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Journal ArticleDOI
TL;DR: Although the mortality reduction was not significant in the primary analysis, it was noted a significant mortality reduction with MMS when prevalent cases were excluded, and encouraging evidence of a mortality reduction in years 7–14 was noted.

756 citations


Journal ArticleDOI
TL;DR: The high and rather selective tumor uptake on 68Ga-FAPI PET/CT may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.
Abstract: The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods:68Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122–312 MBq of 68Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUVmax and SUVmean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUVmax (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax

756 citations


Journal ArticleDOI
TL;DR: Ease-of-use improvements include helper functions to standardize model parameters and compute their Jacobian-based standard errors, access to model components through standard R $ mechanisms, and improved tab completion from within the R Graphical User Interface.
Abstract: The new software package OpenMx 2.0 for structural equation and other statistical modeling is introduced and its features are described. OpenMx is evolving in a modular direction and now allows a mix-and-match computational approach that separates model expectations from fit functions and optimizers. Major backend architectural improvements include a move to swappable open-source optimizers such as the newly written CSOLNP. Entire new methodologies such as item factor analysis and state space modeling have been implemented. New model expectation functions including support for the expression of models in LISREL syntax and a simplified multigroup expectation function are available. Ease-of-use improvements include helper functions to standardize model parameters and compute their Jacobian-based standard errors, access to model components through standard R $ mechanisms, and improved tab completion from within the R Graphical User Interface.

756 citations


Proceedings Article
04 Feb 2017
TL;DR: A novel Modularized Nonnegative Matrix Factorization (M-NMF) model is proposed to incorporate the community structure into network embedding and jointly optimize NMF based representation learning model and modularity based community detection model in a unified framework, which enables the learned representations of nodes to preserve both of the microscopic and community structures.
Abstract: Network embedding, aiming to learn the low-dimensional representations of nodes in networks, is of paramount importance in many real applications. One basic requirement of network embedding is to preserve the structure and inherent properties of the networks. While previous network embedding methods primarily preserve the microscopic structure, such as the first- and second-order proximities of nodes, the mesoscopic community structure, which is one of the most prominent feature of networks, is largely ignored. In this paper, we propose a novel Modularized Nonnegative Matrix Factorization (M-NMF) model to incorporate the community structure into network embedding. We exploit the consensus relationship between the representations of nodes and community structure, and then jointly optimize NMF based representation learning model and modularity based community detection model in a unified framework, which enables the learned representations of nodes to preserve both of the microscopic and community structures. We also provide efficient updating rules to infer the parameters of our model, together with the correctness and convergence guarantees. Extensive experimental results on a variety of real-world networks show the superior performance of the proposed method over the state-of-the-arts.

756 citations


Journal ArticleDOI
TL;DR: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT to develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy.
Abstract: Importance Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

755 citations


Journal ArticleDOI
TL;DR: Overall progress in vaccination coverage among adolescents, HPV vaccination coverage continues to lag behind Tdap and MenACWY coverage at state and national levels, but seven public health jurisdictions achieved significant increases in ≥1- or ≥3-dose HPV vaccination Coverage among females in 2014, demonstrating that substantial improvement in HPV vaccinations coverage is feasible.
Abstract: Routine immunization is recommended for adolescents aged 11-12 years by the Advisory Committee on Immunization Practices (ACIP) for protection against diseases including pertussis, meningococcal disease, and human papillomavirus (HPV)-associated cancers. To assess vaccination coverage among adolescents, CDC analyzed data collected regarding 20,827 adolescents through the 2014 National Immunization Survey-Teen (NIS-Teen). From 2013 to 2014, coverage among adolescents aged 13-17 years increased for all routinely recommended vaccines: from 84.7% to 87.6% for ≥1 tetanus-diphtheria-acellular pertussis (Tdap) vaccine dose, from 76.6% to 79.3% for ≥1 meningococcal conjugate (MenACWY) vaccine dose, from 56.7% to 60.0% and from 33.6% to 41.7% for ≥1 HPV vaccine dose among females and males, respectively.† Coverage differed by state and local area. Despite overall progress in vaccination coverage among adolescents, HPV vaccination coverage continues to lag behind Tdap and MenACWY coverage at state and national levels. Seven public health jurisdictions achieved significant increases in ≥1- or ≥3-dose HPV vaccination coverage among females in 2014, demonstrating that substantial improvement in HPV vaccination coverage is feasible.

755 citations


Journal ArticleDOI
26 Feb 2016-Science
TL;DR: In this paper, the authors used both genetic mutants and blocking antibodies in mice to find that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin 17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring.
Abstract: Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.

755 citations


Proceedings ArticleDOI
07 Jun 2015
TL;DR: This paper proposes to apply visual attention to fine-grained classification task using deep neural network and achieves the best accuracy under the weakest supervision condition, and is competitive against other methods that rely on additional annotations.
Abstract: Fine-grained classification is challenging because categories can only be discriminated by subtle and local differences. Variances in the pose, scale or rotation usually make the problem more difficult. Most fine-grained classification systems follow the pipeline of finding foreground object or object parts (where) to extract discriminative features (what).

755 citations


Journal ArticleDOI
09 Sep 2016-Science
TL;DR: This work identifies six biological mechanisms that commonly shape responses to climate change yet are too often missing from current predictive models and prioritize the types of information needed to inform each of these mechanisms, and suggests proxies for data that are missing or difficult to collect.
Abstract: BACKGROUND As global climate change accelerates, one of the most urgent tasks for the coming decades is to develop accurate predictions about biological responses to guide the effective protection of biodiversity. Predictive models in biology provide a means for scientists to project changes to species and ecosystems in response to disturbances such as climate change. Most current predictive models, however, exclude important biological mechanisms such as demography, dispersal, evolution, and species interactions. These biological mechanisms have been shown to be important in mediating past and present responses to climate change. Thus, current modeling efforts do not provide sufficiently accurate predictions. Despite the many complexities involved, biologists are rapidly developing tools that include the key biological processes needed to improve predictive accuracy. The biggest obstacle to applying these more realistic models is that the data needed to inform them are almost always missing. We suggest ways to fill this growing gap between model sophistication and information to predict and prevent the most damaging aspects of climate change for life on Earth. ADVANCES On the basis of empirical and theoretical evidence, we identify six biological mechanisms that commonly shape responses to climate change yet are too often missing from current predictive models: physiology; demography, life history, and phenology; species interactions; evolutionary potential and population differentiation; dispersal, colonization, and range dynamics; and responses to environmental variation. We prioritize the types of information needed to inform each of these mechanisms and suggest proxies for data that are missing or difficult to collect. We show that even for well-studied species, we often lack critical information that would be necessary to apply more realistic, mechanistic models. Consequently, data limitations likely override the potential gains in accuracy of more realistic models. Given the enormous challenge of collecting this detailed information on millions of species around the world, we highlight practical methods that promote the greatest gains in predictive accuracy. Trait-based approaches leverage sparse data to make more general inferences about unstudied species. Targeting species with high climate sensitivity and disproportionate ecological impact can yield important insights about future ecosystem change. Adaptive modeling schemes provide a means to target the most important data while simultaneously improving predictive accuracy. OUTLOOK Strategic collections of essential biological information will allow us to build generalizable insights that inform our broader ability to anticipate species’ responses to climate change and other human-caused disturbances. By increasing accuracy and making uncertainties explicit, scientists can deliver improved projections for biodiversity under climate change together with characterizations of uncertainty to support more informed decisions by policymakers and land managers. Toward this end, a globally coordinated effort to fill data gaps in advance of the growing climate-fueled biodiversity crisis offers substantial advantages in efficiency, coverage, and accuracy. Biologists can take advantage of the lessons learned from the Intergovernmental Panel on Climate Change’s development, coordination, and integration of climate change projections. Climate and weather projections were greatly improved by incorporating important mechanisms and testing predictions against global weather station data. Biology can do the same. We need to adopt this meteorological approach to predicting biological responses to climate change to enhance our ability to mitigate future changes to global biodiversity and the services it provides to humans.

755 citations


Posted Content
TL;DR: The initial COVID-19 open image data collection was created by assembling medical images from websites and publications and currently contains 123 frontal view X-rays.
Abstract: This paper describes the initial COVID-19 open image data collection. It was created by assembling medical images from websites and publications and currently contains 123 frontal view X-rays.

755 citations


01 Dec 2015
TL;DR: Data is presented for maternal age, live-birth order, race and Hispanic origin, marital status, attendant at birth, method of delivery, period of gestation, birthweight, and plurality.
Abstract: This report presents 2014 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal age, live-birth order, race and Hispanic origin, marital status, attendant at birth, method of delivery, period of gestation, birthweight, and plurality. Birth and fertility rates are presented by age, live-birth order, race and Hispanic origin, and marital status. Selected data by mother's state of residence and birth rates by age and race of father also are shown. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.

Journal ArticleDOI
TL;DR: It is found that the impacts of dietary changes toward less meat and more plant-based diets vary greatly among regions, and the largest absolute environmental and health benefits result from diet shifts in developing countries whereas Western high-income and middle-income countries gain most in per capita terms.
Abstract: What we eat greatly influences our personal health and the environment we all share. Recent analyses have highlighted the likely dual health and environmental benefits of reducing the fraction of animal-sourced foods in our diets. Here, we couple for the first time, to our knowledge, a region-specific global health model based on dietary and weight-related risk factors with emissions accounting and economic valuation modules to quantify the linked health and environmental consequences of dietary changes. We find that the impacts of dietary changes toward less meat and more plant-based diets vary greatly among regions. The largest absolute environmental and health benefits result from diet shifts in developing countries whereas Western high-income and middle-income countries gain most in per capita terms. Transitioning toward more plant-based diets that are in line with standard dietary guidelines could reduce global mortality by 6–10% and food-related greenhouse gas emissions by 29–70% compared with a reference scenario in 2050. We find that the monetized value of the improvements in health would be comparable with, or exceed, the value of the environmental benefits although the exact valuation method used considerably affects the estimated amounts. Overall, we estimate the economic benefits of improving diets to be 1–31 trillion US dollars, which is equivalent to 0.4–13% of global gross domestic product (GDP) in 2050. However, significant changes in the global food system would be necessary for regional diets to match the dietary patterns studied here.

Journal ArticleDOI
TL;DR: The declines in thyroid cancer mortality reflect both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the incidence are likely due to the increase in the detection of this neoplasm over the last few decades.
Abstract: In most areas of the world, thyroid cancer incidence has been appreciably increasing over the last few decades, whereas mortality has steadily declined. We updated global trends in thyroid cancer mortality and incidence using official mortality data from the World Health Organization (1970-2012) and incidence data from the Cancer Incidence in Five Continents (1960-2007). Male mortality declined in all the major countries considered, with annual percent changes around -2/-3% over the last decades. Only in the United States mortality declined up to the mid 1980s and increased thereafter. Similarly, in women mortality declined in most countries considered, with APCs around -2/-5% over the last decades, with the exception of the UK, the United States and Australia, where mortality has been declining up to the late 1980s/late 1990s to level off (or increase) thereafter. In 2008-2012, most countries had mortality rates (age-standardized, world population) between 0.20 and 0.40/100,000 men and 0.20 and 0.60/100,000 women, the highest rates being in Latvia, Hungary, the Republic of Moldova and Israel (over 0.40/100,000) for men and in Ecuador, Colombia and Israel (over 0.60/100,000) for women. In most countries, a steady increase in the incidence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes. The declines in thyroid cancer mortality reflect both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the incidence are likely due to the increase in the detection of this neoplasm over the last few decades.

Journal ArticleDOI
24 Jan 2017-JAMA
TL;DR: Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA1c level during 24 weeks.
Abstract: Importance Previous clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection. Objective To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections. Design, Setting, and Participants Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A 1c (HbA 1c ) levels of 7.5% to 9.9%. Interventions Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53). Main Outcomes and Measures Primary outcome measure was the difference in change in central-laboratory–measured HbA 1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks. Results Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA 1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA 1c reduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P 1c level from baseline was –0.6% (95% CI, –0.8% to –0.3%; P P = .002). Severe hypoglycemia events occurred in 2 participants in each group. Conclusions and Relevance Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA 1c level during 24 weeks. Further research is needed to assess longer-term effectiveness, as well as clinical outcomes and adverse effects. Trial Registration clinicaltrials.gov Identifier:NCT02282397

Journal ArticleDOI
TL;DR: In this article, the Weyl semimetal state in an inversion-symmetry-breaking single-crystalline solid, Niobium arsenide (NbAs), has been discovered.
Abstract: Three types of fermions play a fundamental role in our understanding of nature: Dirac, Majorana and Weyl. Whereas Dirac fermions have been known for decades, the latter two have not been observed as any fundamental particle in high-energy physics, and have emerged as a much-sought-out treasure in condensed matter physics. A Weyl semimetal is a novel crystal whose low-energy electronic excitations behave as Weyl fermions. It has received worldwide interest and is believed to open the next era of condensed matter physics after graphene and three-dimensional topological insulators. However, experimental research has been held back because Weyl semimetals are extremely rare in nature. Here, we present the experimental discovery of the Weyl semimetal state in an inversion-symmetry-breaking single-crystalline solid, niobium arsenide (NbAs). Utilizing the combination of soft X-ray and ultraviolet photoemission spectroscopy, we systematically study both the surface and bulk electronic structure of NbAs. We experimentally observe both the Weyl cones in the bulk and the Fermi arcs on the surface of this system. Our ARPES data, in agreement with our theoretical band structure calculations, identify the Weyl semimetal state in NbAs, which provides a real platform to test the potential of Weyltronics. Experiments show that niobium arsenide is a Weyl semimetal.

Journal ArticleDOI
TL;DR: In this article, the authors discuss how and why social media platforms have become powerful sites for documenting and challenging episodes of police brutality and the misrepresentation of racialized bodies in mainstream media.
Abstract: As thousands of demonstrators took to the streets of Ferguson, Missouri, to protest the fatal police shooting of unarmed African American teenager Michael Brown in the summer of 2014, news and commentary on the shooting, the protests, and the militarized response that followed circulated widely through social media networks. Through a theorization of hashtag usage, we discuss how and why social media platforms have become powerful sites for documenting and challenging episodes of police brutality and the misrepresentation of racialized bodies in mainstream media. We show how engaging in “hashtag activism” can forge a shared political temporality, and, additionally, we examine how social media platforms can provide strategic outlets for contesting and reimagining the materiality of racialized bodies. Our analysis combines approaches from linguistic anthropology and social movements research to investigate the semiotics of digital protest and to interrogate both the possibilities and the pitfalls of engaging in “hashtag ethnography.”

Journal ArticleDOI
TL;DR: The method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone, and identifies a spectrum of subpopulations defined by differences in chromatin signatures of pluripotency and differentiation priming.
Abstract: Chromatin profiling provides a versatile means to investigate functional genomic elements and their regulation. However, current methods yield ensemble profiles that are insensitive to cell-to-cell variation. Here we combine microfluidics, DNA barcoding and sequencing to collect chromatin data at single-cell resolution. We demonstrate the utility of the technology by assaying thousands of individual cells and using the data to deconvolute a mixture of ES cells, fibroblasts and hematopoietic progenitors into high-quality chromatin state maps for each cell type. The data from each single cell are sparse, comprising on the order of 1,000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of subpopulations defined by differences in chromatin signatures of pluripotency and differentiation priming. We corroborate these findings by comparison to orthogonal single-cell gene expression data. Our method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone.

Journal ArticleDOI
TL;DR: The molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host and minimum effective concentration must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.
Abstract: Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.

Journal ArticleDOI
TL;DR: The results illuminate the significant moderating impact of analytics capability–business strategy alignment on the BDAC–FPER relationship and the value of the entanglement conceptualization of the higher-order BDAC model and its impact on FPER.

Posted Content
TL;DR: A large-scale benchmark of existing state-of-the-art methods on classification problems and the effect of dataset shift on accuracy and calibration is presented, finding that traditional post-hoc calibration does indeed fall short, as do several other previous methods.
Abstract: Modern machine learning methods including deep learning have achieved great success in predictive accuracy for supervised learning tasks, but may still fall short in giving useful estimates of their predictive {\em uncertainty}. Quantifying uncertainty is especially critical in real-world settings, which often involve input distributions that are shifted from the training distribution due to a variety of factors including sample bias and non-stationarity. In such settings, well calibrated uncertainty estimates convey information about when a model's output should (or should not) be trusted. Many probabilistic deep learning methods, including Bayesian-and non-Bayesian methods, have been proposed in the literature for quantifying predictive uncertainty, but to our knowledge there has not previously been a rigorous large-scale empirical comparison of these methods under dataset shift. We present a large-scale benchmark of existing state-of-the-art methods on classification problems and investigate the effect of dataset shift on accuracy and calibration. We find that traditional post-hoc calibration does indeed fall short, as do several other previous methods. However, some methods that marginalize over models give surprisingly strong results across a broad spectrum of tasks.

Journal ArticleDOI
TL;DR: New classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups, and have been partially validated and generally perform better than existing criteria.
Abstract: Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of Conclusions The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Proceedings ArticleDOI
Xinlei Chen1, Kaiming He1
01 Jun 2021
TL;DR: SimSiam as discussed by the authors proposes to use a stop-gradient operation to prevent collapsing solutions in Siamese networks, which achieves competitive results on ImageNet and downstream tasks, and further shows proof-of-concept experiments verifying it.
Abstract: Siamese networks have become a common structure in various recent models for unsupervised visual representation learning. These models maximize the similarity between two augmentations of one image, subject to certain conditions for avoiding collapsing solutions. In this paper, we report surprising empirical results that simple Siamese networks can learn meaningful representations even using none of the following: (i) negative sample pairs, (ii) large batches, (iii) momentum encoders. Our experiments show that collapsing solutions do exist for the loss and structure, but a stop-gradient operation plays an essential role in preventing collapsing. We provide a hypothesis on the implication of stop-gradient, and further show proof-of-concept experiments verifying it. Our "SimSiam" method achieves competitive results on ImageNet and downstream tasks. We hope this simple baseline will motivate people to rethink the roles of Siamese architectures for unsupervised representation learning. Code is made available.1

Journal ArticleDOI
24 Oct 2017-JAMA
TL;DR: It is suggested that robotic-assisted laparoscopic surgery, when performed by surgeons with varying experience with robotic surgery, does not confer an advantage in rectal cancer resection.
Abstract: Importance Robotic rectal cancer surgery is gaining popularity, but limited data are available regarding safety and efficacy. Objective To compare robotic-assisted vs conventional laparoscopic surgery for risk of conversion to open laparotomy among patients undergoing resection for rectal cancer. Design, Setting, and Participants Randomized clinical trial comparing robotic-assisted vs conventional laparoscopic surgery among 471 patients with rectal adenocarcinoma suitable for curative resection conducted at 29 sites across 10 countries, including 40 surgeons. Recruitment of patients was from January 7, 2011, to September 30, 2014, follow-up was conducted at 30 days and 6 months, and final follow-up was on June 16, 2015. Interventions Patients were randomized to robotic-assisted (n = 237) or conventional (n = 234) laparoscopic rectal cancer resection, performed by either high (upper rectum) or low (total rectum) anterior resection or abdominoperineal resection (rectum and perineum). Main Outcomes and Measures The primary outcome was conversion to open laparotomy. Secondary end points included intraoperative and postoperative complications, circumferential resection margin positivity (CRM+) and other pathological outcomes, quality of life (36-Item Short Form Survey and 20-item Multidimensional Fatigue Inventory), bladder and sexual dysfunction (International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index), and oncological outcomes. Results Among 471 randomized patients (mean [SD] age, 64.9 [11.0] years; 320 [67.9%] men), 466 (98.9%) completed the study. The overall rate of conversion to open laparotomy was 10.1%: 19 of 236 patients (8.1%) in the robotic-assisted laparoscopic group and 28 of 230 patients (12.2%) in the conventional laparoscopic group (unadjusted risk difference = 4.1% [95% CI, −1.4% to 9.6%]; adjusted odds ratio = 0.61 [95% CI, 0.31 to 1.21];P = .16). The overall CRM+ rate was 5.7%; CRM+ occurred in 14 (6.3%) of 224 patients in the conventional laparoscopic group and 12 (5.1%) of 235 patients in the robotic-assisted laparoscopic group (unadjusted risk difference = 1.1% [95% CI, −3.1% to 5.4%]; adjusted odds ratio = 0.78 [95% CI, 0.35 to 1.76];P = .56). Of the other 8 reported prespecified secondary end points, including intraoperative complications, postoperative complications, plane of surgery, 30-day mortality, bladder dysfunction, and sexual dysfunction, none showed a statistically significant difference between groups. Conclusions and Relevance Among patients with rectal adenocarcinoma suitable for curative resection, robotic-assisted laparoscopic surgery, as compared with conventional laparoscopic surgery, did not significantly reduce the risk of conversion to open laparotomy. These findings suggest that robotic-assisted laparoscopic surgery, when performed by surgeons with varying experience with robotic surgery, does not confer an advantage in rectal cancer resection. Trial Registration isrctn.org Identifier:ISRCTN80500123

Proceedings ArticleDOI
31 Dec 2015
TL;DR: This system is capable of capturing comprehensive dense globally consistent surfel-based maps of room scale environments explored using an RGB-D camera in an incremental online fashion, without pose graph optimisation or any postprocessing steps.
Abstract: We present a novel approach to real-time dense visual SLAM. Our system is capable of capturing comprehensive dense globally consistent surfel-based maps of room scale environments explored using an RGB-D camera in an incremental online fashion, without pose graph optimisation or any postprocessing steps. This is accomplished by using dense frame-tomodel camera tracking and windowed surfel-based fusion coupled with frequent model refinement through non-rigid surface deformations. Our approach applies local model-to-model surface loop closure optimisations as often as possible to stay close to the mode of the map distribution, while utilising global loop closure to recover from arbitrary drift and maintain global consistency.

Posted Content
TL;DR: In this article, the discovery and stable generation of temporal dissipative Kerr solitons in continuous-wave (CW) laser driven optical microresonators is described and analytical and numerical descriptions are presented that do not only reproduce qualitative features but can also be used to accurately model and predict the characteristics of experimental systems.
Abstract: This chapter describes the discovery and stable generation of temporal dissipative Kerr solitons in continuous-wave (CW) laser driven optical microresonators. The experimental signatures as well as the temporal and spectral characteristics of this class of bright solitons are discussed. Moreover, analytical and numerical descriptions are presented that do not only reproduce qualitative features but can also be used to accurately model and predict the characteristics of experimental systems. Particular emphasis lies on temporal dissipative Kerr solitons with regard to optical frequency comb generation where they are of particular importance. Here, one example is spectral broadening and self-referencing enabled by the ultra-short pulsed nature of the solitons. Another example is dissipative Kerr soliton formation in integrated on-chip microresonators where the emission of a dispersive wave allows for the direct generation of unprecedentedly broadband and coherent soliton spectra with smooth spectral envelope.

Journal ArticleDOI
TL;DR: Emerging evidence that the microbiome extends its influence to the brain via various pathways connecting the gut to the central nervous system is highlighted.

Journal ArticleDOI
09 Apr 2019-BMJ
TL;DR: PHQ-9 sensitivity compared with semistructured diagnostic interviews was greater than in previous conventional meta-analyses that combined reference standards, and a cut-off score of 10 or above maximized combined sensitivity and specificity overall and for subgroups.
Abstract: Objective To determine the accuracy of the Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression. Design Individual participant data meta-analysis. Data sources Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-February 2015). Inclusion criteria Eligible studies compared PHQ-9 scores with major depression diagnoses from validated diagnostic interviews. Primary study data and study level data extracted from primary reports were synthesized. For PHQ-9 cut-off scores 5-15, bivariate random effects meta-analysis was used to estimate pooled sensitivity and specificity, separately, among studies that used semistructured diagnostic interviews, which are designed for administration by clinicians; fully structured interviews, which are designed for lay administration; and the Mini International Neuropsychiatric (MINI) diagnostic interviews, a brief fully structured interview. Sensitivity and specificity were examined among participant subgroups and, separately, using meta-regression, considering all subgroup variables in a single model. Results Data were obtained for 58 of 72 eligible studies (total n=17 357; major depression cases n=2312). Combined sensitivity and specificity was maximized at a cut-off score of 10 or above among studies using a semistructured interview (29 studies, 6725 participants; sensitivity 0.88, 95% confidence interval 0.83 to 0.92; specificity 0.85, 0.82 to 0.88). Across cut-off scores 5-15, sensitivity with semistructured interviews was 5-22% higher than for fully structured interviews (MINI excluded; 14 studies, 7680 participants) and 2-15% higher than for the MINI (15 studies, 2952 participants). Specificity was similar across diagnostic interviews. The PHQ-9 seems to be similarly sensitive but may be less specific for younger patients than for older patients; a cut-off score of 10 or above can be used regardless of age.. Conclusions PHQ-9 sensitivity compared with semistructured diagnostic interviews was greater than in previous conventional meta-analyses that combined reference standards. A cut-off score of 10 or above maximized combined sensitivity and specificity overall and for subgroups. Registration PROSPERO CRD42014010673.

Journal ArticleDOI
TL;DR: The aim of this review article is to provide an overview of GANs for the signal processing community, drawing on familiar analogies and concepts where possible, and point to remaining challenges in their theory and application.
Abstract: Generative adversarial networks (GANs) provide a way to learn deep representations without extensively annotated training data. They achieve this through deriving backpropagation signals through a competitive process involving a pair of networks. The representations that can be learned by GANs may be used in a variety of applications, including image synthesis, semantic image editing, style transfer, image super-resolution and classification. The aim of this review paper is to provide an overview of GANs for the signal processing community, drawing on familiar analogies and concepts where possible. In addition to identifying different methods for training and constructing GANs, we also point to remaining challenges in their theory and application.

Journal ArticleDOI
01 Jun 2019-Brain
TL;DR: A recently recognized brain disorder that mimics the clinical features of Alzheimer’s disease: Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).
Abstract: We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the 'oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.

Journal ArticleDOI
TL;DR: A simple yet powerful deep network architecture, U2-Net, for salient object detection (SOD), a two-level nested U-structure that enables us to train a deep network from scratch without using backbones from image classification tasks.