Showing papers by "Boston Children's Hospital published in 2015"
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
17,834 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
TL;DR: Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together.
5,506 citations
01 May 2015
TL;DR: Drop-seq as discussed by the authors analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin, and identifies 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes.
Abstract: Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. VIDEO ABSTRACT.
3,365 citations
Baylor College of Medicine1, Stanford University2, University of Pittsburgh3, University of California, Los Angeles4, Sapienza University of Rome5, Loyola University Chicago6, University of Texas at Austin7, University of Texas Southwestern Medical Center8, Boston Children's Hospital9, University of Chicago10, Johns Hopkins University School of Medicine11, Georgetown University12, University of Toronto13, Gannon University14, American Academy of Pediatrics15, University of Louisville16, University of Washington17, Eastern Virginia Medical School18
TL;DR: A scientifically rigorous update to the National Sleep Foundation's sleep duration recommendations, determined expert recommendations for sufficient sleep durations across the lifespan using the RAND/UCLA Appropriateness Method.
2,568 citations
Boston Children's Hospital1, Harvard University2, King's College London3, Lund University4, Massachusetts Eye and Ear Infirmary5, University of São Paulo6, University of California, San Diego7, Imperial College London8, Partners In Health9, Brigham and Women's Hospital10, Royal North Shore Hospital11, Medical College of Wisconsin12, Nanyang Technological University13, Monash University14, University of Sierra Leone15, University of Oxford16, Mongolian National University17, University of Malawi18, Flinders University19, Beth Israel Deaconess Medical Center20, Bhabha Atomic Research Centre21, Royal Australasian College of Surgeons22, Stanford University23, University of California, San Francisco24
TL;DR: The need for surgical services in low- and middleincome countries will continue to rise substantially from now until 2030, with a large projected increase in the incidence of cancer, road traffic injuries, and cardiovascular and metabolic diseases in LMICs.
2,209 citations
University of Amsterdam1, Utrecht University2, University of Virginia3, Brown University4, Bond University5, University of Sydney6, University of Ottawa7, Ottawa Hospital Research Institute8, University of California, San Francisco9, VU University Medical Center10, Beth Israel Deaconess Medical Center11, Boston Children's Hospital12, Northwestern University13, University of Oxford14, Paris Descartes University15
TL;DR: STARD 2015 is presented, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study, which incorporates recent evidence about sources of bias and variability in diagnostic accuracy.
Abstract: Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting Diagnostic Accuracy (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
2,116 citations
TL;DR: Global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic, highlighting the importance of miRNA dysregulation in cancer.
Abstract: MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and overexpression of individual 'oncomiRs' or genetic loss of tumour suppressor miRNAs are associated with human cancer and are sufficient to drive tumorigenesis in mouse models. Furthermore, global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic. This, together with the recent identification of novel miRNA regulatory factors and pathways, highlights the importance of miRNA dysregulation in cancer.
1,659 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
TL;DR: The results suggest that itching during inflammatory skin diseases such as atopic dermatitis is linked to a distinct itch-generating type, and demonstrate single-cell RNA-seq as an effective strategy for dissecting sensory responsive cells into distinct neuronal types.
Abstract: The primary sensory system requires the integrated function of multiple cell types, although its full complexity remains unclear. We used comprehensive transcriptome analysis of 622 single mouse neurons to classify them in an unbiased manner, independent of any a priori knowledge of sensory subtypes. Our results reveal eleven types: three distinct low-threshold mechanoreceptive neurons, two proprioceptive, and six principal types of thermosensitive, itch sensitive, type C low-threshold mechanosensitive and nociceptive neurons with markedly different molecular and operational properties. Confirming previously anticipated major neuronal types, our results also classify and provide markers for new, functionally distinct subtypes. For example, our results suggest that itching during inflammatory skin diseases such as atopic dermatitis is linked to a distinct itch-generating type. We demonstrate single-cell RNA-seq as an effective strategy for dissecting sensory responsive cells into distinct neuronal types. The resulting catalog illustrates the diversity of sensory types and the cellular complexity underlying somatic sensation.
1,609 citations
Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
TL;DR: These data show that lumacaftor in combination with ivacaftors provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation.
Abstract: A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV 1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor–ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV 1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor–ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor–ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor–ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor–ivacaftor versus 1.6% among those who received placebo. CONCLUSIONS These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.)
TL;DR: BOLT-LMM is presented, which requires only a small number of O(MN) time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes.
Abstract: Linear mixed models are a powerful statistical tool for identifying genetic associations and avoiding confounding. However, existing methods are computationally intractable in large cohorts and may not optimize power. All existing methods require time cost O(MN(2)) (where N is the number of samples and M is the number of SNPs) and implicitly assume an infinitesimal genetic architecture in which effect sizes are normally distributed, which can limit power. Here we present a far more efficient mixed-model association method, BOLT-LMM, which requires only a small number of O(MN) time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes. We applied BOLT-LMM to 9 quantitative traits in 23,294 samples from the Women's Genome Health Study (WGHS) and observed significant increases in power, consistent with simulations. Theory and simulations show that the boost in power increases with cohort size, making BOLT-LMM appealing for genome-wide association studies in large cohorts.
TL;DR: The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment and a detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented.
Abstract: The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively.
Baylor College of Medicine1, Stanford University2, University of Pittsburgh3, University of California, Los Angeles4, Sapienza University of Rome5, Loyola University Chicago6, University of Texas at Austin7, University of Texas Southwestern Medical Center8, Boston Children's Hospital9, University of Chicago10, Johns Hopkins University School of Medicine11, Georgetown University12, University of Toronto13, Gannon University14, American Academy of Pediatrics15, University of Louisville16, University of Washington17, Eastern Virginia Medical School18
TL;DR: Consensus using a multidisciplinary expert Panel lends robust credibility to the results and the self-designated basis for duration selection and critical discussions are provided.
Utrecht University1, University of Florida2, Australian National University3, University of Zurich4, Technical University of Denmark5, Institute of Tropical Medicine Antwerp6, Boston Children's Hospital7, University of Kelaniya8, Université catholique de Louvain9, World Health Organization10, Centers for Disease Control and Prevention11
TL;DR: The Foodborne Disease Burden Epidemiology Reference Group (FERG) reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards, finding that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis.
Abstract: Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old-although they represent only 9% of the global population-and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels.
TL;DR: This review highlights aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol.
Abstract: Receptors of the innate immune system detect conserved determinants of microbial and viral origin. Activation of these receptors initiates signaling events that culminate in an effective immune response. Recently, the view that innate immune signaling events rely on and operate within a complex cellular infrastructure has become an important framework for understanding the regulation of innate immunity. Compartmentalization within this infrastructure provides the cell with the ability to assign spatial information to microbial detection and regulate immune responses. Several cell biological processes play a role in the regulation of innate signaling responses; at the same time, innate signaling can engage cellular processes as a form of defense or to promote immunological memory. In this review, we highlight these aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol.
TL;DR: The similarities and differences between these two classes of vesicle are reviewed, suggesting that, despite their considerable differences, the functions of ectosomes may be largely analogous to those of exosomes.
TL;DR: Biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor.
Abstract: Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor.
Paris Diderot University1, Lenox Hill Hospital2, University of Cincinnati3, Boston Children's Hospital4, Medical College of Wisconsin5, University of California, San Francisco6, Columbia University7, Johns Hopkins University8, Université de Montréal9, University of British Columbia10, Cliniques Universitaires Saint-Luc11
TL;DR: The updated official ISSVA classification of vascular anomalies is presented, acknowledging that it will require modification as new scientific information becomes available.
Abstract: Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists. Classification schemes provide a consistent terminology and serve as a guide for pathologists, clinicians, and researchers. One of the goals of the International Society for the Study of Vascular Anomalies (ISSVA) is to achieve a uniform classification. The last classification (1997) stratified vascular lesions into vascular malformations and proliferative vascular lesions (tumors). However, additional disease entities have since been identified that are complex and less easily classified by generic headings, such as capillary malformation, venous malformation, lymphatic malformation, etc. We hereby present the updated official ISSVA classification of vascular anomalies. The general biological scheme of the classification is retained. The section on tumors has been expanded and lists the main recognized vascular tumors, classified as benign, locally aggressive or borderline, and malignant. A list of well-defined diseases is included under each generic heading in the "Simple Vascular Malformations" section. A short definition is added for eponyms. Two new sections were created: one dealing with the malformations of individually named vessels (previously referred to as "truncular" malformations); the second groups lesions of uncertain or debated nature (tumor versus malformation). The known genetic defects underlying vascular anomalies are included in an appendix. This classification is meant to be a framework, acknowledging that it will require modification as new scientific information becomes available.
Columbia University1, University of Southern California2, University of California, San Diego3, University of California, Davis4, Cornell University5, The Queen's Medical Center6, University of Massachusetts Medical School7, Yale University8, Kennedy Krieger Institute9, Boston Children's Hospital10, Harvard University11
TL;DR: Investigation of relationships between socioeconomic factors and brain morphometry among a cohort of typically developing individuals suggests that income relates most strongly to brain structure among the most disadvantaged children.
Abstract: Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.
German Cancer Research Center1, Boston Children's Hospital2, University of Texas MD Anderson Cancer Center3, St. Jude Children's Research Hospital4, University of Toronto5, Max Planck Society6, Heidelberg University7, University of Utah8, Tel Aviv University9, University of Colorado Denver10, University of Bern11, Masaryk University12, University of Texas Health Science Center at San Antonio13, University of California, San Francisco14, New York University15, University of Cambridge16, University of Hamburg17, University of Bonn18
TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
Necker-Enfants Malades Hospital1, Kuwait University2, Boston Children's Hospital3, Rockefeller University4, Icahn School of Medicine at Mount Sinai5, National Institutes of Health6, Ludwig Maximilian University of Munich7, National Defense Medical College8, Seattle Children's Research Institute9, Paris Diderot University10, University of California, San Francisco11, Children's Hospital of Philadelphia12, University of Melbourne13, Royal Children's Hospital14, University of Antioquia15, UCL Institute of Child Health16
TL;DR: The most up-to-date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
Abstract: We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
TL;DR: It is shown that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis), and wound healing was accelerated in Padi4−/− mice as compared to WT mice, and it was not compromised by diabetes.
Abstract: Wound healing is impaired in diabetes, resulting in significant morbidity and mortality. Neutrophils are the main leukocytes involved in the early phase of healing. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs, however, can also induce tissue damage. Here we show that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis). Expression of peptidylarginine deiminase 4 (PAD4, encoded by Padi4 in mice), an enzyme important in chromatin decondensation, was elevated in neutrophils from individuals with diabetes. When subjected to excisional skin wounds, wild-type (WT) mice produced large quantities of NETs in wounds, but this was not observed in Padi4(-/-) mice. In diabetic mice, higher levels of citrullinated histone H3 (H3Cit, a NET marker) were found in their wounds than in normoglycemic mice and healing was delayed. Wound healing was accelerated in Padi4(-/-) mice as compared to WT mice, and it was not compromised by diabetes. DNase 1, which disrupts NETs, accelerated wound healing in diabetic and normoglycemic WT mice. Thus, NETs impair wound healing, particularly in diabetes, in which neutrophils are more susceptible to NETosis. Inhibiting NETosis or cleaving NETs may improve wound healing and reduce NET-driven chronic inflammation in diabetes.
TL;DR: DEPICT as mentioned in this paper is an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated locis are highly expressed.
Abstract: The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.
University of Utah1, Baylor College of Medicine2, University of North Carolina at Chapel Hill3, National Institutes of Health4, University of Toronto5, Boston Children's Hospital6, Johns Hopkins University7, Stanford University8, Cincinnati Children's Hospital Medical Center9, University of Pennsylvania10, Seattle Children's11, American Society of Human Genetics12
TL;DR: This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children and a broad range of test technologies and their applications in clinical medicine and research.
Abstract: In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education.
Boston Children's Hospital1, NewYork–Presbyterian Hospital2, University of Chicago3, University of Chile4, Ohio State University5, University of Barcelona6, University of Adelaide7, Georgetown University8, Baylor College of Medicine9, American University of Beirut10, University of Pittsburgh11, Sanjay Gandhi Post Graduate Institute of Medical Sciences12
TL;DR: While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.
Abstract: Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological feat
Harvard University1, University of South Florida2, University of Washington3, University of British Columbia4, University of Ottawa5, Boston Children's Hospital6, Christiana Care Health System7, University of Minnesota8, University of Vermont9, Washington University in St. Louis10, Food and Drug Administration11, Wayne State University12, University of Pennsylvania13, Englewood Hospital and Medical Center14, Yale University15, Canadian Blood Services16, University of Massachusetts Medical School17, University of Texas Southwestern Medical Center18, Johns Hopkins University19, Children's National Medical Center20
TL;DR: These guidelines were designed to provide pragmatic recommendations, based on the best available published evidence, about when platelet transfusion may be appropriate in adult patients, and provide advice for adult patients who are candidates for platelets transfusion.
Abstract: Platelet transfusions are administered to prevent or treat bleeding in patients with quantitative or qualitative platelet disorders The AABB (formerly, the American Association of Blood Banks) dev
TL;DR: The insights gained from sequencing the whole genomes of Icelanders to a median depth of 20× provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.
Abstract: Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.
Woolcock Institute of Medical Research1, University of Cape Town2, University of Manitoba3, Laval University4, Federal University of Bahia5, Harvard University6, Helsinki University Central Hospital7, Kagoshima University8, Erasmus University Rotterdam9, University of Wisconsin-Madison10, McMaster University11, University of Pisa12, University of Southern Denmark13, Universidade Federal de Santa Catarina14, University of Costa Rica15, Boston Children's Hospital16, The Chinese University of Hong Kong17, University of British Columbia18
TL;DR: The changes include a revised asthma definition, tools for assessing symptom control and risk factors for adverse outcomes, and updated strategies for adaptation and implementation of GINA recommendations.
Abstract: Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma-chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.