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Showing papers on "Population published in 2014"


Journal ArticleDOI
TL;DR: The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years.
Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data were collected by the National Center for Health Statistics. A total of 1,665,540 new cancer cases and 585,720 cancer deaths are projected to occur in the United States in 2014. During the most recent 5 years for which there are data (2006-2010), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.4% per year in women. The combined cancer death rate (deaths per 100,000 population) has been continuously declining for 2 decades, from a peak of 215.1 in 1991 to 171.8 in 2010. This 20% decline translates to the avoidance of approximately 1,340,400 cancer deaths (952,700 among men and 387,700 among women) during this time period. The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years. Notably, black men experienced the largest drop within every 10-year age group. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population.

10,829 citations


Journal ArticleDOI
05 Feb 2014-JAMA
TL;DR: Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
Abstract: Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

7,119 citations


Journal ArticleDOI
TL;DR: The global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glauComa (PACG) and the number of affected people in 2020 and 2040 are examined, disproportionally affecting people residing in Asia and Africa.

4,318 citations


Journal ArticleDOI
TL;DR: A reference-point-based many-objective evolutionary algorithm that emphasizes population members that are nondominated, yet close to a set of supplied reference points is suggested that is found to produce satisfactory results on all problems considered in this paper.
Abstract: Having developed multiobjective optimization algorithms using evolutionary optimization methods and demonstrated their niche on various practical problems involving mostly two and three objectives, there is now a growing need for developing evolutionary multiobjective optimization (EMO) algorithms for handling many-objective (having four or more objectives) optimization problems. In this paper, we recognize a few recent efforts and discuss a number of viable directions for developing a potential EMO algorithm for solving many-objective optimization problems. Thereafter, we suggest a reference-point-based many-objective evolutionary algorithm following NSGA-II framework (we call it NSGA-III) that emphasizes population members that are nondominated, yet close to a set of supplied reference points. The proposed NSGA-III is applied to a number of many-objective test problems with three to 15 objectives and compared with two versions of a recently suggested EMO algorithm (MOEA/D). While each of the two MOEA/D methods works well on different classes of problems, the proposed NSGA-III is found to produce satisfactory results on all problems considered in this paper. This paper presents results on unconstrained problems, and the sequel paper considers constrained and other specialties in handling many-objective optimization problems.

3,906 citations


Journal ArticleDOI
TL;DR: Evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010 is provided, with significant public health implications.
Abstract: Background— The global burden of atrial fibrillation (AF) is unknown. Methods and Results— We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. Conclusions— These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.

3,443 citations


Journal ArticleDOI
TL;DR: In this article, the authors did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013, using retinal photographs and standardised grading classifications.

3,062 citations


Journal ArticleDOI
TL;DR: The AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarc Openia intervention studies and the implementation of sarcopenian in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.

2,976 citations


Journal ArticleDOI
25 Jul 2014-Science
TL;DR: Defaunation is both a pervasive component of the planet’s sixth mass extinction and also a major driver of global ecological change.
Abstract: We live amid a global wave of anthropogenically driven biodiversity loss: species and population extirpations and, critically, declines in local species abundance. Particularly, human impacts on animal biodiversity are an under-recognized form of global environmental change. Among terrestrial vertebrates, 322 species have become extinct since 1500, and populations of the remaining species show 25% average decline in abundance. Invertebrate patterns are equally dire: 67% of monitored populations show 45% mean abundance decline. Such animal declines will cascade onto ecosystem functioning and human well-being. Much remains unknown about this “Anthropocene defaunation”; these knowledge gaps hinder our capacity to predict and limit defaunation impacts. Clearly, however, defaunation is both a pervasive component of the planet’s sixth mass extinction and also a major driver of global ecological change.

2,697 citations


Journal ArticleDOI
TL;DR: In this article, the global burden of hip and knee OA was estimated as part of the Global Burden of Disease 2010 study and the burden of OA compared with other conditions.
Abstract: Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world9s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.

2,440 citations


Journal ArticleDOI
TL;DR: The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment, and current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER‐Medicare linked databases.
Abstract: The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship.

2,383 citations


Journal ArticleDOI
TL;DR: Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations, including the most current data on incidence, survival, and mortality rates and trends.
Abstract: Colorectal cancer is the third most common cancer and the third leading cause of cancer death in men and women in the United States. This article provides an overview of colorectal cancer statistics, including the most current data on incidence, survival, and mortality rates and trends. Incidence data were provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results program and the North American Association of Central Cancer Registries. Mortality data were provided by the National Center for Health Statistics. In 2014, an estimated 71,830 men and 65,000 women will be diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease. Greater than one-third of all deaths (29% in men and 43% in women) will occur in individuals aged 80 years and older. There is substantial variation in tumor location by age. For example, 26% of colorectal cancers in women aged younger than 50 years occur in the proximal colon, compared with 56% of cases in women aged 80 years and older. Incidence and death rates are highest in blacks and lowest in Asians/Pacific Islanders; among males during 2006 through 2010, death rates in blacks (29.4 per 100,000 population) were more than double those in Asians/Pacific Islanders (13.1) and 50% higher than those in non-Hispanic whites (19.2). Overall, incidence rates decreased by approximately 3% per year during the past decade (2001-2010). Notably, the largest drops occurred in adults aged 65 and older. For instance, rates for tumors located in the distal colon decreased by more than 5% per year. In contrast, rates increased during this time period among adults younger than 50 years. Colorectal cancer death rates declined by approximately 2% per year during the 1990s and by approximately 3% per year during the past decade. Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations.

Journal ArticleDOI
06 Nov 2014-Cell
TL;DR: Compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, many microbial taxa whose abundances were influenced by host genetics were identified.

Journal ArticleDOI
TL;DR: The methodological advances in epidemiology have facilitated the use of the Danish Civil Registration System (CRS) in ways not previously described systematically, and it is concluded that the CRS is a key tool for epidemiological research in Denmark.
Abstract: The methodological advances in epidemiology have facilitated the use of the Danish Civil Registration System (CRS) in ways not previously described systematically. We reviewed the CRS and its use as a research tool in epidemiology. We obtained information from the Danish Law on Civil Registration and the Central Office of Civil Registration, and used existing literature to provide illustrative examples of its use. The CRS is an administrative register established on April 2, 1968. It contains individual-level information on all persons residing in Denmark (and Greenland as of May 1, 1972). By January 2014, the CRS had cumulatively registered 9.5 million individuals and more than 400 million person-years of follow-up. A unique ten-digit Civil Personal Register number assigned to all persons in the CRS allows for technically easy, cost-effective, and unambiguous individual-level record linkage of Danish registers. Daily updated information on migration and vital status allows for nationwide cohort studies with virtually complete long-term follow-up on emigration and death. The CRS facilitates sampling of general population comparison cohorts, controls in case–control studies, family cohorts, and target groups in population surveys. The data in the CRS are virtually complete, have high accuracy, and can be retrieved for research purposes while protecting the anonymity of Danish residents. In conclusion, the CRS is a key tool for epidemiological research in Denmark.

Journal ArticleDOI
TL;DR: The newly recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings and includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain- related TMD.
Abstract: Temporomandibular disorders (TMD) are a significant public health problem affecting approximately 5% to 12% of the population.1 TMD is the second most common musculoskeletal condition (after chronic low back pain) resulting in pain and disability.1 Pain-related TMD can impact the individual's daily activities, psychosocial functioning, and quality of life. Overall, the annual TMD management cost in the USA, not including imaging, has doubled in the last decade to $4 billion.1 Patients often seek consultation with dentists for their TMD, especially for pain-related TMD. Diagnostic criteria for TMD with simple, clear, reliable, and valid operational definitions for the history, examination, and imaging procedures are needed to render physical diagnoses in both clinical and research settings. In addition, biobehavioral assessment of pain-related behavior and psychosocial functioning—an essential part of the diagnostic process—is required and provides the minimal information whereby one can determine whether the patient's pain disorder, especially when chronic, warrants further multidisciplinary assessment. Taken together, a new dual-axis Diagnostic Criteria for TMD (DC/TMD) will provide evidence-based criteria for the clinician to use when assessing patients, and will facilitate communication regarding consultations, referrals, and prognosis.2 The research community benefits from the ability to use well-defined and clinically relevant characteristics associated with the phenotype in order to facilitate more generalizable research. When clinicians and researchers use the same criteria, taxonomy, and nomenclature, then clinical questions and experience can be more easily transferred into relevant research questions, and research findings are more accessible to clinicians to better diagnose and manage their patients. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) have been the most widely employed diagnostic protocol for TMD research since its publication in 1992.3 This classification system was based on the biopsychosocial model of pain4 that included an Axis I physical assessment, using reliable and well-operationalized diagnostic criteria, and an Axis II assessment of psychosocial status and pain-related disability. The intent was to simultaneously provide a physical diagnosis and identify other relevant characteristics of the patient that could influence the expression and thus management of their TMD. Indeed, the longer the pain persists, the greater the potential for emergence and amplification of cognitive, psychosocial, and behavioral risk factors, with resultant enhanced pain sensitivity, greater likelihood of additional pain persistence, and reduced probability of success from standard treatments.5 The RDC/TMD (1992) was intended to be only a first step toward improved TMD classification, and the authors stated the need for future investigation of the accuracy of the Axis I diagnostic algorithms in terms of reliability and criterion validity—the latter involving the use of credible reference standard diagnoses. Also recommended was further assessment of the clinical utility of the Axis II instruments. The original RDC/TMD Axis I physical diagnoses have content validity based on the critical review by experts of the published diagnostic approach in use at that time and were tested using population-based epidemiologic data.6 Subsequently, a multicenter study showed that, for the most common TMD, the original RDC/TMD diagnoses exhibited sufficient reliability for clinical use.7 While the validity of the individual RDC/TMD diagnoses has been extensively investigated, assessment of the criterion validity for the complete spectrum of RDC/TMD diagnoses had been absent until recently.8 For the original RDC/TMD Axis II instruments, good evidence for their reliability and validity for measuring psychosocial status and pain-related disability already existed when the classification system was published.9–13 Subsequently, a variety of studies have demonstrated the significance and utility of the original RDC/TMD biobehavioral measures in such areas as predicting outcomes of clinical trials, escalation from acute to chronic pain, and experimental laboratory settings.14–20 Other studies have shown that the original RDC/TMD biobehavioral measures are incomplete in terms of prediction of disease course.21–23 The overall utility of the biobehavioral measures in routine clinical settings has, however, yet to be demonstrated, in part because most studies have to date focused on Axis I diagnoses rather than Axis II biobehavioral factors.24 The aims of this article are to present the evidence-based new Axis I and Axis II DC/TMD to be used in both clinical and research settings, as well as present the processes related to their development.

Journal ArticleDOI
TL;DR: LBP causes more global disability than any other condition and with the ageing population, there is an urgent need for further research to better understand LBP across different settings.
Abstract: Supported by the Bill and Melinda Gates Foundation (to Dr Hoy and Prof Vos), the Australian Commonwealth Department of Health and Ageing (to Dr Smith (University of Sydney, Institute of Bone and Joint Research) and Prof March), the Australian National Health and Medical Research Council (Postgraduate Scholarship 569772 to Dr Hoy and Practitioner Fellowships 334010 (2005–2009) and 606429 (2010–2014) to Prof Buchbinder, and the Ageing and Alzheimers Research Foundation (Asst Prof Blyth).

Journal ArticleDOI
TL;DR: A unique placental microbiome niche was characterized, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericute, Proteobacteria, Bacteroidetes, and Fusobacteria phyla, which was consistently different from those reported in other parts of the body, including the skin and urogenital tract.
Abstract: Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001).

Journal ArticleDOI
04 Mar 2014-PeerJ
TL;DR: The R package poppr is developed providing unique tools for analysis of data from admixed, clonal, mixed, and/or sexual populations, and functions for genotypic diversity and clone censoring are specific for clonal populations.
Abstract: Many microbial, fungal, or oomcyete populations violate assumptions for population genetic analysis because these populations are clonal, admixed, partially clonal, and/or sexual. Furthermore, few tools exist that are specifically designed for analyzing data from clonal populations, making analysis difficult and haphazard. We developed the R package poppr providing unique tools for analysis of data from admixed, clonal, mixed, and/or sexual populations. Currently, poppr can be used for dominant/codominant and haploid/diploid genetic data. Data can be imported from several formats including GenAlEx formatted text files and can be analyzed on a user-defined hierarchy that includes unlimited levels of subpopulation structure and clone censoring. New functions include calculation of Bruvo’s distance for microsatellites, batch-analysis of the index of association with several indices of genotypic diversity, and graphing including dendrograms with bootstrap support and minimum spanning networks. While functions for genotypic diversity and clone censoring are specific for clonal populations, several functions found in poppr are also valuable to analysis of any populations. A manual with documentation and examples is provided. Poppr is open source and major releases are available on CRAN: http://cran.r-project.org/package=poppr. More supporting documentation and tutorials can be found under ‘resources’ at: http://grunwaldlab.cgrb.oregonstate.edu/.

Journal ArticleDOI
TL;DR: An overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening is provided, with African American women having the poorest breast cancer survival of any racial/ethnic group.
Abstract: In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor-positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor-negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.

Journal ArticleDOI
Andrew R. Wood1, Tõnu Esko2, Jian Yang3, Sailaja Vedantam4  +441 moreInstitutions (132)
TL;DR: This article identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height, and all common variants together captured 60% of heritability.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Journal ArticleDOI
TL;DR: This guideline addresses the wide array of SSTIs that occur in this population and emphasizes the importance of clinical skills in promptly diagnosing SSTI, identifying the pathogen, and administering effective treatments in a timely fashion.
Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

Journal ArticleDOI
TL;DR: Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa, and watchful waiting is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy.

Journal ArticleDOI
TL;DR: Despite a substantial degree of inter-survey heterogeneity in the meta-analysis, the findings confirm that common mental disorders are highly prevalent globally, affecting people across all regions of the world.
Abstract: Background: Since the introduction of specified diagnostic criteria for mental disorders in the 1970s, there has been a rapid expansion in the number of large-scale mental health surveys providing population estimates of the combined prevalence of common mental disorders (most commonly involving mood, anxiety and substance use disorders). In this study we undertake a systematic review and meta-analysis of this literature. Methods: We applied an optimized search strategy across the Medline, PsycINFO, EMBASE and PubMed databases, supplemented by hand searching to identify relevant surveys. We identified 174 surveys across 63 countries providing period prevalence estimates (155 surveys) and lifetime prevalence estimates (85 surveys). Random effects meta-analysis was undertaken on logit-transformed prevalence rates to calculate pooled prevalence estimates, stratified according to methodological and substantive groupings. Results: Pooling across all studies, approximately 1 in 5 respondents (17.6%, 95% confidence interval:16.3–18.9%) were identified as meeting criteria for a common mental disorder during the 12-months preceding assessment; 29.2% (25.9–32.6%) of respondents were identified as having experienced a common mental disorder at some time during their lifetimes. A consistent gender effect in the prevalence of common mental disorder was evident; women having higher rates of mood (7.3%:4.0%) and anxiety (8.7%:4.3%) disorders during the previous 12 months and men having higher rates of substance use disorders (2.0%:7.5%), with a similar pattern for lifetime prevalence. There was also evidence of consistent regional variation in the prevalence of common mental disorder. Countries within North and South East Asia in particular displayed consistently lower one-year and lifetime prevalence estimates than other regions. One-year prevalence rates were also low among Sub-Saharan-Africa, whereas English speaking counties returned the highest lifetime prevalence estimates. Conclusions: Despite a substantial degree of inter-survey heterogeneity in the meta-analysis, the findings confirm that common mental disorders are highly prevalent globally, affecting people across all regions of the world. This research provides an important resource for modelling population needs based on global regional estimates of mental disorder. The reasons for regional variation in mental disorder require further investigation.

Journal ArticleDOI
TL;DR: A multithreaded program suite called ANGSD that can calculate various summary statistics, and perform association mapping and population genetic analyses utilizing the full information in next generation sequencing data by working directly on the raw sequencing data or by using genotype likelihoods.
Abstract: High-throughput DNA sequencing technologies are generating vast amounts of data. Fast, flexible and memory efficient implementations are needed in order to facilitate analyses of thousands of samples simultaneously. We present a multithreaded program suite called ANGSD. This program can calculate various summary statistics, and perform association mapping and population genetic analyses utilizing the full information in next generation sequencing data by working directly on the raw sequencing data or by using genotype likelihoods. The open source c/c++ program ANGSD is available at http://www.popgen.dk/angsd . The program is tested and validated on GNU/Linux systems. The program facilitates multiple input formats including BAM and imputed beagle genotype probability files. The program allow the user to choose between combinations of existing methods and can perform analysis that is not implemented elsewhere.

Journal ArticleDOI
TL;DR: Estimates of the number of new cancer cases and deaths for children and adolescents in the United States are provided and an overview of risk factors, symptoms, treatment, and long‐term and late effects for common pediatric cancers are provided.
Abstract: In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high-quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow-up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long-term and late effects for common pediatric cancers.

Journal ArticleDOI
TL;DR: The characteristics of 3D cell culture systems in comparison to the two-dimensional monolayer culture are discussed, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles.
Abstract: Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

Journal ArticleDOI
TL;DR: In this paper, the authors present an assessment of a rapidly growing body of economic research on financial literacy and examine the impact of financial literacy on economic decision-making in the United States and elsewhere.
Abstract: This paper undertakes an assessment of a rapidly growing body of economic research on financial literacy. We start with an overview of theoretical research, which casts financial knowledge as a form of investment in human capital. Endogenizing financial knowledge has important implications for welfare, as well as policies intended to enhance levels of financial knowledge in the larger population. Next, we draw on recent surveys to establish how much (or how little) people know and identify the least financially savvy population subgroups. This is followed by an examination of the impact of financial literacy on economic decision making in the United States and elsewhere. While the literature is still young, conclusions may be drawn about the effects and consequences of financial illiteracy and what works to remedy these gaps. A final section offers thoughts on what remains to be learned if researchers are to better inform theoretical and empirical models as well as public policy. (JEL A20, D14, G11, I20, J26)

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TL;DR: TIDE, a method that requires only a pair of PCR reactions and two standard capillary sequencing runs to identify the major induced mutations in the projected editing site and accurately determines their frequency in a cell population, is presented.
Abstract: The efficacy and the mutation spectrum of genome editing methods can vary substantially depending on the targeted sequence. A simple, quick assay to accurately characterize and quantify the induced mutations is therefore needed. Here we present TIDE, a method for this purpose that requires only a pair of PCR reactions and two standard capillary sequencing runs. The sequence traces are then analyzed by a specially developed decomposition algorithm that identifies the major induced mutations in the projected editing site and accurately determines their frequency in a cell population. This method is cost-effective and quick, and it provides much more detailed information than current enzyme-based assays. An interactive web tool for automated decomposition of the sequence traces is available. TIDE greatly facilitates the testing and rational design of genome editing strategies.

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TL;DR: Afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC and should be considered as a first-line treatment option for this patient population.
Abstract: Summary Background Afatinib—an oral irreversible ErbB family blocker—improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin—a chemotherapy regimen widely used in Asia—for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. Methods This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0–1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m 2 on day 1 and day 8 plus cisplatin 75 mg/m 2 on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393. Findings 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7–13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1–6·7; hazard ratio 0·28, 95% CI 0·20–0·39; p Interpretation First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. Funding Boehringer Ingelheim.

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02 Jan 2014-Nature
TL;DR: It is shown that interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene and a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans is established.
Abstract: We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

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TL;DR: This review provides summary of literature related to the syndrome's definition, epidemiology, underlying pathogenesis, and treatment approaches of each of the risk factors comprising metabolic syndrome.
Abstract: Metabolic syndrome is defined by a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all cause mortality. Insulin resistance, visceral adiposity, atherogenic dyslipidemia, endothelial dysfunction, genetic susceptibility, elevated blood pressure, hypercoagulable state, and chronic stress are the several factors which constitute the syndrome. Chronic inflammation is known to be associated with visceral obesity and insulin resistance which is characterized by production of abnormal adipocytokines such as tumor necrosis factor α , interleukin-1 (IL-1), IL-6, leptin, and adiponectin. The interaction between components of the clinical phenotype of the syndrome with its biological phenotype (insulin resistance, dyslipidemia, etc.) contributes to the development of a proinflammatory state and further a chronic, subclinical vascular inflammation which modulates and results in atherosclerotic processes. Lifestyle modification remains the initial intervention of choice for such population. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioural strategies. Pharmacological treatment should be considered for those whose risk factors are not adequately reduced with lifestyle changes. This review provides summary of literature related to the syndrome's definition, epidemiology, underlying pathogenesis, and treatment approaches of each of the risk factors comprising metabolic syndrome.