Miracle-dz/UniFAR-FTUs huggingface dataset:
A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders.

OBJECTIVE The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens. METHODS Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed. RESULTS Participants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high. CONCLUSIONS This is the first randomized controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02499029.
Telomere content measurement in human hematopoietic cells: Comparative analysis of qPCR and Flow‐FISH techniques

Abnormal telomere lengths have been linked to cancer and other hematologic disorders. Determination of mean telomere content (MTC) is traditionally performed by Southern blotting and densitometry, giving a mean telomere restriction fragment (TRF) value for the total cell population studied. Here, we compared a quantitative Polymerase Chain Reaction approach (qPCR) and a flow cytometric approach, fluorescence in situ hybridization (Flow‐FISH), to evaluate telomere content distribution in total patient peripheral blood mononuclear cells or specific cell populations. Flow‐FISH is based on in situ hybridization using a fluorescein‐labeled peptide nucleic acid (PNA) (CCCTAA)3 probe and DNA staining with propidium iodide. We showed that both qPCR and Flow‐FISH provide a robust measurement, with Flow‐FISH measuring a relative content longer than qPCR at a single cell approach and that TRF2 fluorescence intensity did not correlate with MTC. Both methods showed comparable telomere content reduction with age, and the rate of relative telomere loss was similar. Published 2016 Wiley Periodicals Inc. This article is a US government work and, as such, is in the public domain in the United States of America.
Assessment of EGM2008 in Europe using accurate astrogeodetic vertical deflections and omission error estimates from SRTM/DTM2006.0 residual terrain model data

[1] We assess the new EGM2008 Earth gravitational model using a set of 1056 astrogeodetic vertical deflections over parts of continental Europe. Our astrogeodetic vertical deflection data set originates from zenith camera observations performed during 1983–2008. This set, which is completely independent from EGM2008, covers, e.g., Switzerland, Germany, Portugal and Greece, and samples a variety of topography – level terrain, medium elevated and rugged Alpine areas. We describe how EGM2008 is used to compute vertical deflections according to Helmert's (surface) definition. Particular attention is paid to estimating the EGM2008 signal omission error from residual terrain model (RTM) data. The RTM data is obtained from the Shuttle Radar Topography Mission (SRTM) elevation model and the DTM2006.0 high degree spherical harmonic reference surface. The comparisons between the astrogeodetic and EGM2008 vertical deflections show an agreement of about 3 arc seconds (root mean square, RMS). Adding omission error estimates from RTM to EGM2008 significantly reduces the discrepancies from the complete European set of astrogeodetic deflections to 1 arc second (RMS). Depending on the region, the RMS errors vary between 0.4 and 1.5 arc seconds. These values not only reflect EGM2008 commission errors, but also short-scale mass-density anomalies not modelled from the RTM data. Given (1) formally stated EGM2008 commission error estimates of about 0.6–0.8 arc seconds for vertical deflections, and (2) that short-scale mass-density anomalies may affect vertical deflections by about 1 arc second, the agreement between EGM2008 and our astrogeodetic deflection data set is very good. Further focus is placed on the investigation of the high-degree spectral bands of EGM2008. As a general conclusion, EGM2008 – enhanced by RTM data – is capable of predicting Helmert vertical deflections at the 1 arc second accuracy level over Europe.
Impact of a Shared Decision Making Intervention on Health Care Utilization: A Secondary Analysis of the Chest Pain Choice Multicenter Randomized Trial

BACKGROUND Patients at low risk for acute coronary syndrome are frequently admitted for observation and cardiac testing, resulting in substantial burden and cost to the patient and the health care system. OBJECTIVES The purpose of this investigation was to measure the effect of the Chest Pain Choice (CPC) decision aid on overall health care utilization as well as utilization of specific services both during the index emergency department (ED) visit and in the subsequent 45 days. METHODS This was a planned secondary analysis of data from a pragmatic multicenter randomized trial of shared decision making in adults presenting to the ED with chest pain who were being considered for observation unit admission for cardiac stress testing or coronary computed tomography angiography. The trial compared an intervention group engaged in shared decision making facilitated by the CPC decision aid to a control group receiving usual care. Hospital-level billing data were used to measure utilization for the index ED visit and during the following 45 days. Patients in both groups also were asked to keep a diary recording health care utilization over the same 45-day period. Outcomes assessed included length of time in the ED and observation, ED visits, office visits, hospitalizations, testing, imaging, and procedures. RESULTS Of the 898 patients included in the original trial, we were able to contact 834 (92.9%) patients for 45-day health care diary review. There was no difference in patient-reported health care utilization between the study arms. Hospital-level billing data were obtained for all 898 (100%) patients. During the initial ED visit the length of stay (LOS) was similar, and there was no difference in the frequency of observation unit admission between study arms. However, the mean observation unit LOS was 95 minutes (95% confidence interval [CI] = 40.8-149.8) shorter in the CPC arm and the mean number of tests was lower in the CPC arm (decrease in 19.4 imaging studies per 100 patients, 95% CI = 15.5-23.3). When evaluating the entire encounter and follow-up period, the intervention arm underwent fewer tests (decrease in 125.6 tests per 100 patients, 95% CI = 29.3-221.6). More specifically, there were fewer advanced cardiac imaging tests completed (25.8 fewer per 100 patients, 95% CI = 3.74-47.9) in the intervention arm. CONCLUSIONS Shared decision making in low-risk chest pain can lead to decreased diagnostic testing without worsening outcomes measured over 45 days.
PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8+ T-Cell–Driven Antitumor Immunity

Purpose: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti–PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb). Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models. Global transcriptional profiling and flow cytometry analysis were used to delineate mechanisms underpinning the observed synergy. Results: PD-1/PD-L1 blockade and agonist anti-CD27 mAb synergize for increased CD8+ T-cell expansion and effector function, exemplified by enhanced IFNγ, TNFα, granzyme B, and T-bet. Transcriptome analysis of CD8+ T cells revealed that combination therapy triggered a convergent program largely driven by IL2 and Myc. However, division of labor was also apparent such that anti–PD-1/L1 activates a cytotoxicity–gene expression program whereas anti-CD27 preferentially augments proliferation. In tumor models, either dependent on endogenous CD8+ T cells or adoptive transfer of transgenic T cells, anti-CD27 mAb synergized with PD-1/L1 blockade for antitumor immunity. Finally, we show that a clinically relevant anti-human CD27 mAb, varlilumab, similarly synergizes with PD-L1 blockade for protection against lymphoma in human–CD27 transgenic mice. Conclusions: Our findings suggest that suboptimal T-cell invigoration in cancer patients undergoing treatment with PD-1 checkpoint blockers will be improved by dual PD-1 blockade and CD27 agonism and provide mechanistic insight into how these approaches cooperate for CD8+ T-cell activation. Clin Cancer Res; 24(10); 2383–94. ©2018 AACR.
Non-linear auto-regressive models for cross-frequency coupling in neural time series

We address the issue of reliably detecting and quantifying cross-frequency coupling (CFC) in neural time series. Based on non-linear auto-regressive models, the proposed method provides a generative and parametric model of the time-varying spectral content of the signals. As this method models the entire spectrum simultaneously, it avoids the pitfalls related to incorrect filtering or the use of the Hilbert transform on wide-band signals. As the model is probabilistic, it also provides a score of the model “goodness of fit” via the likelihood, enabling easy and legitimate model selection and parameter comparison; this data-driven feature is unique to our model-based approach. Using three datasets obtained with invasive neurophysiological recordings in humans and rodents, we demonstrate that these models are able to replicate previous results obtained with other metrics, but also reveal new insights such as the influence of the amplitude of the slow oscillation. Using simulations, we demonstrate that our parametric method can reveal neural couplings with shorter signals than non-parametric methods. We also show how the likelihood can be used to find optimal filtering parameters, suggesting new properties on the spectrum of the driving signal, but also to estimate the optimal delay between the coupled signals, enabling a directionality estimation in the coupling. Author Summary Neural oscillations synchronize information across brain areas at various anatomical and temporal scales. Of particular relevance, slow fluctuations of brain activity have been shown to affect high frequency neural activity, by regulating the excitability level of neural populations. Such cross-frequency-coupling can take several forms. In the most frequently observed type, the power of high frequency activity is time-locked to a specific phase of slow frequency oscillations, yielding phase-amplitude-coupling (PAC). Even when readily observed in neural recordings, such non-linear coupling is particularly challenging to formally characterize. Typically, neuroscientists use band-pass filtering and Hilbert transforms with ad-hoc correlations. Here, we explicitly address current limitations and propose an alternative probabilistic signal modeling approach, for which statistical inference is fast and well-posed. To statistically model PAC, we propose to use non-linear auto-regressive models which estimate the spectral modulation of a signal conditionally to a driving signal. This conditional spectral analysis enables easy model selection and clear hypothesis-testing by using the likelihood of a given model. We demonstrate the advantage of the model-based approach on three datasets acquired in rats and in humans. We further provide novel neuroscientific insights on previously reported PAC phenomena, capturing two mechanisms in PAC: influence of amplitude and directionality estimation.
The construct validity of general and specific dimensions of personality pathology

Background Modern personality disorder (PD) theory and research attempt to distinguish transdiagnostic impairments common to all PDs from constructs that explain varied PD expression. Bifactor modeling tests such distinctions; however, the only published PD criteria bifactor analysis focused on only 6 PDs and did not examine the model's construct validity. Methods We examined the structure and construct validity of competing PD criteria models using confirmatory and exploratory factor analytic methods in 628 patients who completed structured diagnostic interviews and self-reports of personality traits and impairment. Results Relative to alternative models, two bifactor models – one confirmatory model with 10 specific factors for each PD (acceptable fit) and one exploratory model with four specific factors resembling broad personality domains (excellent fit) – fit best and were compared via connections with external criteria. General and specific factors related meaningfully and differentially to personality traits, internalizing symptoms, substance use, and multiple indices of psychosocial impairment. As hypothesized, the general factor predicted interpersonal dysfunction above and beyond other psychopathology. The general factor also correlated strongly with many pathological personality traits. Conclusions The present study supported the validity of a model with both a general PD impairment dimension and separate individual difference dimensions; however, it also indicated that currently prominent models, which assume general PD impairments and personality traits are non-overlapping, may be misspecified.
Cohort profile Cohort Profile : The Flu Watch Study

Cohort Profile: The Flu Watch Study Ellen B. Fragaszy, Charlotte Warren-Gash, Lili Wang, Andrew Copas, Oliver Dukes, W. John Edmunds, Nilu Goonetilleke, Gabrielle Harvey, Anne M. Johnson, Jana Kovar, Megan S. C. Lim, Andrew McMichael, Elizabeth R. C. Millett, Irwin Nazareth, Jonathan S. Nguyen-Van-Tam, Faiza Tabassum, John M. Watson, Fatima Wurie, Maria Zambon and Andrew C. Hayward* on behalf of the Flu Watch Group Institute of Health Informatics, University College London, London, UK, London School of Hygiene & Tropical Medicine, London, UK, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, Research Department of Infection & Population Health, University College London, London, UK, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, CA, USA, Burnet Institute, Centre for Population Health, Melbourne, VIC, Australia, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Research Department of Primary Care and Population Health, University College London, London, UK, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK, Chief Medical Officer’s Private Office, Department of Health, London, UK and Public Health England Respiratory Virus Unit, Colindale, UK
‘Removed from humanity’: a qualitative analysis of attitudes toward abortion providers in anti-abortion individuals in Canada

Abstract Objective: The present study explores the content of abortion provider stigma. Background: Abortion stigma extends beyond women who have abortions to abortion providers. Previous analyses of anti-abortion bills and rhetoric have revealed stereotypes of abortion providers as dangerous and less trustworthy than other health professionals. Methods: We present a thematic analysis of one-on-one interviews about attitudes toward abortion providers with Canadian individuals (N = 21) holding an anti-abortion stance. Results: We found participants held two kinds of beliefs about abortion providers: (1) providers are agentic and intentional actors and (2) providers are non-agentic victims of a larger system. While the former subtype of provider was viewed with hostility and disgust, the latter was viewed with pity, with participants suggesting that restriction of abortion would be beneficial for provider well-being. Conclusion: We document a new component of abortion provider stigma: the belief that abortion providers are harmed by abortion and that they are to be pitied for this. This ‘abortion harms providers’ attitude parallels recent anti-abortion arguments that abortion harms women. These stigmatising attitudes both construct the provider as untrustworthy and unable to properly care for women.
Seasonal weather prediction as an initial value problem

Using a climate version of a regional atmospheric model, we show that the seasonal evolution of weather is dependent on the initial soil moisture and landscape specification. Coupling this model to a land-surface model, the soil moisture distribution and landscape are shown to cause a significant nonlinear interaction between vegetation growth and precipitation. These results demonstrate that seasonal weather prediction is an initial value problem. Moreover, on seasonal and longer timescales the surface characteristics such as soil moisture, leaf area index, and landcover type must be treated as dynamically evolving dependent variables, instead of prescribed parameters.
Management of Shiga toxin-associated Escherichia coli-induced haemolytic uraemic syndrome: randomized clinical trials are needed

The production of Shiga toxin by a bacterial strain is necessary for induction of enteropathogenic haemolytic uraemic syndrome (HUS). Only strains that produce the toxin are associated with HUS. These include enterohaemorrhagic Escherichia coli, Shigella dysenteriae and rarely Citrobacter freundii [1, 2]. All strains associated with haemorrhagic colitis and HUS are Gram-negative, thus producing lipopolysaccharide (LPS), which may also play a role in the pathogenesis of disease. The recent large outbreak of E. coli O104:H4, a strain with combined virulence factors characteristic of enteroaggregative E. coli as well as enterohaemorrhagic E. coli, provides additional evidence that, regardless of the bacterial background, acquirement of the bacteriophage-encoded gene for Shiga toxin 2 enhances the virulence of the strain causing haemorrhagic colitis and HUS. In this issue of NDT, Kielstein et al. [3] present a comprehensive summary of the outcome of this outbreak and the treatment options offered in 491 patients. Appropriate management of Shiga toxin-induced disease is contingent on an understanding of the pathogenesis of the disease as depicted in Figure 1. After ingestion, the bacteria may bind to the terminal ileum and follicle-associated epithelium of Peyer's patches [4]. Colonization is further enhanced by quorum sensing, a form of communication with other strains in the intestinal microflora, as well as induction by the host hormonal response including epinephrine and norepinephrine, which would presumably be secreted during haemorrhagic colitis [5]. These signals enhance bacterial colonization and the release of virulence factors. There is no evidence of bacteraemia during infection with Shiga toxin-producing E. coli. Following intestinal colonization, the disease is mediated by the systemic spread of bacterial virulence factors, of which Shiga toxin is of major importance.
Informational bird's eye view system for parking assistance

Primary goals of Advanced Driver Assistance Systems (ADAS) are increased safety and situations with no stress for all traffic participants. Parking safety is improved by presenting real-time vehicle environment to the driver (surround view, bird's eye view). Bird's eye view is 3D camera and parking sensors system which assist driver with parking. It covers all angles and alerts the driver about obstacles, thus minimizing possibility of traffic accidents. This paper presents one portable informational bird's eye view system.
Iterative Relay Scheduling With Hybrid ARQ Under Multiple User Equipment (Type II) Relay Environments

In this paper, we propose an iterative relay scheduling with hybrid ARQ (IRS-HARQ) scheme, which realizes fast jump-in/successive relaying and subframe-based decoding under the multiple user equipment (UE) relay environments applicable to the next-generation cellular systems (e.g., LTE-advanced and beyond). The proposed IRS-HARQ aims to increase the achievable data rate by iteratively scheduling a relatively better UE relay closer to the end user in a probabilistic sense, provided that the relay-to-end user link should be operated in an open-loop and transparent mode. The latter is due to the fact that not only there are no dedicated control channels between the UE relay and the end user, but also a new cell is not created. Under this open-loop and transparent mode, our proposed protocol is implemented by partially exploiting the channel state information based on the overhearing mechanism of acknowledge/negative acknowledge for HARQ. Further, the iterative scheduling enables UE-to-UE direct communication with proximity that offers spatial frequency reuse and energy saving.
Diverse responses of wild and cultivated tomato to BABA, oligandrin and Oidium neolycopersici infection

Background and Aims Current strategies for increased crop protection of susceptible tomato plants against pathogen infections include treatment with synthetic chemicals, application of natural pathogen‐derived compounds or transfer of resistance genes from wild tomato species within breeding programmes. In this study, a series of 45 genes potentially involved in defence mechanisms was retrieved from the genome sequence of inbred reference tomato cultivar Solanum lycopersicum ‘Heinz 1706’. The aim of the study was to analyse expression of these selected genes in wild and cultivated tomato plants contrasting in resistance to the biotrophic pathogen Oidium neolycopersici, the causative agent of powdery mildew. Plants were treated either solely with potential resistance inducers or by inducers together with the pathogen. Methods The resistance against O. neolycopersici infection as well as RT‐PCR‐based analysis of gene expression in response to the oomycete elicitor oligandrin and chemical agent &bgr;‐aminobutyric acid (BABA) were investigated in the highly susceptible domesticated inbred genotype Solanum lycopersicum ‘Amateur’ and resistant wild genotype Solanum habrochaites. Key Results Differences in basal expression levels of defensins, germins, &bgr;‐1,3‐glucanases, heveins, chitinases, osmotins and PR1 proteins in non‐infected and non‐elicited plants were observed between the highly resistant and susceptible genotypes. Moreover, these defence genes showed an extensive up‐regulation following O. neolycopersici infection in both genotypes. Application of BABA and elicitin induced expression of multiple defence‐related transcripts and, through different mechanisms, enhanced resistance against powdery mildew in the susceptible tomato genotype. Conclusions The results indicate that non‐specific resistance in the resistant genotype S. habrochaites resulted from high basal levels of transcripts with proven roles in defence processes. In the susceptible genotype S. lycopersicum ‘Amateur’, oligandrin‐ and BABA‐induced resistance involved different signalling pathways, with BABA‐treated leaves displaying direct activation of the ethylene‐dependent signalling pathway, in contrast to previously reported jasmonic acid‐mediated signalling for elicitins.