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Journal ArticleDOI
27 Apr 2018-Science
TL;DR: ShERLOCK as discussed by the authors is a platform that combines isothermal preamplification with Cas13 to detect single molecules of RNA or DNA, which can detect Dengue or Zika virus single-stranded RNA and mutations in patient liquid biopsy samples via lateral flow.
Abstract: Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) that combines isothermal preamplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCK version 2 (SHERLOCKv2) (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout. SHERLOCKv2 can detect Dengue or Zika virus single-stranded RNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.

1,356 citations


Book
01 Jan 2017
TL;DR: In this article, the authors provide six styles of leadership: coercive leaders, authoritative leaders, affiliative leaders, democratic leaders, pacesetting leaders, and coaching leaders, based on self-awareness, selfmanagement, social awareness, and social skill.
Abstract: Emotional Intelligence-the ability to manage one and their relationships effectively-consists of four fundamental capabilities self-awareness, self-management, social awareness, and social skill. This chapter provides six styles of leadership. They are coercive leaders, authoritative leaders, affiliative leaders, democratic leaders, pacesetting leaders, and coaching leaders. Coercive leadership has a damaging effect on the rewards system. Most high-performing workers are motivated by more than money–they seek the satisfaction of work well done. The coercive style erodes such pride. Authoritative leadership maximizes commitment to the organization's goals and strategy. By framing the individual tasks within a grand vision, the authoritative leader defines standards that revolve around that vision. Affiliative leaders are masters at building a sense of belonging. They are, for instance, likely to take their direct reports out for a meal or a drink, one-on-one, to see how they're doing. They will bring in a cake to celebrate a group accomplishment.

1,356 citations


Posted Content
TL;DR: This short book reviews OT with a bias toward numerical methods and their applications in data sciences, and sheds lights on the theoretical properties of OT that make it particularly useful for some of these applications.
Abstract: Optimal transport (OT) theory can be informally described using the words of the French mathematician Gaspard Monge (1746-1818): A worker with a shovel in hand has to move a large pile of sand lying on a construction site. The goal of the worker is to erect with all that sand a target pile with a prescribed shape (for example, that of a giant sand castle). Naturally, the worker wishes to minimize her total effort, quantified for instance as the total distance or time spent carrying shovelfuls of sand. Mathematicians interested in OT cast that problem as that of comparing two probability distributions, two different piles of sand of the same volume. They consider all of the many possible ways to morph, transport or reshape the first pile into the second, and associate a "global" cost to every such transport, using the "local" consideration of how much it costs to move a grain of sand from one place to another. Recent years have witnessed the spread of OT in several fields, thanks to the emergence of approximate solvers that can scale to sizes and dimensions that are relevant to data sciences. Thanks to this newfound scalability, OT is being increasingly used to unlock various problems in imaging sciences (such as color or texture processing), computer vision and graphics (for shape manipulation) or machine learning (for regression, classification and density fitting). This short book reviews OT with a bias toward numerical methods and their applications in data sciences, and sheds lights on the theoretical properties of OT that make it particularly useful for some of these applications.

1,355 citations


Journal ArticleDOI
TL;DR: These data show that lumacaftor in combination with ivacaftors provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation.
Abstract: A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV 1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor–ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV 1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor–ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor–ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor–ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor–ivacaftor versus 1.6% among those who received placebo. CONCLUSIONS These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.)

1,355 citations


Proceedings Article
12 Jul 2020
TL;DR: SimCLR as mentioned in this paper is a simple framework for contrastive learning of visual representations and achieves state-of-the-art performance on ImageNet. But it requires large batch sizes and more training steps compared to supervised learning.
Abstract: This paper presents SimCLR: a simple framework for contrastive learning of visual representations. We simplify recently proposed contrastive self-supervised learning algorithms without requiring specialized architectures or a memory bank. In order to understand what enables the contrastive prediction tasks to learn useful representations, we systematically study the major components of our framework. We show that (1) composition of data augmentations plays a critical role in defining effective predictive tasks, (2) introducing a learnable nonlinear transformation between the representation and the contrastive loss substantially improves the quality of the learned representations, and (3) contrastive learning benefits from larger batch sizes and more training steps compared to supervised learning. By combining these findings, we are able to considerably outperform previous methods for self-supervised and semi-supervised learning on ImageNet. A linear classifier trained on self-supervised representations learned by SimCLR achieves 76.5% top-1 accuracy, which is a 7% relative improvement over previous state-of-the-art, matching the performance of a supervised ResNet-50. When fine-tuned on only 1% of the labels, we achieve 85.8% top-5 accuracy, outperforming AlexNet with 100X fewer labels.

1,355 citations


Journal ArticleDOI
TL;DR: The results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells and provide strong support for further development of this approach.
Abstract: Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19 B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/L.

1,354 citations


Journal ArticleDOI
TL;DR: Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer.
Abstract: Background Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131). Methods In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety. Results The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related. Conclusions Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131– refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.)

1,354 citations


Journal ArticleDOI
Andrew I R Maas1, David K. Menon2, P. David Adelson3, Nada Andelic4  +339 moreInstitutions (110)
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators

1,354 citations


Journal ArticleDOI
TL;DR: The case burden of TBI across World Health Organization regions and World Bank income groups was sought to promote advocacy, understanding, and targeted intervention, and study quality was higher in the high-income countries (HICs) than in the low- and middle- Income countries (LMICs).
Abstract: OBJECTIVETraumatic brain injury (TBI)—the “silent epidemic”—contributes to worldwide death and disability more than any other traumatic insult. Yet, TBI incidence and distribution across regions and socioeconomic divides remain unknown. In an effort to promote advocacy, understanding, and targeted intervention, the authors sought to quantify the case burden of TBI across World Health Organization (WHO) regions and World Bank (WB) income groups.METHODSOpen-source epidemiological data on road traffic injuries (RTIs) were used to model the incidence of TBI using literature-derived ratios. First, a systematic review on the proportion of RTIs resulting in TBI was conducted, and a meta-analysis of study-derived proportions was performed. Next, a separate systematic review identified primary source studies describing mechanisms of injury contributing to TBI, and an additional meta-analysis yielded a proportion of TBI that is secondary to the mechanism of RTI. Then, the incidence of RTI as published by the Global...

1,353 citations


Book
03 Jan 2018
TL;DR: This monograph summarizes many years of research insights in a clear and self-contained way and providest the reader with the necessary knowledge and mathematical toolsto carry out independent research in this area.
Abstract: Massive multiple-input multiple-output MIMO is one of themost promising technologies for the next generation of wirelesscommunication networks because it has the potential to providegame-changing improvements in spectral efficiency SE and energyefficiency EE. This monograph summarizes many years ofresearch insights in a clear and self-contained way and providesthe reader with the necessary knowledge and mathematical toolsto carry out independent research in this area. Starting froma rigorous definition of Massive MIMO, the monograph coversthe important aspects of channel estimation, SE, EE, hardwareefficiency HE, and various practical deployment considerations.From the beginning, a very general, yet tractable, canonical systemmodel with spatial channel correlation is introduced. This modelis used to realistically assess the SE and EE, and is later extendedto also include the impact of hardware impairments. Owing tothis rigorous modeling approach, a lot of classic "wisdom" aboutMassive MIMO, based on too simplistic system models, is shownto be questionable.

1,352 citations


Journal ArticleDOI
18 May 2018-Science
TL;DR: A copper electrocatalyst at an abrupt reaction interface in an alkaline electrolyte reduces CO2 to ethylene with 70% faradaic efficiency at a potential of −0.55 volts versus a reversible hydrogen electrode (RHE).
Abstract: Carbon dioxide (CO 2 ) electroreduction could provide a useful source of ethylene, but low conversion efficiency, low production rates, and low catalyst stability limit current systems. Here we report that a copper electrocatalyst at an abrupt reaction interface in an alkaline electrolyte reduces CO 2 to ethylene with 70% faradaic efficiency at a potential of −0.55 volts versus a reversible hydrogen electrode (RHE). Hydroxide ions on or near the copper surface lower the CO 2 reduction and carbon monoxide (CO)–CO coupling activation energy barriers; as a result, onset of ethylene evolution at −0.165 volts versus an RHE in 10 molar potassium hydroxide occurs almost simultaneously with CO production. Operational stability was enhanced via the introduction of a polymer-based gas diffusion layer that sandwiches the reaction interface between separate hydrophobic and conductive supports, providing constant ethylene selectivity for an initial 150 operating hours.

ReportDOI
03 Jun 2015
TL;DR: This document provides guidance on how to secure Industrial Control Systems, including Supervisory Control and Data Acquisition systems, Distributed Control Systems (DCS), and other control system configurations such as Programmable Logic Controllers (PLC), while addressing their unique performance, reliability, and safety requirements.
Abstract: This document provides guidance on how to secure Industrial Control Systems (ICS), including Supervisory Control and Data Acquisition (SCADA) systems, Distributed Control Systems (DCS), and other control system configurations such as Programmable Logic Controllers (PLC), while addressing their unique performance, reliability, and safety requirements The document provides an overview of ICS and typical system topologies, identifies typical threats and vulnerabilities to these systems, and provides recommended security countermeasures to mitigate the associated risks


Journal ArticleDOI
06 Dec 2016-JAMA
TL;DR: A systematic review of studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016 found that strategies for preventing and treating these disorders in this population of medical students are needed.
Abstract: Importance Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies. Objective To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students. Data Sources and Study Selection Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included. Data Extraction and Synthesis Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Main Outcomes and Measures Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview. Results Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I2 = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015; slope, 0.2% increase per year [95% CI, −0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I2 = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I2 = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%. Conclusions and Relevance In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.

Journal ArticleDOI
TL;DR: This paper analyzes the MEC reference architecture and main deployment scenarios, which offer multi-tenancy support for application developers, content providers, and third parties, and elaborates further on open research challenges.
Abstract: Multi-access edge computing (MEC) is an emerging ecosystem, which aims at converging telecommunication and IT services, providing a cloud computing platform at the edge of the radio access network MEC offers storage and computational resources at the edge, reducing latency for mobile end users and utilizing more efficiently the mobile backhaul and core networks This paper introduces a survey on MEC and focuses on the fundamental key enabling technologies It elaborates MEC orchestration considering both individual services and a network of MEC platforms supporting mobility, bringing light into the different orchestration deployment options In addition, this paper analyzes the MEC reference architecture and main deployment scenarios, which offer multi-tenancy support for application developers, content providers, and third parties Finally, this paper overviews the current standardization activities and elaborates further on open research challenges

Journal ArticleDOI
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Abstract: Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (l...

Journal ArticleDOI
TL;DR: The core CSF biomarkers of neurodegeneration (T-tau, P-tAU, and Aβ42), CSF NFL, and plasma T-t Tau were strongly associated with Alzheimer's disease and the core biomarkers were strong associated with mild cognitive impairment due to Alzheimer's Disease.
Abstract: Summary Background Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. Methods In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood–brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline. Findings Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44–2·64, p Interpretation The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma Aβ42 and Aβ40 were not. Due to their consistency, T-tau, P-tau, Aβ42, and NFL in CSF should be used in clinical practice and clinical research. Funding Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Soderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.

Journal ArticleDOI
12 Jul 2018-BMJ
TL;DR: In this article, the authors provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from such studies in the context of other sources of evidence.
Abstract: Mendelian randomisation uses genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data. As with all epidemiological approaches, findings from Mendelian randomisation studies depend on specific assumptions. We provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from Mendelian randomisation studies in the context of other sources of evidence

Journal ArticleDOI
TL;DR: This paper seeks to raise awareness of information bias in observational and experimental research study designs as well as to enrich discussions concerning bias problems to improve clinical evaluation and health care practice.
Abstract: As with other fields, medical sciences are subject to different sources of bias. While understanding sources of bias is a key element for drawing valid conclusions, bias in health research continues to be a very sensitive issue that can affect the focus and outcome of investigations. Information bias, otherwise known as misclassification, is one of the most common sources of bias that affects the validity of health research. It originates from the approach that is utilized to obtain or confirm study measurements. This paper seeks to raise awareness of information bias in observational and experimental research study designs as well as to enrich discussions concerning bias problems. Specifying the types of bias can be essential to limit its effects and, the use of adjustment methods might serve to improve clinical evaluation and health care practice.

Journal ArticleDOI
26 Jul 2016-eLife
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

Journal ArticleDOI
TL;DR: Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission, and black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients.
Abstract: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

Journal ArticleDOI
21 Jan 2015-Neuron
TL;DR: The data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment.

Journal ArticleDOI
01 Sep 2020
TL;DR: There is a high burden of depression symptoms in the US associated with the COVID-19 pandemic and that this burden falls disproportionately on individuals who are already at increased risk.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic and the policies to contain it have been a near ubiquitous exposure in the US with unknown effects on depression symptoms. Objective To estimate the prevalence of and risk factors associated with depression symptoms among US adults during vs before the COVID-19 pandemic. Design, Setting, and Participants This nationally representative survey study used 2 population-based surveys of US adults aged 18 or older. During COVID-19, estimates were derived from the COVID-19 and Life Stressors Impact on Mental Health and Well-being study, conducted from March 31, 2020, to April 13, 2020. Before COVID-19 estimates were derived from the National Health and Nutrition Examination Survey, conducted from 2017 to 2018. Data were analyzed from April 15 to 20, 2020. Exposures The COVID-19 pandemic and outcomes associated with the measures to mitigate it. Main Outcomes and Measures Depression symptoms, defined using the Patient Health Questionnaire-9 cutoff of 10 or higher. Categories of depression symptoms were defined as none (score, 0-4), mild (score, 5-9), moderate (score, 10-14), moderately severe (score, 15-19), and severe (score, ≥20). Results A total of 1470 participants completed the COVID-19 and Life Stressors Impact on Mental Health and Well-being survey (completion rate, 64.3%), and after removing those with missing data, the final during–COVID-19 sample included 1441 participants (619 participants [43.0%] aged 18-39 years; 723 [50.2%] men; 933 [64.7%] non-Hispanic White). The pre–COVID-19 sample included 5065 participants (1704 participants [37.8%] aged 18-39 years; 2588 [51.4%] women; 1790 [62.9%] non-Hispanic White). Depression symptom prevalence was higher in every category during COVID-19 compared with before (mild: 24.6% [95% CI, 21.8%-27.7%] vs 16.2% [95% CI, 15.1%-17.4%]; moderate: 14.8% [95% CI, 12.6%-17.4%] vs 5.7% [95% CI, 4.8%-6.9%]; moderately severe: 7.9% [95% CI, 6.3%-9.8%] vs 2.1% [95% CI, 1.6%-2.8%]; severe: 5.1% [95% CI, 3.8%-6.9%] vs 0.7% [95% CI, 0.5%-0.9%]). Higher risk of depression symptoms during COVID-19 was associated with having lower income (odds ratio, 2.37 [95% CI, 1.26-4.43]), having less than $5000 in savings (odds ratio, 1.52 [95% CI, 1.02-2.26]), and exposure to more stressors (odds ratio, 3.05 [95% CI, 1.95-4.77]). Conclusions and Relevance These findings suggest that prevalence of depression symptoms in the US was more than 3-fold higher during COVID-19 compared with before the COVID-19 pandemic. Individuals with lower social resources, lower economic resources, and greater exposure to stressors (eg, job loss) reported a greater burden of depression symptoms. Post–COVID-19 plans should account for the probable increase in mental illness to come, particularly among at-risk populations.

Journal ArticleDOI
TL;DR: In three online studies, participants from MTurk and collegiate populations participated in a task that included a measure of attentiveness to instructions (an instructional manipulation check: IMC), and MTurkers were more attentive to the instructions than were college students, even on novel IMCs.
Abstract: Participant attentiveness is a concern for many researchers using Amazon’s Mechanical Turk (MTurk). Although studies comparing the attentiveness of participants on MTurk versus traditional subject pool samples have provided mixed support for this concern, attention check questions and other methods of ensuring participant attention have become prolific in MTurk studies. Because MTurk is a population that learns, we hypothesized that MTurkers would be more attentive to instructions than are traditional subject pool samples. In three online studies, participants from MTurk and collegiate populations participated in a task that included a measure of attentiveness to instructions (an instructional manipulation check: IMC). In all studies, MTurkers were more attentive to the instructions than were college students, even on novel IMCs (Studies 2 and 3), and MTurkers showed larger effects in response to a minute text manipulation. These results have implications for the sustainable use of MTurk samples for social science research and for the conclusions drawn from research with MTurk and college subject pool samples.

Book ChapterDOI
Yandong Guo1, Lei Zhang1, Yuxiao Hu1, Xiaodong He1, Jianfeng Gao1 
08 Oct 2016
TL;DR: In this article, the authors proposed a benchmark task to recognize one million celebrities from their face images, by using all the possibly collected face images of this individual on the web as training data.
Abstract: In this paper, we design a benchmark task and provide the associated datasets for recognizing face images and link them to corresponding entity keys in a knowledge base. More specifically, we propose a benchmark task to recognize one million celebrities from their face images, by using all the possibly collected face images of this individual on the web as training data. The rich information provided by the knowledge base helps to conduct disambiguation and improve the recognition accuracy, and contributes to various real-world applications, such as image captioning and news video analysis. Associated with this task, we design and provide concrete measurement set, evaluation protocol, as well as training data. We also present in details our experiment setup and report promising baseline results. Our benchmark task could lead to one of the largest classification problems in computer vision. To the best of our knowledge, our training dataset, which contains 10M images in version 1, is the largest publicly available one in the world.

Journal ArticleDOI
TL;DR: Synthesized Member Checking addresses the co-constructed nature of knowledge by providing participants with the opportunity to engage with, and add to, interview and interpreted data, several months after their semi-structured interview.
Abstract: The trustworthiness of results is the bedrock of high quality qualitative research. Member checking, also known as participant or respondent validation, is a technique for exploring the credibility of results. Data or results are returned to participants to check for accuracy and resonance with their experiences. Member checking is often mentioned as one in a list of validation techniques. This simplistic reporting might not acknowledge the value of using the method, nor its juxtaposition with the interpretative stance of qualitative research. In this commentary, we critique how member checking has been used in published research, before describing and evaluating an innovative in-depth member checking technique, Synthesized Member Checking. The method was used in a study with patients diagnosed with melanoma. Synthesized Member Checking addresses the co-constructed nature of knowledge by providing participants with the opportunity to engage with, and add to, interview and interpreted data, several months after their semi-structured interview.

Journal ArticleDOI
TL;DR: An overarching organization of large-scale connectivity that situates the default-mode network at the opposite end of a spectrum from primary sensory and motor regions is described, suggesting that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.
Abstract: Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface-and are precisely equidistant-from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.

Journal ArticleDOI
TL;DR: It is demonstrated that efficient fixation of N2 to NH3 can proceed under room temperature and atmospheric pressure in water using visible light illuminated BiOBr nanosheets of oxygen vacancies in the absence of any organic scavengers and precious-metal cocatalysts.
Abstract: Even though the well-established Haber–Bosch process has been the major artificial way to “fertilize” the earth, its energy-intensive nature has been motivating people to learn from nitrogenase, which can fix atmospheric N2 to NH3 in vivo under mild conditions with its precisely arranged proteins Here we demonstrate that efficient fixation of N2 to NH3 can proceed under room temperature and atmospheric pressure in water using visible light illuminated BiOBr nanosheets of oxygen vacancies in the absence of any organic scavengers and precious-metal cocatalysts The designed catalytic oxygen vacancies of BiOBr nanosheets on the exposed {001} facets, with the availability of localized electrons for π-back-donation, have the ability to activate the adsorbed N2, which can thus be efficiently reduced to NH3 by the interfacial electrons transferred from the excited BiOBr nanosheets This study might open up a new vista to fix atmospheric N2 to NH3 through the less energy-demanding photochemical process

Posted Content
TL;DR: A family of algorithms for learning a parameter initialization that can be fine-tuned quickly on a new task, using only first-order derivatives for the meta-learning updates, including Reptile, which works by repeatedly sampling a task, training on it, and moving the initialization towards the trained weights on that task.
Abstract: This paper considers meta-learning problems, where there is a distribution of tasks, and we would like to obtain an agent that performs well (i.e., learns quickly) when presented with a previously unseen task sampled from this distribution. We analyze a family of algorithms for learning a parameter initialization that can be fine-tuned quickly on a new task, using only first-order derivatives for the meta-learning updates. This family includes and generalizes first-order MAML, an approximation to MAML obtained by ignoring second-order derivatives. It also includes Reptile, a new algorithm that we introduce here, which works by repeatedly sampling a task, training on it, and moving the initialization towards the trained weights on that task. We expand on the results from Finn et al. showing that first-order meta-learning algorithms perform well on some well-established benchmarks for few-shot classification, and we provide theoretical analysis aimed at understanding why these algorithms work.

Journal ArticleDOI
TL;DR: A new open-source release of the Maxent software for modeling species distributions from occurrence records and environmental data is announced, and a new R package for fitting Maxent models using the glmnet package for regularized generalized linear models is described.
Abstract: This software note announces a new open-source release of the Maxent software for modeling species distributions from occurrence records and environmental data, and describes a new R package for fitting such models. The new release (ver. 3.4.0) will be hosted online by the American Museum of Natural History, along with future versions. It contains small functional changes, most notably use of a complementary log-log (cloglog) transform to produce an estimate of occurrence probability. The cloglog transform derives from the recently-published interpretation of Maxent as an inhomogeneous Poisson process (IPP), giving it a stronger theoretical justification than the logistic transform which it replaces by default. In addition, the new R package, maxnet, fits Maxent models using the glmnet package for regularized generalized linear models. We discuss the implications of the IPP formulation in terms of model inputs and outputs, treating occurrence records as points rather than grid cells and interpreting the exponential Maxent model (raw output) as as an estimate of relative abundance. With these two open-source developments, we invite others to freely use and contribute to the software.