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Journal ArticleDOI
TL;DR: Overall improvements to speed and scalability are accompanied by specific enhancements that support complex interactive queries on large track sets.
Abstract: JBrowse is a fast and full-featured genome browser built with JavaScript and HTML5. It is easily embedded into websites or apps but can also be served as a standalone web page. Overall improvements to speed and scalability are accompanied by specific enhancements that support complex interactive queries on large track sets. Analysis functions can readily be added using the plugin framework; most visual aspects of tracks can also be customized, along with clicks, mouseovers, menus, and popup boxes. JBrowse can also be used to browse local annotation files offline and to generate high-resolution figures for publication. JBrowse is a mature web application suitable for genome visualization and analysis.

605 citations


Journal ArticleDOI
TL;DR: It is shown that human movement patterns explain the spread of both Aedes aegypti and Aedes albopictus in Europe and the United States following their introduction and predicted the future distributions of both species in response to accelerating urbanization, connectivity and climate change.
Abstract: The global population at risk from mosquito-borne diseases-including dengue, yellow fever, chikungunya and Zika-is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.

605 citations



Journal ArticleDOI
TL;DR: A systematic literature search was conducted in PubMed Cochrane Library and CABI databases to evaluate the effect of breastfeeding on longterm (breast carcinoma ovarian carcinoma osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea post-partum depression postpartum weight change) maternal health outcomes.
Abstract: Aim: To evaluate the effect of breastfeeding on long-term (breast carcinoma ovarian carcinoma osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea postpartum depression postpartum weight change) maternal health outcomes. Methods: A systematic literature search was conducted in PubMed Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity subgroup analysis and meta-regression were explored. Results: Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37% respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. Conclusion: This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident. ©2015 The Authors. Open Access.

605 citations


Journal ArticleDOI
TL;DR: A review of epidemiological literature in PubMed from January 2004 to December 2013 illustrated the need for a greater attention to identifying and minimizing the effect of multicollinearity in analysis of data from epidemiologic studies.
Abstract: The adverse impact of ignoring multicollinearity on findings and data interpretation in regression analysis is very well documented in the statistical literature. The failure to identify and report multicollinearity could result in misleading interpretations of the results. A review of epidemiological literature in PubMed from January 2004 to December 2013, illustrated the need for a greater attention to identifying and minimizing the effect of multicollinearity in analysis of data from epidemiologic studies. We used simulated datasets and real life data from the Cameron County Hispanic Cohort to demonstrate the adverse effects of multicollinearity in the regression analysis and encourage researchers to consider the diagnostic for multicollinearity as one of the steps in regression analysis.

605 citations


Journal ArticleDOI
TL;DR: DGIdb v3.0 has received a major overhaul of its codebase, including an updated user interface, preset interaction search filters, consolidation of interaction information into interaction groups, greatly improved search response times and upgrading the underlying web application framework.
Abstract: The drug-gene interaction database (DGIdb, www.dgidb.org) consolidates, organizes and presents drug-gene interactions and gene druggability information from papers, databases and web resources. DGIdb normalizes content from 30 disparate sources and allows for user-friendly advanced browsing, searching and filtering for ease of access through an intuitive web user interface, application programming interface (API) and public cloud-based server image. DGIdb v3.0 represents a major update of the database. Nine of the previously included 24 sources were updated. Six new resources were added, bringing the total number of sources to 30. These updates and additions of sources have cumulatively resulted in 56 309 interaction claims. This has also substantially expanded the comprehensive catalogue of druggable genes and anti-neoplastic drug-gene interactions included in the DGIdb. Along with these content updates, v3.0 has received a major overhaul of its codebase, including an updated user interface, preset interaction search filters, consolidation of interaction information into interaction groups, greatly improved search response times and upgrading the underlying web application framework. In addition, the expanded API features new endpoints which allow users to extract more detailed information about queried drugs, genes and drug-gene interactions, including listings of PubMed IDs, interaction type and other interaction metadata.

605 citations


Journal ArticleDOI
17 Sep 2015-Nature
TL;DR: The results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain.
Abstract: The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformation of the Dirac cone often reveals intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. Dirac cones and exceptional points are connected: it was theoretically suggested that certain non-Hermitian perturbations can deform a Dirac cone and spawn a ring of exceptional points. Here we experimentally demonstrate such an 'exceptional ring' in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone resulting from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain.

605 citations


Journal ArticleDOI
TL;DR: Five C to T (or G to A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing 2.5-fold are reported.
Abstract: Base editing induces single-nucleotide changes in the DNA of living cells using a fusion protein containing a catalytically defective Streptococcus pyogenes Cas9, a cytidine deaminase, and an inhibitor of base excision repair. This genome editing approach has the advantage that it does not require formation of double-stranded DNA breaks or provision of a donor DNA template. Here we report the development of five C to T (or G to A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing 2.5-fold. Additionally, we engineered base editors containing mutated cytidine deaminase domains that narrow the width of the editing window from ∼5 nucleotides to as little as 1-2 nucleotides. We thereby enabled discrimination of neighboring C nucleotides, which would otherwise be edited with similar efficiency, and doubled the number of disease-associated target Cs able to be corrected preferentially over nearby non-target Cs.

605 citations


Journal ArticleDOI
TL;DR: The evidence is summarized and it is recommended that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability.
Abstract: Disability is an emerging field within public health; people with significant disabilities account for more than 12% of the US population. Disparity status for this group would allow federal and state governments to actively work to reduce inequities. We summarize the evidence and recommend that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability. We recommend future research and policy directions to address health inequities for individuals with disabilities; these include improved access to health care and human services, increased data to support decision-making, strengthened health and human services workforce capacity, explicit inclusion of disability in public health programs, and increased emergency preparedness.

605 citations


Journal ArticleDOI
TL;DR: Evidence is found that frailty in older-old and oldest-old surgical patients predicts post-operative mortality, complications, and prolonged length of stay, and frailty assessment may be a valuable tool in peri-operative assessment.
Abstract: As the population ages, increasing numbers of older adults are undergoing surgery. Frailty is prevalent in older adults and may be a better predictor of post-operative morbidity and mortality than chronological age. The aim of this review was to examine the impact of frailty on adverse outcomes in the ‘older old’ and ‘oldest old’ surgical patients. A systematic review was undertaken. Electronic databases from 2010 to 2015 were searched to identify articles which evaluated the relationship between frailty and post-operative outcomes in surgical populations with a mean age of 75 and older. Articles were excluded if they were in non-English languages or if frailty was measured using a single marker only. Demographic data, type of surgery performed, frailty measure and impact of frailty on adverse outcomes were extracted from the selected studies. Quality of the studies and risk of bias was assessed by the Epidemiological Appraisal Instrument. Twenty-three studies were selected for the review and they were assessed as medium to high quality. The mean age ranged from 75 to 87 years, and included patients undergoing cardiac, oncological, general, vascular and hip fracture surgeries. There were 21 different instruments used to measure frailty. Regardless of how frailty was measured, the strongest evidence in terms of numbers of studies, consistency of results and study quality was for associations between frailty and increased mortality at 30 days, 90 days and one year follow-up, post-operative complications and length of stay. A small number of studies reported on discharge to institutional care, functional decline and lower quality of life after surgery, and also found a significant association with frailty. There was strong evidence that frailty in older-old and oldest-old surgical patients predicts post-operative mortality, complications, and prolonged length of stay. Frailty assessment may be a valuable tool in peri-operative assessment. It is possible that different frailty tools are best suited for different acuity and type of surgical patients. The association between frailty and return to pre-morbid function, discharge destination, and quality of life after surgery warrants further research.

605 citations


Journal ArticleDOI
TL;DR: Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults and increasing age reduces and training experience increases the efficacy of protein supplementation during RET.
Abstract: Objective We performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength. Data sources A systematic search of Medline, Embase, CINAHL and SportDiscus. Eligibility criteria Only randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation. Design Random-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM). Results Data from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p 2 (51, 570)) and mid-femur CSA (7.2 mm 2 (0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (−0.01 kg (−0.02,–0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM. Summary/conclusion Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.

Journal ArticleDOI
TL;DR: The role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells.
Abstract: The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Furthermore, we discuss the local tissue macrophage and tumor-type specificities and their potential impact on CSF1/CSF1R-targeting treatment strategies for the future.

Journal ArticleDOI
02 Feb 2016-JAMA
TL;DR: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometAsone alone reduced endoscopic nasal polyp burden after 16 weeks.
Abstract: Importance Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell–mediated diseases. Objective To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. Design, Setting, and Participants A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. Interventions Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. Main Outcomes and Measures Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. Results Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was −0.3 (95% CI, −1.0 to 0.4) with placebo and −1.9 (95% CI, −2.5 to −1.2) with dupilumab (LS mean difference, −1.6 [95% CI, −2.4 to −0.7]; P P P P Conclusions and Relevance Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications. Trial Registration clinicaltrials.gov Identifier:NCT01920893

Journal ArticleDOI
TL;DR: Cognitive load theory was introduced in the 1980s as an instructional design theory based on several uncontroversial aspects of human cognitive architecture as discussed by the authors, which had a limited impact on the field of instructional design with most instructional design recommendations proceeding as though working memory and long-term memory did not exist.
Abstract: Cognitive load theory was introduced in the 1980s as an instructional design theory based on several uncontroversial aspects of human cognitive architecture. Our knowledge of many of the characteristics of working memory, long-term memory and the relations between them had been well-established for many decades prior to the introduction of the theory. Curiously, this knowledge had had a limited impact on the field of instructional design with most instructional design recommendations proceeding as though working memory and long-term memory did not exist. In contrast, cognitive load theory emphasised that all novel information first is processed by a capacity and duration limited working memory and then stored in an unlimited long-term memory for later use. Once information is stored in long-term memory, the capacity and duration limits of working memory disappear transforming our ability to function. By the late 1990s, sufficient data had been collected using the theory to warrant an extended analysis resulting in the publication of Sweller et al. (Educational Psychology Review, 10, 251–296, 1998). Extensive further theoretical and empirical work have been carried out since that time and this paper is an attempt to summarise the last 20 years of cognitive load theory and to sketch directions for future research.

Proceedings ArticleDOI
07 Jun 2015
TL;DR: This work proposes an effective deep learning framework to generate binary hash codes for fast image retrieval by employing a hidden layer for representing the latent concepts that dominate the class labels in convolutional neural networks.
Abstract: Approximate nearest neighbor search is an efficient strategy for large-scale image retrieval. Encouraged by the recent advances in convolutional neural networks (CNNs), we propose an effective deep learning framework to generate binary hash codes for fast image retrieval. Our idea is that when the data labels are available, binary codes can be learned by employing a hidden layer for representing the latent concepts that dominate the class labels. The utilization of the CNN also allows for learning image representations. Unlike other supervised methods that require pair-wised inputs for binary code learning, our method learns hash codes and image representations in a point-wised manner, making it suitable for large-scale datasets. Experimental results show that our method outperforms several state-of-the-art hashing algorithms on the CIFAR-10 and MNIST datasets. We further demonstrate its scalability and efficacy on a large-scale dataset of 1 million clothing images.

Journal ArticleDOI
TL;DR: Results indicate that cir-ITCH may have an inhibitory effect on ESCC by regulating the Wnt pathway.
Abstract: // Fang Li 1,* , Liyuan Zhang 2,* , Wei Li 1 , Jieqiong Deng 1 , Jian Zheng 1 , Mingxing An 1 , Jiachun Lu 3 and Yifeng Zhou 1 1 Department of Genetics, Medical College of Soochow University, Suzhou, China 2 Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China 3 The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Yifeng Zhou, email: // Keywords : Cir-ITCH, ESCC, Wnt/β-catenin pathway Received : December 01, 2014 Accepted : January 20, 2015 Published : February 28, 2015 Abstract Circular RNAs with exonic sequences represent a special form of non-coding RNAs, discovered by analyzing a handful of transcribed genes. It has been observed that circular RNAs function as microRNA sponges. In the present study, we investigated whether the expression of circular RNAs is altered during the development of esophageal squamous cell carcinoma (ESCC). Using a TaqMan-based reverse transcriptase polymerase chain reaction assay, the relationship between cir-ITCH and ESCC was analyzed in a total of 684 ESCC and paired adjacent non-tumor tissue samples from eastern and southern China. We found that cir-ITCH expression was usually low in ESCC compared to the peritumoral tissue. The functional relevance of cir-ITCH was further examined by biochemical assays. As sponge of miR-7, miR-17, and miR-214, cir-ITCH might increase the level of ITCH . ITCH hyper expression promotes ubiquitination and degradation of phosphorylated Dvl2, thereby inhibiting the Wnt/β-catenin pathway. These results indicate that cir-ITCH may have an inhibitory effect on ESCC by regulating the Wnt pathway.

Journal ArticleDOI
TL;DR: NAFLD is becoming a major cause of HCC in the United States and is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT.

Journal ArticleDOI
28 Mar 2016-RNA
TL;DR: For future RNA-seq experiments, results suggest that at least six biological replicates should be used, rising to at least 12 when it is important to identify SDE genes for all fold changes, and if fewer than 12 replicates are used, a superior combination of true positive and false positive performances makes edgeR and DESeq2 the leading tools.
Abstract: RNA-seq is now the technology of choice for genome-wide differential gene expression experiments, but it is not clear how many biological replicates are needed to ensure valid biological interpretation of the results or which statistical tools are best for analyzing the data. An RNA-seq experiment with 48 biological replicates in each of two conditions was performed to answer these questions and provide guidelines for experimental design. With three biological replicates, nine of the 11 tools evaluated found only 20%–40% of the significantly differentially expressed (SDE) genes identified with the full set of 42 clean replicates. This rises to >85% for the subset of SDE genes changing in expression by more than fourfold. To achieve >85% for all SDE genes regardless of fold change requires more than 20 biological replicates. The same nine tools successfully control their false discovery rate at ≲5% for all numbers of replicates, while the remaining two tools fail to control their FDR adequately, particularly for low numbers of replicates. For future RNA-seq experiments, these results suggest that at least six biological replicates should be used, rising to at least 12 when it is important to identify SDE genes for all fold changes. If fewer than 12 replicates are used, a superior combination of true positive and false positive performances makes edgeR and DESeq2 the leading tools. For higher replicate numbers, minimizing false positives is more important and DESeq marginally outperforms the other tools.

Journal ArticleDOI
TL;DR: It is shown that online MBIs have potential to contribute to improving mental health outcomes, particularly stress, and that effect sizes for stress were significantly moderated by the number of intervention sessions.

Journal ArticleDOI
09 Aug 2016-JAMA
TL;DR: Among US adults with diabetes from 1988 to 2014, the overall prevalence of diabetic kidney disease did not change significantly, whereas the prevalence of albuminuria declined and thePrevalence of reduced eGFR increased.
Abstract: Importance Diabetic kidney disease is the leading cause of chronic and end-stage kidney disease in the United States and worldwide. Changes in demographics and treatments may affect the prevalence and clinical manifestations of diabetic kidney disease. Objective To characterize the clinical manifestations of kidney disease among US adults with diabetes over time. Design, Setting, and Participants Serial cross-sectional studies of adults aged 20 years or older with diabetes mellitus participating in National Health and Nutrition Examination Surveys from 1988 through 2014. Exposures Diabetes was defined as hemoglobin A 1c greater than 6.5% or use of glucose-lowering medications. Main Outcomes and Measures Albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), macroalbuminuria (urine albumin-to-creatinine ratio ≥300 mg/g), reduced estimated glomerular filtration rate (eGFR 2 ), and severely reduced eGFR ( 2 ), incorporating data on biological variability to estimate the prevalence of persistent abnormalities. Results There were 6251 adults with diabetes included (1431 from 1988-1994, 1443 from 1999-2004, 1280 from 2005-2008, and 2097 from 2009-2014). The prevalence of any diabetic kidney disease, defined as persistent albuminuria, persistent reduced eGFR, or both, did not significantly change over time from 28.4% (95% CI, 23.8%-32.9%) in 1988-1994 to 26.2% (95% CI, 22.6%-29.9%) in 2009-2014 (prevalence ratio, 0.95 [95% CI, 0.86-1.06] adjusting for age, sex, and race/ethnicity; P = .39 for trend). However, the prevalence of albuminuria decreased progressively over time from 20.8% (95% CI, 16.3%-25.3%) in 1988-1994 to 15.9% (95% CI, 12.7%-19.0%) in 2009-2014 (adjusted prevalence ratio, 0.76 [95% CI, 0.65-0.89]; P P P = .004 for trend). Significant heterogeneity in the temporal trend for albuminuria was noted by age ( P = .049 for interaction) and race/ethnicity ( P = .007 for interaction), with a decreasing prevalence of albuminuria observed only among adults younger than 65 years and non-Hispanic whites, whereas the prevalence of reduced GFR increased without significant differences by age or race/ethnicity. In 2009-2014, approximately 8.2 million adults with diabetes (95% CI, 6.5-9.9 million adults) had albuminuria, reduced eGFR, or both. Conclusions and Relevance Among US adults with diabetes from 1988 to 2014, the overall prevalence of diabetic kidney disease did not change significantly, whereas the prevalence of albuminuria declined and the prevalence of reduced eGFR increased.

Proceedings Article
30 Apr 2020
TL;DR: Dreamer is presented, a reinforcement learning agent that solves long-horizon tasks purely by latent imagination and efficiently learn behaviors by backpropagating analytic gradients of learned state values through trajectories imagined in the compact state space of a learned world model.
Abstract: To select effective actions in complex environments, intelligent agents need to generalize from past experience. World models can represent knowledge about the environment to facilitate such generalization. While learning world models from high-dimensional sensory inputs is becoming feasible through deep learning, there are many potential ways for deriving behaviors from them. We present Dreamer, a reinforcement learning agent that solves long-horizon tasks purely by latent imagination. We efficiently learn behaviors by backpropagating analytic gradients of learned state values through trajectories imagined in the compact state space of a learned world model. On 20 challenging visual control tasks, Dreamer exceeds existing approaches in data-efficiency, computation time, and final performance.

Journal ArticleDOI
TL;DR: Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.
Abstract: PurposeThis multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen.Patients and MethodsPatients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control—progression-free survival (PFS), time to progression, objective response rate, and duration of response—as well as safety and patient-reported symptom scoring.ResultsA total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); b...

Journal ArticleDOI
TL;DR: The PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist as discussed by the authors was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process.
Abstract: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process. The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale. The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.

Journal ArticleDOI
15 Feb 2015-Cancer
TL;DR: This study sought to examine the epidemiologic characteristics of NETs and the contribution of early‐stage detection to the rising incidence and patterns of metastatic presentation.
Abstract: BACKGROUND An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence METHODS A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS) RESULTS Five thousand six hundred nineteen NET cases were identified The incidence of NETs increased from 248 to 586 per 100,000 per year Metastases were found in 208% at presentation and in another 38% after the initial diagnosis The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%) Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (063-069 per 100,000 per year) The 10-year OS rate was 465%, and the RFS rate was 646% In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P < 0001), male sex (P < 0001), a low socioeconomic status (P < 0001), and rural living (P = 0049) CONCLUSIONS The incidence of NETs has markedly increased over the course of 15 years This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs Cancer 2015;121:589–597 © 2014 American Cancer Society

Journal ArticleDOI
TL;DR: One of the two main configurations can be chosen when designing an integrated first- and second-generation ethanol production plant from grain and straw: that producing biogas or that producing distiller’s dried grains with solubles from the xylose sugars, since the prices for both co-products have fluctuated a great deal in recent years.
Abstract: Integration of first- and second-generation ethanol production can facilitate the introduction of second-generation lignocellulosic ethanol production. Consolidation of the second-generation with the first-generation process can potentially reduce the downstream processing cost for the second-generation process as well as providing the first-generation process with energy. This study presents novel experimental results from integrated first- and second-generation ethanol production from grain and wheat straw in a process development unit. The results were used in techno-economic evaluations to investigate the feasibility of the plant, in which the main co-products were distiller’s dried grains with solubles and biogas. An overall glucose to ethanol yield, of 81 % of the theoretical, based on glucose available in the raw material, was achieved in the experiments. A positive net present value was found for all the base case scenarios and the minimal ethanol selling price varied between 0.45 and 0.53 EUR/L ethanol. The revenue increased with combined xylose and glucose fermentation and biogas upgrading to vehicle fuel quality. A decrease in the biogas yield from 80 to 60 % also largely affects the net present value. The energy efficiency for the energy content in products available for sale compared with the incoming energy content varied from 74 to 80 %. One of the two main configurations can be chosen when designing an integrated first- and second-generation ethanol production plant from grain and straw: that producing biogas or that producing distiller’s dried grains with solubles from the xylose sugars. The choice depends mainly on the local market and prices for distiller’s dried grains with solubles and biogas, since the prices for both co-products have fluctuated a great deal in recent years. In the current study, however, distiller’s dried grains with solubles were found to be a more promising co-product than biogas, if the biogas was not upgraded to vehicle fuel quality. It was also concluded that additional experimental data from biogas production using first- and second-generation substrates are required to obtain improved economic evaluations.

Journal ArticleDOI
TL;DR: In this article, the responses of seropositive persons to a single SARS-CoV-2 vaccine were surveyed and they reported that they had antibodies to the spike protein of SARS CoV2.
Abstract: Responses of Seropositive Persons to a Single SARS-CoV-2 Vaccine Some persons who have recovered from Covid-19 have antibodies to the spike protein of SARS-CoV-2. In 43 such persons who had receive...

Journal ArticleDOI
TL;DR: In this article, the photocatalytic degradation of dyes in aqueous solution using TiO2 as photocatalyst under solar and UV irradiation has been reviewed.
Abstract: Traditional chemical, physical and biological processes for treating wastewater containing textile dye have such disadvantages as high cost, high energy requirement and generation of secondary pollution during treatment process. The advanced oxidation processes technology has been attracting growing attention for the decomposition of organic dyes. Such processes are based on the light-enhanced generation of highly reactive hydroxyl radicals, which oxidize the organic matter in solution and convert it completely into water, CO2 and inorganic compounds. In this presentation, the photocatalytic degradation of dyes in aqueous solution using TiO2 as photocatalyst under solar and UV irradiation has been reviewed. It is observed that the degradation of dyes depends on several parameters such as pH, catalyst concentration, substrate concentration and the presence of oxidants. Reaction temperature and the intensity of light also affect the degradation of dyes. Particle size, BET-surface area and different mineral forms of TiO2 also have influence on the degradation rate.

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TL;DR: The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID‐19 during pregnancy.
Abstract: Introduction The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. Material and methods We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. Results Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. Conclusions Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

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TL;DR: Transient optoelectronic measurements combined with device simulations indicate that electric-field screening, consistent with ion migration, is similar in both high and low hysteresis CH3NH3PbI3 cells.
Abstract: Ion migration has been proposed as a possible cause of photovoltaic current–voltage hysteresis in hybrid perovskite solar cells. A major objection to this hypothesis is that hysteresis can be reduced by changing the interfacial contact materials; however, this is unlikely to significantly influence the behaviour of mobile ionic charge within the perovskite phase. Here, we show that the primary effects of ion migration can be observed regardless of whether the contacts were changed to give devices with or without significant hysteresis. Transient optoelectronic measurements combined with device simulations indicate that electric-field screening, consistent with ion migration, is similar in both high and low hysteresis CH3NH3PbI3 cells. Simulation of the photovoltage and photocurrent transients shows that hysteresis requires the combination of both mobile ionic charge and recombination near the perovskite-contact interfaces. Passivating contact recombination results in higher photogenerated charge concentrations at forward bias which screen the ionic charge, reducing hysteresis. Ion migration has been related to hysteresis in perovskite solar cells, but not all perovskite cells exhibit a hysteresis. Here, Caladoet al. show that ion migration occurs regardless of hysteresis, but photogenerated carriers screen the effects of ionic charge for some solar cell architectures.

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TL;DR: The question that arises now is, how to develop a high performance platform to efficiently analyze big data and how to design an appropriate mining algorithm to find the useful things from big data.
Abstract: The age of big data is now coming. But the traditional data analytics may not be able to handle such large quantities of data. The question that arises now is, how to develop a high performance platform to efficiently analyze big data and how to design an appropriate mining algorithm to find the useful things from big data. To deeply discuss this issue, this paper begins with a brief introduction to data analytics, followed by the discussions of big data analytics. Some important open issues and further research directions will also be presented for the next step of big data analytics.