We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide ...representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person-years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person-years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85–1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year-olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age.
•We show deep learning to extract features from structured tabular data.•We apply information-fusion-based sensitivity analysis to feature importance.•Deep learning-based features enable more ...accurate classification of trader risk.•Deep learning-based risk management increases profits in our case study.
The paper examines the potential of deep learning to support decisions in financial risk management. We develop a deep learning model for predicting whether individual spread traders secure profits from future trades. This task embodies typical modeling challenges faced in risk and behavior forecasting. Conventional machine learning requires data that is representative of the feature-target relationship and relies on the often costly development, maintenance, and revision of handcrafted features. Consequently, modeling highly variable, heterogeneous patterns such as trader behavior is challenging. Deep learning promises a remedy. Learning hierarchical distributed representations of the data in an automatic manner (e.g. risk taking behavior), it uncovers generative features that determine the target (e.g., trader’s profitability), avoids manual feature engineering, and is more robust toward change (e.g. dynamic market conditions). The results of employing a deep network for operational risk forecasting confirm the feature learning capability of deep learning, provide guidance on designing a suitable network architecture and demonstrate the superiority of deep learning over machine learning and rule-based benchmarks.
Inhibiting the protein–protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, ...including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1−Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood–brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1−Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonanceand further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1−Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.
Summary
Background
Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk ...estimation.
Aim
To validate the OLGA and OLGIM staging systems in a region with high risk of GC.
Methods
This retrospective study included 474 GC patients and age‐ and sex‐matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis.
Results
More GC patients had OLGA stages III–IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal‐type GCs (62.2%) compared with diffuse‐type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively in multivariate analysis. The association was more significant for intestinal‐type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse‐type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal‐type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse‐type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend.
Conclusion
As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high‐risk regions, especially for intestinal‐type gastric cancer.
► Grilled and roasted beef and pork contained PAHs. ► PAHs levels in beef and pork depend on method of cooking and type of heat source used. ► High levels of PAHs were found in charcoal grilled pork. ...► Charcoal grilling of pork resulted in extremely high levels of benzo(a)pyrene.
The concentrations of seven polycyclic aromatic hydrocarbons (PAHs) viz. chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, dibenzo(a,h)anthracene, benzo(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene in 150 samples of commercial meat products were determined. The PAHs were extracted with hexane, purified with Sep-Pak Florisil cartridges and determined by high-performance liquid chromatography using a fluorescence detector. Levels of PAHs were dependent on the method of cooking and type of heat source used. Relatively high levels of PAHs, 10.2μg/kg on average, were found in charcoal-grilled pork samples. Average PAH levels in beef did not exceed 0.80μg/kg. Charcoal grilling of pork samples resulted in extremely high levels of benzo(a)pyrene (3.0μg/kg), while the average benzo(a)pyrene levels in charcoal-grilled beef samples were 0.15μg/kg. These data can be used to estimate the dietary exposure of consumers to PAHs and to assess any potential risk associated with the ingestion of these foods.
The Jupiter Energetic Particle Detector Instruments (JEDI) on the Juno Jupiter polar-orbiting, atmosphere-skimming, mission to Jupiter will coordinate with the several other space physics instruments ...on the Juno spacecraft to characterize and understand the space environment of Jupiter’s polar regions, and specifically to understand the generation of Jupiter’s powerful aurora. JEDI comprises 3 nearly-identical instruments and measures at minimum the energy, angle, and ion composition distributions of ions with energies from H:20 keV and O: 50 keV to >1 MeV, and the energy and angle distribution of electrons from <40 to >500 keV. Each JEDI instrument uses microchannel plates (MCP) and thin foils to measure the times of flight (TOF) of incoming ions and the pulse height associated with the interaction of ions with the foils, and it uses solid state detectors (SSD’s) to measure the total energy (
E
) of both the ions and the electrons. The MCP anodes and the SSD arrays are configured to determine the directions of arrivals of the incoming charged particles. The instruments also use fast triple coincidence and optimum shielding to suppress penetrating background radiation and incoming UV foreground. Here we describe the science objectives of JEDI, the science and measurement requirements, the challenges that the JEDI team had in meeting these requirements, the design and operation of the JEDI instruments, their calibrated performances, the JEDI inflight and ground operations, and the initial measurements of the JEDI instruments in interplanetary space following the Juno launch on 5 August 2011. Juno will begin its prime science operations, comprising 32 orbits with dimensions 1.1×40 RJ, in mid-2016.
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct ...patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
Background. The COVID-19 pandemic is expected to have a substantial impact on people with an intellectual disability. The goal of the current study was to explore the experiences and needs of people ...with a mild intellectual disability during the COVID-19 lockdown period in the Netherlands.
Method. A descriptive qualitative methodology was conducted, using semi-structured individual interviews with six people with a mild intellectual disability. Data were analysed thematically.
Results. Three overarching themes were found: (i) Missing social contact and having people close; (ii) Being housebound has changed my daily life; and (iii) Hard to understand the preventive measures.
Conclusions. Important insights into the experiences and needs of people with a mild intellectual disability during the COVID-19 lockdown period were gained. These insights are valuable with respect to a potential second COVID-19 wave or a future infection-outbreak.
Summary Hepatic failure is a feared complication that accounts for up to 75% of mortality after extensive liver resection. Despite improved perioperative care, the increasing complexity and ...extensiveness of surgical interventions, in combination with an expanding number of resections in patients with compromised liver function, still results in an incidence of postresectional liver failure (PLF) of 1–9%. Preventive measures aim to enhance future remnant liver size and function. Numerous non-invasive techniques to assess liver function and predict remnant liver volume are being developed, along with introduction of novel surgical strategies that augment growth of the future remnant liver. Detection of PLF is often too late and treatment is primarily symptomatic. Current therapeutic research focuses on (bioartificial) liver function support and regenerative medicine. In this review we discuss the current state and new developments in prediction, prevention and management of PLF, in light of novel insights into the aetiology of this complex syndrome. Lay summary Liver failure is the main cause of death after partial liver resection for cancer, and is presumably caused by an insufficient quantity and function of the liver remnant. Detection of liver failure is often too late, and current treatment focuses on relieve of symptoms. New research initiatives explore artificial support of liver function and stimulation of regrowth of the remnant liver.
Widefield calcium imaging enables recording of large-scale neural activity across the mouse dorsal cortex. In order to examine the relationship of these neural signals to the resulting behavior, it ...is critical to demix the recordings into meaningful spatial and temporal components that can be mapped onto well-defined brain regions. However, no current tools satisfactorily extract the activity of the different brain regions in individual mice in a data-driven manner, while taking into account mouse-specific and preparation-specific differences. Here, we introduce Localized semi-Nonnegative Matrix Factorization (LocaNMF), a method that efficiently decomposes widefield video data and allows us to directly compare activity across multiple mice by outputting mouse-specific localized functional regions that are significantly more interpretable than more traditional decomposition techniques. Moreover, it provides a natural subspace to directly compare correlation maps and neural dynamics across different behaviors, mice, and experimental conditions, and enables identification of task- and movement-related brain regions.
PDF
