor and Chairman, Department of Dermatology, Icahn School of Medicine at Mount Sinai.

Before biologics, "The drugs that we had helped the pain of arthritis but were not dramatically effective at preventing joint destruction. Methotrexate is a classic example patients still benefit from it today, but the joints continue to deteriorate as evidenced by x-rays."

Tumor necrosis factor (TNF) alpha inhibitors were the first drug class allowed to claim that they prevent radiographic progression of PsA. "Etanercept was the first, followed by infliximab and adalimumab. Then came golimumab and certolizumab. These 5 drugs are dramatically effective for psoriatic arthritis they don't just get rid of the pain, but they also prevent x-ray progression."

More recently, the interleukin (IL) 17 blockers secukinumab and ixekizumab have shown similar abilities. "We have quite a few tools now to prevent joint damage. If we knew in advance which patients with psoriasis were going to develop psoriatic arthritis, it would help us help our patients. We could put them on those drugs early to prevent joint damage."

Among patients with psoriasis and PsA, he said, 72% present with psoriasis first. MRIs can show bone marrow edema (a sign of impending joint damage), "But we need better tests to predict which patients will get psoriatic arthritis." To that end, said Dr. Lebwohl, several companies are investigating genetic markers, while physicians continue to explore use of imaging modalities. "A genetic or serologic marker would be most helpful."

Similarly, researchers are attempting to predict which patients will develop other comorbidities such as cardiovascular disease. "When the biologics came out, patients were put into registries. And we've been finding, particularly with the TNF blockers, that there's a dramatic reduction in heart attacks in people who take these drugs."

A third knowledge gap, Dr. Lebwohl said, is which patients will respond to which treatments. "The new treatments that are coming out are dramatically effective in almost everybody. The problem is, they all cost a fortune." Knowing which patients would likely respond best and which ones would do just as well with cheaper treatments will help dermatologists and their patients immensely, he said.

Disclosures: Dr. Lebwohl has been a clinical investigator for most manufacturers of drugs for psoriasis and psoriatic arthritis. All payments from these companies go not to him but to Mount Sinai.

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DalCor’s Phase 3 Cardiovascular Trial, dal-GenE, Exceeds Targeted Enrollment Schedule – Yahoo Finance

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-- Dalcetrapib Studied in Genetically Distinct Patients with Acute Coronary Syndrome --

LONDON and MONTREAL, March 7, 2017 /PRNewswire/ --DalCor Pharmaceuticals today announced it is ahead of the enrollment schedule with the randomization of over 1,000 patients of the expected 5,000 patients planned for the Phase 3 "dal-GenE" clinical trial, a cardiovascular outcomes study of dalcetrapib in patients with acute coronary syndrome (ACS) and the AA genotype in the ADCY9 gene. Patients have been recruited at 642 hospitals in 30 countries, including the U.S., and on six continents.

The worldwide clinical trial is led by the Montreal Health Innovations Coordinating Center (MHICC), the Lead Academic Research Organization (ARO) and Medpace a leading Clinical Research Organization (CRO).

Approximately 1 in 5 of the general population harbor the AA genotype.

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Jean-Claude Tardif, C.M., M.D., director of the Research Center at the Montreal Heart Institute and professor of medicine at the Universit de Montral, and Principal Investigator for dal-GenE said, "We are pleased and gratified that recruitment goals are ahead of schedule. This is a testament to the need for precision medicine in this critically important sector of medicine; the DalCor approach is the first for cardiovascular medicine. Furthermore, it clearly shows the interest in the study and the necessity for a new therapeutic alternative for patients."

Marc Pfeffer, Dzau Professor of Medicine, Harvard Medical School, Senior Physician, Brigham and Women's Hospital, Consultant to the dal-GenE executive committeeand chair of the prior dal-Outcomes Safety Committee, said, "This impressive recruitment despite requiring a specific genotypereflects well on bothDalCor's experiencedinternational leadership team as well as the motivation of sites and their patients to be part of this major trial addressing a genetically targeted "precision medicine" approach. When completed, dal-GenE will be the first major test of pharmacogenetically profiling patients to improve prognosis following a recent myocardial infarction."

Donald Black, M.D., chief medical officer of DalCor, said, "This significant milestone is the result of the efforts of multiple parties collaborating around the world. Our clinical team, in partnership with a strong network of investigators and other groups, such as ANMCO in Italy, GLCC in New Zealand and ECLA in Argentina and Chile, have been able to work together and significantly improve the study's recruitment rate. It is the hard work of the dedicated team that has enabled the surprisingly quick physician response that has enabled DalCor to reach this important milestone in the short time since initiation.

We believe this compound has a unique profile and possesses a unique combination of safety and efficacy attributes for targeted patients which has the potential to greatly improve outcomes for patients worldwide.

There is much ahead, but DalCor is committed to completing this high-quality trial to obtain a reliable answer to this important question. For now, we look forward to continuing our clinical work in the dal-GenE trial, where we expect to demonstrate a significant reduction in heart attacks, strokes and cardiovascular deaths with the addition of dalcetrapib to the standard of care including statins in patients with ACS and the appropriate genetic profile."

About DalcetrapibDalcetrapib is the first precision medicine in the cardiovascular space to have reached full-scale development with this Phase III clinical study. Over 17,000 patients have participated in dalcetrapib clinical trials to date.

In 2012, investigators at the Montreal Heart Institute led by Professors Jean-Claude Tardif and Marie-Pierre Dub found a significant association between the effects of dalcetrapib in altering CV events and the polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene. Patients with the AA genotype had a 39% reduction in CV events when treated with dalcetrapib compared to placebo, while GG patients had a 27% increase and AG patients had a neutral effect. This analysis was conducted in 5749 patients. A prospective analysis of the dal-Plaque 2 study data has also demonstrated reduced atherosclerosis in the AA population when treated with dalcetrapib, but an increase in atherosclerosis in the GG population.

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About the dal-GenE StudyThe double-blind, randomized, placebo-controlled, multicenter Phase 3 clinical trial will enroll 5,000 patients recently hospitalized with ACS and who express the AA genotype at variant rs1967309 in the ADCY9 gene, determined by an investigational companion diagnostic test developed by Roche Molecular Systems (RMS).

The primary endpoint of the study is the time to first occurrence of any component of the composite of cardiovascular death, myocardial infarction (heart attack) and stroke. The trial will be conducted at 880 sites in 33 countries.

About DalCor PharmaceuticalsDalCor is developing precision treatments by genetically targeting patients that will derive clinical benefits. By integrating clinical and genetic insights, DalCor intends to deliver superior clinical cardiovascular outcomes. The company's first development program, dalcetrapib, is intended to reduce cardiovascular events in a specific genetic subset of patients.

DalCor secured a worldwide exclusive license for dalcetrapib together with rights to the genetic marker for use with dalcetrapib and is sponsoring the dal-GenE study, which is planned to include 5,000 patients to prospectively confirm the results of the pharmacogenomic analysis in the dal-Outcomes study in a patient population with the AA genotype at the rs1967309 location in the ADCY9 gene.

DalCor Pharmaceuticals has offices in Montreal, San Mateo, Calif., Zug, Switzerland and Stockport, U.K. For more information, visit http://www.dalcorpharma.com.

About the Montreal Heart InstituteFounded in 1954 by Dr. Paul David, the Montreal Heart Institute constantly aims for the highest standards of excellence in the cardiovascular field through its leadership in clinical and basic research, ultra-specialized care, professional training and prevention. It is part of the broad network of health excellence made up of Universit de Montral and its affiliated institutions. The Montreal Heart Institute ranks as the No. 1 research hospital in Canada for research intensity and research funds per researcher, according to Research Infosource. For more information, please visit http://www.icm-mhi.org.

DalCor Contacts:

CorporateDalCor PharmaceuticalsDonald M. Black, MD (609) 613-6637 dblack@dalcorpharma.com

MediaRusso PartnersAlexander Fudukidis (646) 942-5632 alex.fudukidis@russopartnersllc.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/dalcors-phase-3-cardiovascular-trial-dal-gene-exceeds-targeted-enrollment-schedule-300418898.html

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DalCor's Phase 3 Cardiovascular Trial, dal-GenE, Exceeds Targeted Enrollment Schedule - Yahoo Finance

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New genetic research provides hope for families with rare diseases – the Irish News

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New genetic research provides hope for families with rare diseases
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The centre, spearheaded by consultant in genetic medicine Dr Shane McKee, have been involved in the design and operation of the UK-wide Deciphering Developmental Disorders (DDD) Study since 2011. The DDD Study involves scientists sequencing the ...

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Genetic driver behind rare skeletal dysplasia condition found – Baylor College of Medicine News (press release)

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Researchers in the Department of Molecular and Human Genetics at Baylor College of Medicine have identified a previously unimplicated gene behind a particular form of chondrodysplasia, a skeletal dysplasia that affects cartilage formation and causes disproportionate short stature and premature osteoarthritis. The study appears in the Journal of Clinical Investigation.

Stemming from research being performed at Baylor and its genetics department as part of a systematic search for genetic causes of skeletal dysplasias, the project set out to identify the genetic driver behind Shohat type spondyloepimetaphyseal dysplasia (SEMD). It was led by Dr. Brendan Lee, professor and chair of molecular and human genetics at Baylor, and a team of researchers including project leader Adetutu Egunsola, a genetics graduate student.

SEMD is a rare type of skeletal dysplasia that impacts the development of cartilage and results in a form of dwarfism, characterized by a particular pattern of joint abnormalities, scoliosis and defects of the long bones.

Through combined whole exome sequencing and studies in zebrafish and mice, Lee and his team were able to identify a completely new gene associated with this skeletal dysplasia, DDRGK1, and discovered how it functions in cartilage. In zebrafish, for example, a DDRGK1 deficiency disrupts craniofacial cartilage development and causes a decrease in levels of the protein SOX9.

Not only did we discover the requirement of DDRGK1 in maintaining cartilage, but we also found that it to be a regulator of SOX9, which is the master transcription factor that controls cartilage formation the human skeleton, said Lee, who also holds the Robert and Janice McNair Endowed Chair in molecular and human genetics. If you do not have the SOX9 protein, you do not have cartilage it drives the production of cartilage in growth plates and joint cartilage all over the body.

The relationship between DDRGK1 and SOX9 reveals a novel mechanism that regulates chondrogenesis, or cartilage maintenance and formation, by controlling SOX9 ubiquitination, a process that controls the degradation of proteins like SOX9. Loss of the function of DDRGK1 causes this cartilage dysplasia in part via accelerated destruction of SOX9.

Studying this skeletal dysplasia resulted in the biological insight about this gene that had never been implicated in any disease condition related to the skeleton, Lee said. The future is to find out whether DDRGK1s function more globally controls ubiquitination in general and to determine how this process could be targeted for treating patients with dwarfism.

Other contributors to this work include Richard Gibbs, Adetutu T. Egunsola, Yangjin Bae, Ming-Ming Jiang, David S. Liu, Yuqing Chen-Evenson, Terry Bertin, Shan Chen and James T. Lu with Baylor, Nurit Magal with Rabin Medical Center, Annick Raas-Rothschild with Sheba-Tel Hashomer Medical Center, Eric C. Swindell with the University of Texas Graduate School of Biomedical Sciences, Lisette Nevarez and Daniel H. Cohn with the University of California, Philippe M. Campeau with the University of Montreal and Mordechai Shohat with the Sackler School of Medicine at Tel Aviv University.

This research was supported by the BCM Intellectual and Developmental Disabilities Research Center and a Program Project grant from the Eunice and Kennedy Shiver National Institute of Child Health and Human Development, the BCM Advanced Technology Cores with funding from the NIH, the Rolanette and Berdon Lawrence Bone Disease Program of Texas, the BCM Center for Skeletal Medicine and Biology and Tel Aviv University.

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Gene activity in the nose may signal lung cancer – KFGO

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Tuesday, March 07, 2017 5:23 p.m. CST

By Will Boggs MD

(Reuters Health) - Genetic changes in the cells lining the inside of the nose might someday help doctors diagnose lung cancer, a recent study suggests.

The idea that you don't have to sample the disease tissue but can diagnose presence of disease using relatively accessible cells that are far from the tumor . . . is a paradigm that can impact many cancers, Dr. Avrum Spira from Boston University School of Medicine, a member of the study team, told Reuters Health by email.

The layer of cells that covers the surfaces of the body and lines the cavities is known as the epithelium. Researchers found that distinctive changes in gene activity in the nasal epithelium of lung cancer patients closely parallel the changes seen in lung epithelium and can distinguish between benign lung disease and cancer.

"I think the most interesting finding was the genomic changes in the nasal epithelium of lung cancer patients mirror so closely those found in the lower airway, Spira said.

The researchers thought the nose would be a reasonable surrogate for the field of injury in the bronchial airway, he added, but the surprisingly strong concordance between the nose and lower airway gave them the encouragement to develop a nasal biomarker for lung cancer detection.

Pulmonary nodules represent a growing diagnostic dilemma in the U.S. as we have started to screen for lung cancer, Spira said. A nasal swab that is highly sensitive for lung cancer in this setting would enable physicians to avoid unnecessary invasive biopsies in nodule patients who are unlikely to have lung cancer.

Past research has found that gene expression profiles from normal bronchial epithelial cells can distinguish smokers and former smokers with lung cancer from individuals with benign lung disease, and that nasal and bronchial epithelium respond similarly to tobacco smoke.

Spiras team sought to determine whether cancer-associated gene expression in the nasal epithelium might be useful for detecting lung cancer in current and former smokers.

They identified 535 genes that had different activity patterns in the nasal epithelium of patients with lung cancer versus those with benign disease.

Cancer-associated gene changes correlated significantly between nasal epithelium and bronchial epithelium samples, and the genes that were more active in nasal epithelium of patients with lung cancer were among the genes whose activity was most increased in bronchial epithelium of patients with cancer.

When researchers compared models doctors might use to determine the likelihood of lung cancer, nasal gene activity was more accurate than clinical risk factors alone for diagnosing lung cancer, according to the Journal of the National Cancer Institute report.

The combination of clinical factors and gene activity score accurately predicted cancer 91 percent of the time, compared to 79 percent for the model based on risk factors. The combined model also had 85 percent accuracy differentiating lung cancer from benign disease, compared to 73 percent.

One of the big-picture messages for physicians is that molecular tests like this one are emerging as part of precision medicine approaches for early cancer detection, Spira said.

SOURCE: http://bit.ly/2mdEWcl Journal of the National Cancer Institute, online February 27, 2017.

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Politically Incorrect | Criminal Case Wiki | Fandom powered …

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Politically Incorrect is a case featured in Criminal Case as the one hundred sixty-eighth case of the game. It is the fifty-third case of the game's World Edition (Season 3) and also the fifth case to take place in North America.

The Bureau went to Camp Rushmore to inform President James Hewett of SOMBRA's existence while President Hewett consulted foreign dignitaries regarding the conflict between the USNay and USStay movements. Upon reaching the campgrounds, Sidney Hirsch of the Department of Homeland Security informed the team of Special Agent Jonathan Stafford's murder. On Lake Rushmore, Jack and the player found Stafford's body with a bullet wound in his chest.

Mid-investigation, the team stopped everyone from leaving the campgrounds. Later,Agent Riordan of the FBI attempted to take over the investigation, leaving the team with 12 hours to investigate. Moreover, the President denied SOMBRA's existence and went as far as refusing to talk about the organization. The team was able to collect enough evidence to arrest Sidney for the murder.

Initially denying involvement, Sidney admitted that he had shot the man he loved. He said that he was jealous because of Jonathan's affair with First Lady Olivia Hewett and that he had confessed his feelings to him while having lunch. When Jonathan had pushed him away and called him old, Sidney shot him in the chest with his rifle and tried to resuscitate Jonathan after realizing what he had done. Consequently,Judge Adaku sentenced him to 18 years in jail.

Following Sidney's trial, the team tried to convince the President to take SOMBRA's threat seriously. Hewett still refused to talk about SOMBRA, but directed the team to the conference room for a file that the president of Russia had previously given him. Inside a COSMORUSsafebox, they found a pen drive which (per Elliot) contained information about BB, SOMBRA's captured satellite. Elliot thought of retrieving the code that SOMBRA intended to use to hijack all the satellites in the world so the team could show it to the world leaders. In order to retrieve it, the team requested Sidney's help to control BB, having it to land on Earth and pulling the hard drive out of it. During BB's descent, however, someone hijacked the satellite and rerouted it to the Northern Canadian wilderness.

After Carmen helped Sanjay meet his (and Elliot's) idol, Vanna Alabama, the Bureau headed to northern Canada to investigate BB's hijacking.

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