Showing papers by "University of Maryland, Baltimore published in 2017"
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TL;DR: The all-atom additive CHARMM36 protein force field is refinement is presented, with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins.
Abstract: An all-atom protein force field, CHARMM36m, offers improved accuracy for simulating intrinsically disordered peptides and proteins. The all-atom additive CHARMM36 protein force field is widely used in molecular modeling and simulations. We present its refinement, CHARMM36m (
http://mackerell.umaryland.edu/charmm_ff.shtml
), with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins.
3,299 citations
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Florey Institute of Neuroscience and Mental Health1, University of Calgary2, NorthShore University HealthSystem3, University of Michigan4, Boston University5, University of Missouri–Kansas City6, University of Maryland, Baltimore7, University of Washington8, Oslo University Hospital9, University of Zurich10, University of North Carolina at Chapel Hill11, Harvard University12, University of Toronto13, University at Buffalo14, University of Melbourne15, University of California, San Francisco16, Medical College of Wisconsin17, Boston Children's Hospital18, Princeton University19, Vanderbilt University20, Vanderbilt University Medical Center21, Toronto Western Hospital22
TL;DR: This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level, and provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC.
Abstract: The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement.
This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps.
A series of specific clinical questions were developed as part of the consensus process for the Berlin 2016 meeting. Each consensus question was the subject of a specific formal systematic review, which is published concurrently with this summary statement. Readers are directed to these background papers in conjunction with this summary statement as they provide the context for the issues and include the scope of published research, search strategy and citations reviewed for each question. This 2017 consensus statement also summarises each topic and recommendations in the context of all five CISG meetings (that is, 2001, 2004, 2008, 2012 as well as 2016). Approximately 60 000 published articles were screened by the expert panels for the Berlin …
2,388 citations
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Seattle Children's1, Case Western Reserve University2, University of Maryland, Baltimore3, University of Missouri–Kansas City4, Indiana University5, University of Colorado Denver6, Boston Children's Hospital7, University of British Columbia8, Thomas Jefferson University9, American Academy of Pediatrics10, Alfred I. duPont Hospital for Children11, Morehouse College12, Harvard University13, University of Texas Health Science Center at Houston14, University of Pittsburgh15, Columbia University Medical Center16, Cincinnati Children's Hospital Medical Center17
TL;DR: These pediatric hypertension guidelines are an update to the 2004 report and include revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy.
Abstract: These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.
2,082 citations
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Stony Brook University1, University of Minnesota2, University of Notre Dame3, University of Vermont4, University of Toronto5, Boston University6, University of Maryland, Baltimore7, Duke University8, University of Kansas9, King's College London10, Columbia University11, Broad Institute12, Purdue University13, University of Iowa14, University of Georgia15, Texas A&M University16, Oklahoma State University–Stillwater17, University of Groningen18, Florida State University19, Uniformed Services University of the Health Sciences20, Bryn Mawr College21, University of North Texas22, University of Otago23, University at Buffalo24, University of Arizona25, University of New South Wales26, Northwestern University27, Emory University28, University of Kentucky29, University of Pittsburgh30, Brown University31
TL;DR: The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies and provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response.
Abstract: The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record
1,635 citations
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RTI International1, University of Maryland, Baltimore2, University of the West Indies3, University of California, Berkeley4, Harvard University5, Georgia State University6, Brigham and Women's Hospital7, University of Pennsylvania8, American University9, World Bank Group10, University College London11
TL;DR: Recent scientific progress and global commitments to early childhood development are examined, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course.
1,534 citations
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University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, Centers for Disease Control and Prevention11, International Centre for Diarrhoeal Disease Research, Bangladesh12, Tribhuvan University13, University of Bergen14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
1,470 citations
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University of California, San Diego1, Johns Hopkins University2, University of Washington3, University of California, San Francisco4, University of Pennsylvania5, Duke University6, University of Toronto7, New York University8, University of Chicago9, University of Maryland, Baltimore10, University of Paris11, University of Jena12, Victoria University of Wellington13, Brigham Young University14, Primary Children's Hospital15, McGill University16, Kaiser Permanente17, University of Pittsburgh18, Brown University19
TL;DR: An international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care is assembled to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU.
Abstract: Objective:To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU.Methods:We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We a
935 citations
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TL;DR: A second wave of data from the National Institutes of Health Human Microbiome Project is introduced, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals to provide new characterizations of microbiome personalization.
Abstract: The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.
869 citations
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TL;DR: The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
755 citations
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Stanford University1, University of Maryland, Baltimore2, Baylor College of Medicine3, University of Pittsburgh4, University of California, Los Angeles5, College of Osteopathic Medicine of the Pacific6, University of Chicago7, University of Texas at Austin8, Durham University9, University of Alabama10, Society for Women's Health Research11, University of Bologna12, Gannon University13, Brigham and Women's Hospital14, Mayo Clinic15, University of Washington16
TL;DR: There is consensus among experts regarding some indicators of sleep quality among otherwise healthy individuals, but overall, there was less or no consensus regarding sleep architecture or nap‐related variables as elements of good sleep quality.
688 citations
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TL;DR: An updated approach to the diagnosis of idiopathic pulmonary fibrosis is provided, based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society.
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TL;DR: A new framework of targeted immunomodulation after TBI is proposed that incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options and highlights findings that could offer novel therapeutic targets for translational and clinical research.
Abstract: The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration. Our framework incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structuring our discussion around the dynamics of the immune response to TBI - from initial triggers to chronic neuroinflammation - we consider the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration. We summarize both animal model and human studies, with clinical data explicitly defined throughout this Review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including concepts of inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. Moreover, we highlight findings that could offer novel therapeutic targets for translational and clinical research, assimilate evidence from other brain injury models, and identify outstanding questions in the field.
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University of Pittsburgh1, Riley Hospital for Children2, Washington University in St. Louis3, Baylor College of Medicine4, Texas Tech University5, Northwestern University6, University of British Columbia7, Medical College of Wisconsin8, Saint Barnabas Medical Center9, University of Pennsylvania10, University College London11, University of Alberta12, Duke University13, McMaster University14, Yeshiva University15, University of Michigan16, Laval University17, Kaiser Permanente18, Emory University19, University of Maryland, Baltimore20, Cornell University21, Nationwide Children's Hospital22, Children's Mercy Hospital23, Texas Tech University Health Sciences Center at El Paso24, University of Florida25, St Mary's Hospital26, University of Rochester27, University of Washington28, Stanford University29, University of California, San Diego30, Valley Hospital31, University of Melbourne32, Royal Children's Hospital33, Loma Linda University34, Great Ormond Street Hospital35, Boston Children's Hospital36, Austral University37, University of Colorado Denver38, Nemours Foundation39
TL;DR: A major new recommendation in the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock” is consideration of institution—specific use of a recognition bundle containing a trigger tool for rapid identification of patients with septic shock.
Abstract: Objectives:The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Child
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Paris Descartes University1, Cedars-Sinai Medical Center2, University of Alberta3, Johns Hopkins University4, University of Paris5, Autonomous University of Barcelona6, Westmead Hospital7, Harvard University8, University of Texas Medical Branch9, Yeshiva University10, University of Cologne11, Mayo Clinic12, University of Maryland, Baltimore13, Charité14, Leiden University15, University of Manitoba16, Washington University in St. Louis17, NewYork–Presbyterian Hospital18, University of North Carolina at Chapel Hill19, University of Pittsburgh20, University of California, Los Angeles21, Hammersmith Hospital22, Cornell University23, Northwestern University24
TL;DR: Improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification are included.
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TL;DR: Recent observations have shown that CD44 intracellular domain (CD44-ICD) is related to the metastatic potential of breast cancer cells, however, the underlying mechanisms need further elucidation.
Abstract: CD44 is a cell surface adhesion receptor that is highly expressed in many cancers and regulates metastasis via recruitment of CD44 to the cell surface. Its interaction with appropriate extracellular matrix ligands promotes the migration and invasion processes involved in metastases. It was originally identified as a receptor for hyaluronan or hyaluronic acid and later to several other ligands including, osteopontin (OPN), collagens, and matrix metalloproteinases. CD44 has also been identified as a marker for stem cells of several types. Beside standard CD44 (sCD44), variant (vCD44) isoforms of CD44 have been shown to be created by alternate splicing of the mRNA in several cancer. Addition of new exons into the extracellular domain near the transmembrane of sCD44 increases the tendency for expressing larger size vCD44 isoforms. Expression of certain vCD44 isoforms was linked with progression and metastasis of cancer cells as well as patient prognosis. The expression of CD44 isoforms can be correlated with tumor subtypes and be a marker of cancer stem cells. CD44 cleavage, shedding, and elevated levels of soluble CD44 in the serum of patients is a marker of tumor burden and metastasis in several cancers including colon and gastric cancer. Recent observations have shown that CD44 intracellular domain (CD44-ICD) is related to the metastatic potential of breast cancer cells. However, the underlying mechanisms need further elucidation.
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Cleveland Clinic1, University of Ottawa2, Duke University3, Regions Hospital4, University of Tennessee5, Baylor University Medical Center6, Emory University7, University of California, Davis8, University of California, Los Angeles9, Riverside Methodist Hospital10, Northwestern University11, Guy's and St Thomas' NHS Foundation Trust12, University of Pittsburgh13, Yeshiva University14, University of Newcastle15, university of lille16, University of Melbourne17, Lille University of Science and Technology18, University of Helsinki19, University of Maryland, Baltimore20, Harvard University21
TL;DR: Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.
Abstract: BackgroundVasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. MethodsWe randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. ResultsA total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiote...
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Memorial Sloan Kettering Cancer Center1, University of Texas MD Anderson Cancer Center2, University of Minnesota3, University of Denver4, University of California, San Francisco5, Duke University6, Harvard University7, University of Maryland, Baltimore8, Université de Montréal9, Yale University10, Mayo Clinic11
TL;DR: The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.
Abstract: Importance Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. Objective To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non–small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA. Design, Setting, and Participants This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. Main Outcomes and Measures The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. Results The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-molGPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. Conclusions and Relevance In recent years, patient survival and physicians’ ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.
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University of Southern Denmark1, Pfizer2, University of Paris3, University of Zaragoza4, University of East Anglia5, Montreal Heart Institute6, Leiden University Medical Center7, Technische Universität München8, Leiden University9, University of Amsterdam10, University of São Paulo11, University of the Witwatersrand12, Wrocław Medical University13, University of Maryland, Baltimore14, First Faculty of Medicine, Charles University in Prague15, Cleveland Clinic16, University of Manchester17, Auckland City Hospital18, Mayo Clinic19, Charles University in Prague20
TL;DR: In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococzumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the Trial involving higher‐risk Patients.
Abstract: BackgroundBococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. MethodsIn two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10...
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TL;DR: It is concluded that acupuncture is effective for the treatment of chronic pain, with treatment effects persisting over time, and treatment effects persist over time and cannot be explained solely in terms of placebo effects.
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Washington University in St. Louis1, University of Vermont2, National Institutes of Health3, University of Maryland, Baltimore4, University of Pittsburgh5, University of California, San Diego6, University of Utah7, Icahn School of Medicine at Mount Sinai8, McGovern Institute for Brain Research9, SRI International10, University of Michigan11, University of Missouri12
TL;DR: This battery will provide a foundational baseline assessment of the youth’s current function so as to permit characterization of stability and change in key domains over time, and will also be utilized to identify both resilience markers that predict healthy development and risk factors for later adverse outcomes in physical health, mental health, and substance use and abuse.
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TL;DR: Real‐world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials.
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TL;DR: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases, as well as single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.
Abstract: IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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VU University Medical Center1, University of Alberta2, Edith Cowan University3, Netherlands Cancer Institute4, University of South Florida5, Utrecht University6, German Cancer Research Center7, Yale University8, Queensland University of Technology9, University of Maryland, Baltimore10, European University of Madrid11, Maastricht University12, University of Groningen13, University of Amsterdam14, University of Edinburgh15, University of Birmingham16, University of Glasgow17, University of Antwerp18, University of Oslo19, University of Hamburg20, University of Adelaide21, University of Newcastle22, Guy's and St Thomas' NHS Foundation Trust23, University Hospital Heidelberg24, King's College London25, Pennsylvania State University26, Oregon Health & Science University27, Johns Hopkins University28
TL;DR: In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment.
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TL;DR: It is suggested that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195, a randomized, double-blind, placebo-controlled trial in rural Indian newborns.
Abstract: Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.
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Emory University1, Centers for Disease Control and Prevention2, Duke University3, Washington University in St. Louis4, University of British Columbia5, University of Maryland, Baltimore6, Dalhousie University7, Tufts University8, University of Virginia9, Monash University10, Medical University of South Carolina11
TL;DR: These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea and are not intended to replace physician judgement regarding specific patients or clinical or public health situations.
Abstract: These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.
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TL;DR: It is shown that mdivi-1 reversibly inhibits mitochondrial complex I-dependent O2 consumption and reverse electron transfer-mediated reactive oxygen species (ROS) production at concentrations (e.g., 50 μM) used to target mitochondrial fission.
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TL;DR: This guideline summarizes the current recommendations developed by the SIS task force on the treatment of patients who have IAI regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy.
Abstract: Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the t...
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University of Pennsylvania1, Cleveland Clinic2, University of California, Los Angeles3, Vanderbilt University Medical Center4, University of Pittsburgh5, University of Minnesota6, University of Alabama7, Indiana University8, Baylor University9, Texas A&M Health Science Center College of Medicine10, Cedars-Sinai Medical Center11, Columbia University Medical Center12, University of Maryland, Baltimore13, Washington University in St. Louis14
TL;DR: Donor-derived cell-free DNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejected.
Abstract: Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P 1% indicate a probability of active rejection.
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TL;DR: A baseline investigation of variability in taxonomic profiling for the Microbiome Quality Control project baseline study finds variations depended most on biospecimen type and origin, followed by DNA extraction, sample handling environment, and bioinformatics.
Abstract: In order for human microbiome studies to translate into actionable outcomes for health, meta-analysis of reproducible data from population-scale cohorts is needed. Achieving sufficient reproducibility in microbiome research has proven challenging. We report a baseline investigation of variability in taxonomic profiling for the Microbiome Quality Control (MBQC) project baseline study (MBQC-base). Blinded specimen sets from human stool, chemostats, and artificial microbial communities were sequenced by 15 laboratories and analyzed using nine bioinformatics protocols. Variability depended most on biospecimen type and origin, followed by DNA extraction, sample handling environment, and bioinformatics. Analysis of artificial community specimens revealed differences in extraction efficiency and bioinformatic classification. These results may guide researchers in experimental design choices for gut microbiome studies.
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New York University1, Rutgers University2, University of Paris3, University of California, Berkeley4, University of California, San Francisco5, University of Michigan6, National Institutes of Health7, Umeå University8, University of Rochester Medical Center9, Queen Mary University of London10, Utrecht University11, National Institute for Health Research12, University of Basel13, Swiss Tropical and Public Health Institute14, University of Maryland, Baltimore15, University of California, Los Angeles16, University of Southern California17, Aarhus University18, Pompeu Fabra University19
TL;DR: A set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health are proposed.
Abstract: The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.