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Background and aims Design Setting Participants Intervention and comparator Measurement Findings Conclusion A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo.This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial.The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States.This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial.NTX + BUPN was compared with placebo over the course of the trial.MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up.Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%–17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo.For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks. [ABSTRACT FROM AUTHOR]

Here, we report recurrent focal deletions of the chr14q32.31- 32 locus, including TRAF3, a negative regulator of NF- kB signaling, in de novo diffuse large B cell lymphoma (DLBCL) (24/324 cases). Integrative analysis revealed an association between TRAF3 copy number loss with accumulation of NIK, the central noncanonical (NC) NF- kB kinase, and increased NC NF- kB pathway activity. Accordingly, TRAF3 genetic ablation in isogenic DLBCL model systems caused upregulation of NIK and enhanced NC NF- kB downstream signaling. Knockdown or pharmacological inhibition of NIK in TRAF3- deficient cells differentially impaired their proliferation and survival, suggesting an acquired onco- addiction to NC NF- kB. TRAF3 ablation also led to exacerbated secretion of the immunosuppressive cytokine IL- 10. Coculturing of TRAF3- deficient DLBCL cells with CD8+ T cells impaired the induction of Granzyme B and interferon (IFN) γ, which were restored following neutralization of IL- 10. Our findings corroborate a direct relationship between TRAF3 genetic alterations and NC NF- kB activation, and highlight NIK as a potential therapeutic target in a defined subset of DLBCL. [ABSTRACT FROM AUTHOR]

We consider the problem of matrix completion on an n × m matrix. We introduce the problem of interpretable matrix completion that aims to provide meaningful insights for the low-rank matrix using side information. We show that the problem can be reformulated as an optimization problem with a convex objective and binary variables. We design an algorithm called OptComplete, based on a novel concept of stochastic cutting planes to enable efficient scaling of the algorithm up to matrices of sizes n = 106 and m = 106. We prove that OptComplete converges to an optimal solution of the interpretable matrix completion problem with exponentially vanishing failure probability. We report experiments on both synthetic and real-world data sets that show that OptComplete has favorable scaling behavior and accuracy when compared with state-of-the-art methods for other types of matrix completion while providing insight on the factors that affect the matrix. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms—Discrete. Supplemental Material: The online appendices are available at https://doi.org/10.1287/ijoc.2022.0022. [ABSTRACT FROM AUTHOR]

Humans can learn complex functional relationships between variables from small amounts of data. In doing so, they draw on prior expectations about the form of these relationships. In three experiments, we show that people learn to adjust these expectations through experience, learning about the likely forms of the functions they will encounter. Previous work has used Gaussian processes—a statistical framework that extends Bayesian nonparametric approaches to regression—to model human function learning. We build on this work, modeling the process of learning to learn functions as a form of hierarchical Bayesian inference about the Gaussian process hyperparameters. [ABSTRACT FROM AUTHOR]

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2–4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal. [ABSTRACT FROM AUTHOR]

The increasing availability of individual-level data has led to numerous applications of individualized (or personalized) treatment rules (ITRs). Policy makers often wish to empirically evaluate ITRs and compare their relative performance before implementing them in a target population. We propose a new evaluation metric, the population average prescriptive effect (PAPE). The PAPE compares the performance of ITR with that of non-individualized treatment rule, which randomly treats the same proportion of units. Averaging the PAPE over a range of budget constraints yields our second evaluation metric, the area under the prescriptive effect curve (AUPEC). The AUPEC represents an overall performance measure for evaluation, like the area under the receiver and operating characteristic curve (AUROC) does for classification, and is a generalization of the QINI coefficient used in uplift modeling. We use Neyman's repeated sampling framework to estimate the PAPE and AUPEC and derive their exact finite-sample variances based on random sampling of units and random assignment of treatment. We extend our methodology to a common setting, in which the same experimental data are used to both estimate and evaluate ITRs. In this case, our variance calculation incorporates the additional uncertainty due to random splits of data used for cross-validation. The proposed evaluation metrics can be estimated without requiring modeling assumptions, asymptotic approximation, or resampling methods. As a result, it is applicable to any ITR including those based on complex machine learning algorithms. The open-source software package is available for implementing the proposed methodology. for this article are available online. [ABSTRACT FROM AUTHOR]

The purpose of this review is to broadly identify technological advances in supports and evaluation for individuals on the autism spectrum. Literature review with commentary on the evolving technologies supporting and/or evaluating social‐emotional, behavioral, academic, and cognitive domains. There has been an increasing synthesis of technology within the education domain. A growing body of research has investigated the potentiality and efficacy of technological interventions, specifically in the area of support for individuals on the autism spectrum. This growth must also factor in sustainability and feasibility to be practical within the school setting. Continued research is also necessary to ensure the equity of technology supporting individuals on the autism spectrum. Practitioner Points: Researchers have been investigating the utility of various modern technologies for autism assessment and intervention for over 50 years.Advances in technology have allowed researchers to develop new interventions and assessment techniques that are responsive to the needs of individuals on the autism spectrum.Applications of artificial intelligence (AI) to the assessment and treatment of autism spectrum disorder is an emerging area of research with tremendous potential for facilitating early identification and the implementation of adaptable interventions. [ABSTRACT FROM AUTHOR]

Summary: Background: Immune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune‐related adverse events (irAEs) which can impact multiple organ systems. Onco‐Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment‐related complications. Gastroenterologists must be prepared to identify and manage diverse immune‐mediated toxicities including enterocolitis, hepatitis, pancreatitis and other ICI‐induced toxicities. Aim: To provide a narrative review of the epidemiology, diagnostic evaluation and management of checkpoint inhibitor‐induced gastrointestinal and hepatic toxicities. Methods: We searched Cochrane and PubMed databases for articles published through August 2023. Results: Gastrointestinal and hepatic irAEs include most commonly enterocolitis and hepatitis, but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) and other rarer toxicities. Guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society for Medical Oncology, in combination with emerging cohort and clinical trial data, offer strategies for management of ICI toxicities. Evaluation of irAEs severity by formal classification and clinical stability, and a thorough workup for alternative etiologies which may clinically mimic irAEs underlie initial management. Treatments include corticosteroids, biologics and other immunosuppressive agents plus supportive care; decisions on dosing, timing and choice of steroid adjuncts and potential for subsequent checkpoint inhibitor dosing are nuanced and toxicity‐specific. Conclusions: Expanding clinical trial and cohort data have clarified the epidemiology and clinical characteristics of gastrointestinal, pancreatic and hepatic toxicities of ICIs. Guidelines, though valuable, remain based principally on retrospective cohort data. Quality prospective, controlled studies may refine algorithms for treatment and potential immunotherapy rechallenge. [ABSTRACT FROM AUTHOR]

The evolution of submarine canyons is primarily controlled by turbidity currents, which erode and fill them over time; however, many other hydrodynamic currents operate within canyons. Bottom currents from these other hydrodynamic processes, including internal tides, can be dominant processes, but their deposits are seldom recognized in sediment cores or the rock record. This study combines autonomous underwater vehicle swath bathymetry imagery and sub‐bottom profiles, high‐resolution sediment core analyses (X‐ray imagery and thin sections), and previously collected seabed video and flow measurements within Logan Canyon head (eastern Canada) to provide a detailed, modern record of facies associated with hydrodynamic processes in a canyon head. These results suggest that bottom currents are responsible for maintaining gullies on canyon sidewalls and an axial channel on the canyon floor. Thin sections of sediment cores reveal that muddy sand in the canyon head consists of mud aggregates and silt and fine‐grained sand, both behaving similarly in terms of flow dynamics. Three facies are present at macro‐scale and micro‐scale: laminated, partially laminated and bioturbated sandy mud. Sedimentary structures include rhythmic sand and mud aggregate couplets, planar to wavy laminations, current ripple cross‐laminations and fining‐upward successions, which are attributed to bottom currents induced by internal tides. Bioturbated facies, characterized by discrete biogenic structures and cross‐cutting relationships, predominate and overprint a mottled background. A mottled bioturbation fabric also alternates with or locally disrupts layering within the partially laminated facies. Internal tide currents, capable of bedload transport and forming ripples, were measured during a monitoring period in the canyon head, followed by rapid re‐establishment of benthos and associated biogenic structures, supporting the core interpretations. Preservation of sedimentary facies associated with these internal tides occurs when the sedimentation rate outpaces the rate of bioturbation, likely during stormier conditions on the shelf. These results represent observations of sedimentary facies associated with modern bottom currents and internal tides, and can be used to interpret similar occurrences within the rock record. [ABSTRACT FROM AUTHOR]

We introduce a stochastic version of the cutting plane method for a large class of data-driven mixed-integer nonlinear optimization (MINLO) problems. We show that under very weak assumptions, the stochastic algorithm can converge to an ϵ-optimal solution with high probability. Numerical experiments on several problems show that stochastic cutting planes is able to deliver a multiple order-of-magnitude speedup compared with the standard cutting plane method. We further experimentally explore the lower limits of sampling for stochastic cutting planes and show that, for many problems, a sampling size of O (n 3) appears to be sufficient for high-quality solutions. [ABSTRACT FROM AUTHOR]

Background: Social genomics has demonstrated altered inflammatory and type I interferon (IFN) gene expression among people experiencing chronic social adversity. Adverse social experiences such as discrimination and violence are linked to stimulant misuse and HIV, conditions that dysregulate inflammatory and innate antiviral responses, leading to increased HIV viral replication and risk of chronic diseases.Purpose: We aimed to determine whether methamphetamine (MA) use, unsuppressed HIV viral load (VL) (≥200 c/mL), and experienced intimate partner violence (IPV) (past 12 months) predicted inflammatory and type I IFN gene expression in HIV-positive Black and Latinx men who have sex with men (MSM).Methods: Participants were 147 HIV-positive Black and Latinx MSM recruited from the mSTUDY, a cohort of 561 MSM aged 18-45 in Los Angeles, CA, of whom half are HIV-positive and substance-using. Transcriptomic measures of inflammatory and type I IFN activity were derived from RNA sequencing of peripheral blood mononuclear cells and matched to urine drug tests, VL, and survey data across two time points 12 months apart. Analysis used linear random intercept modeling of MA use, unsuppressed VL, and experienced IPV on inflammatory and type I IFN expression.Results: In adjusted models, MA use predicted 27% upregulated inflammatory and 31% upregulated type I IFN expression; unsuppressed VL predicted 84% upregulated type I IFN but not inflammatory expression; and experienced IPV predicted 31% upregulated inflammatory and 26% upregulated type I IFN expression.Conclusions: In Black and Latinx MSM with HIV, MA use, unsuppressed VL, and experienced IPV predicted upregulated social genomic markers of immune functioning. [ABSTRACT FROM AUTHOR]

In this work, we use the immersed boundary method with four extensions to simulate a moving liquid–gas interface on a solid surface. We first define a moving contact line model and implements a static-dynamic friction condition at the immersed solid boundary. The dynamic contact angle is endogenous instead of prescribed, and the solid boundary can be non-stationary with respect to time. Second, we simulate both a surface tension force and a Young's force with one general equation that does not involve estimating local curvature. In the third extension, we splice liquid–gas interfaces to handle topological changes, such as the coalescence and separation of liquid droplets or gas bubbles. Finally, we re-sample liquid–gas interface markers to ensure a near-uniform distribution without exerting artificial forces. We demonstrate empirical convergence of our methods on non-trivial examples and apply them to several benchmark cases, including a slipping droplet on a wall and a rising bubble. [ABSTRACT FROM AUTHOR]

• Yield of ambulatory video-EEG monitoring varies based on the referring question. • Yield was 75 % for seizure classification and 46 % for event differentiation. • 41 % of all ambulatory video-EEG recordings captured a diagnostic event. • Unreported seizures occur frequently in the ambulatory setting. • Each day of recording adds diagnostic value, up until the end of the eighth day. Ambulatory video-electroencephalography (video-EEG) represents a low-cost, convenient and accessible alternative to inpatient video-EEG monitoring, however few studies have examined their diagnostic yield. In this large-scale retrospective study conducted in Australia, we evaluated the efficacy of prolonged ambulatory video-EEG recordings in capturing diagnostic events and resolving the referring question. Sequential adult and paediatric ambulatory video-EEG reports from April 2020 to June 2021 were reviewed retrospectively. Data collection included patient demographics, clinical information, and details of events and EEG abnormalities. Clinical utility was assessed by examining i) time to first diagnostic event, and ii) ability to resolve the referring questions – seizure localisation , quantification , classification , and differentiation (differentiating seizures from non-epileptic events). Of the 600 reports analysed, 49 % captured at least one event, and 45 % captured interictal abnormalities (epileptiform or non-epileptiform). Seizures, probable psychogenic events (mostly non-convulsive), and other non-epileptic events occurred in 13 %, 23 % and 21 % of recordings respectively, with overlap. Unreported events were captured in 53 (9 %) recordings, and unreported seizures represented more than half of all seizures captured (51 %, 392/773). Nine percent of events were missing clinical, video or electrographic data. A diagnostic event occurred in 244 (41 %) recordings, of which 14 % were captured between the fifth and eighth day of recording. Reported event frequency ≥ 1/week was the only significant predictor of diagnostic event capture. In recordings with both seizures and psychogenic events, unrecognized seizures were frequent, and seizures may be missed if recording is terminated early. The referring question was resolved in 85 % of reports with at least one event, and 53 % of all reports. Specifically, this represented 46 % of reports (235/512) for differentiation of events, and 75 % of reports (27/36) for classification of seizures. Ambulatory video-EEG recordings are of high diagnostic value in capturing clinically relevant events and resolving the referring clinical questions. [ABSTRACT FROM AUTHOR]

Waves and tidal currents can interact to produce strong seabed shear stress and mobilization of sediments on continental shelves. Modelled wave and tidal current data for a 3-year period were used in a combined-flow sediment transport model to simulate the seabed shear stresses and the mobilization of uniform medium sand on the continental shelves of Canada. The modelling results are presented to establish the first national framework of seabed disturbance and sediment mobility on the continental shelves of Canada. Strong waves and tidal currents on the Canadian continental shelves produce mean bed shear velocity >5 cm·s−1. Medium sand can be mobilized >50% of the time over many areas on the shelves. The mobilization by tidal currents occurs over 36% and by waves over 50% of the shelf area, demonstrating that mobilization of sediments is dominated by waves on the Canadian continental shelves. Combined shear stresses due to wave and tidal current interaction further increase sediment mobilization to over 68% of the shelf area. The spatial variation of the relative importance of wave and tidal disturbances allows classification of the continental shelves into six disturbance types. Innovative Seabed Disturbance (SDI) and Sediment Mobility (SMI) indices are proposed to quantify the seabed exposure to oceanographic processes and sediment mobilization, incorporating both the magnitude and frequency of these processes. The proposed SDI and SMI, together with the disturbance type classification, can be used as standard parameters to best quantify seabed disturbance and sediment mobility on other shelves of the world. [ABSTRACT FROM AUTHOR]

Anxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of α4βδ GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by α4 knock-out, suggesting that α4βδ-induced reductions in kalirin7 underlie pruning. Increased spine density due to local α4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies. [ABSTRACT FROM AUTHOR]

Mindfulness-based interventions (MBIs) may offer a means for Latinx families to ameliorate stress, enhance emotion regulation, and foster social support. We assessed pilot data from Latinx parents in Eastside Los Angeles (n = 27) matched with their children aged 10–16 (n = 32) to determine whether participation in a community-derived MBI was associated with greater improvements in dispositional mindfulness, perceived stress, emotion regulation, and family social support compared to a control condition. Compared to the control group, parents in the MBI group showed greater reductions in perceived stress scale (PSS) scores (B = − 2.94, 95% CI [− 5.58, − 0.39], p = 0.029), while their children reported greater increases in perceived social support from family (B = 2.32, 95% CI [0.26, 4.38], p = 0.027). Findings show a community-derived MBI may improve stress in Latinx parents and social support for their children. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the efficacy and safety profile of double‐balloon enteroscopy (DBE)‐assisted endoscopic retrograde cholangiopancreatography (ERCP) using a short enteroscope in patients with surgically altered anatomy. Methods: A retrospective study was performed to review the endoscopic outcomes of patients undergoing DBE‐assisted ERCP for biliary diseases in Tuen Mun and Pok Oi hospitals in Hong Kong SAR, China from December 2015 to December 2020. Results: Altogether 46 DBE‐assisted ERCP procedures were performed in 37 patients. The enteroscopic success rate, defined as reaching the papilla or bilioenteric anastomosis, was 95.7% (95% confidence interval [CI] 85.2%‐99.5%), which was significantly lower in patients with intact stomach than in those who had a previous gastrectomy (67% vs 100%, P = 0.014). The diagnostic ERCP success rate, defined as performance in an informative cholangiogram, was 84.1% (95% CI 69.9%‐93.4%) in cases where it was attempted. Intended biliary therapeutic interventions were successfully performed in 76.1% (95% CI 61.2%‐87.4%) of all procedures. Adverse events were reported in six (13.0%) procedures (95% CI 4.9%‐26.3%), including the micro‐perforation of the intestine in two (4.3%) patients with prior Roux‐en‐Y gastrectomy, three (6.5%) of acute cholangitis and one (2.2%) of acute pancreatitis. All adverse events were managed successfully using conservative methods except in one case of micro‐perforation, which required a laparotomy. Conclusions: DBE‐assisted ERCP using a short enteroscope is a promising technique for managing biliary diseases in patients with surgically altered anatomy. It must be performed to avoid perforation, particularly in patients with a Roux‐en‐Y reconstruction. [ABSTRACT FROM AUTHOR]

The article discusses the diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE). Other topics include the psychiatric symptoms of ANMDARE like psychosis and depressive symptoms, how psychiatrists can use factors like the comorbid neurologic symptoms and signs in treating ANMDARE, and the need to consider comorbid systemic illness.

Objectives: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. Methods: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. Results: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93–1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89–1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78–1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73–0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. Conclusions: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. Trial registration: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988. [ABSTRACT FROM AUTHOR]

Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population. We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19. Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary artery disease (26%), and chronic obstructive pulmonary disease (14%). Twenty patients had severe COVID-19 (34.5%) and 38 had nonsevere disease (65.5%). Severe disease was more common in older SOT recipients with comorbidities and was associated with cough, dyspnea, pneumonia, C-reactive protein >10 mg/L, and platelet count <150/μL. Sex, race, body mass index, time from transplant, baseline immunosuppression, and diagnosis month did not differ among those with severe and nonsevere COVID-19. Seventy percent of SOT recipients were hospitalized vs 27.2% of general patients with COVID-19 and inpatient SOT recipients had a higher mechanical ventilation rate. Though a trend toward longer length of stay, higher intensive care unit admission, and greater inpatient mortality was observed (19.5% vs 14.8%), these differences were not significant. The severe acute respiratory syndrome coronavirus 2 has greatly impacted SOT recipients. One-third of our SOT recipients seen during the first wave had severe illness with associated standard risk factors for poor outcome. Compared with general first-wave patients, more SOT recipients were hospitalized, although inpatient COVID-19 mortality did not significantly differ. [ABSTRACT FROM AUTHOR]

In this study, we employ a dual-objective optimization model, utilizing the Implicit Modified Coverage Location Problem (MCLP-Implicit) approach, to determine an appropriate fire station allocation. Our objectives encompass maximizing coverage in areas with a heightened projected demand, based on socioeconomic predictors of building fires, and concurrently minimizing the distance of uncovered demand zones to the closest fire station. The challenges of this model reflect the criticality of strategic placement, aiming for not just swift response times but also the complete coverage of a region with priority given to subregions with a pronounced potential for incidents. The applicability of the proposed approach is demonstrated through a case study in south-east Queensland. Our findings indicate that there is a tangible justification for adopting this model. The broader coverage and wider spread of locations it produces can greatly aid in the dynamic deployment of personnel during surges caused by seasonal fluctuations or unforeseen calamities. By weaving in socioeconomic aspects into demand predictions, our model has also maintained appropriate coverage to socioeconomically disadvantaged communities in the region. Nevertheless, it is paramount to underline the recommendation that further research should account for road connectivity—a pivotal factor when pinpointing these locations in the real world. This research paves the way for enriched insights in long-term urban planning and fire response protocol crafting, especially in regions mirroring similar socioeconomic profiles or risks of natural disasters, not to mention its commercial implications to the relevant industry servicing the fire and rescue authorities. [ABSTRACT FROM AUTHOR]

Background: Patient age is one of the most salient clinical indicators of risk from COVID-19. Age-specific distributions of known SARS-CoV-2 infections and COVID-19-related deaths are available for many regions. Less attention has been given to the age distributions of serious medical interventions administered to COVID-19 patients, which could reveal sources of potential pressure on the healthcare system should SARS-CoV-2 prevalence increase, and could inform mass vaccination strategies. The aim of this study is to quantify the relationship between COVID-19 patient age and serious outcomes of the disease, beyond fatalities alone.Methods: We analysed 277,555 known SARS-CoV-2 infection records for Ontario, Canada, from 23 January 2020 to 16 February 2021 and estimated the age distributions of hospitalizations, Intensive Care Unit admissions, intubations, and ventilations. We quantified the probability of hospitalization given known SARS-CoV-2 infection, and of survival given COVID-19-related hospitalization.Results: The distribution of hospitalizations peaks with a wide plateau covering ages 60-90, whereas deaths are concentrated in ages 80+. The estimated probability of hospitalization given known infection reaches a maximum of 27.8% at age 80 (95% CI 26.0%-29.7%). The probability of survival given hospitalization is nearly 100% for adults younger than 40, but declines substantially after this age; for example, a hospitalized 54-year-old patient has a 91.7% chance of surviving COVID-19 (95% CI 88.3%-94.4%).Conclusions: Our study demonstrates a significant need for hospitalization in middle-aged individuals and young seniors. This need is not captured by the distribution of deaths, which is heavily concentrated in very old ages. The probability of survival given hospitalization for COVID-19 is lower than is generally perceived for patients over 40. If acute care capacity is exceeded due to an increase in COVID-19 prevalence, the distribution of deaths could expand toward younger ages. These results suggest that vaccine programs should aim to prevent infection not only in old seniors, but also in young seniors and middle-aged individuals, to protect them from serious illness and to limit stress on the healthcare system. [ABSTRACT FROM AUTHOR]

PURPOSE: Acute care utilization (ACU), including emergency department (ED) visits or hospital admissions, is common in patients with cancer and may be preventable. The Center for Medicare & Medicaid Services recently implemented OP-35, a measure in the Hospital Outpatient Quality Reporting Program focused on ED visits and inpatient admissions for 10 potentially preventable conditions that arise within 30 days of chemotherapy. This new measure exemplifies a growing focus on preventing unnecessary ACU. However, identifying patients at high risk of ACU remains a challenge. We developed a real-time clinical prediction model using a discrete point allocation system to assess risk for ACU in patients with active cancer. METHODS: We performed a retrospective cohort analysis of patients with active cancer from a large urban academic medical center. The primary outcome, ACU, was evaluated using a multivariate logistic regression model with backward variable selection. We used estimates from the multivariate logistic model to construct a risk index using a discrete point allocation system. RESULTS: Eight thousand two hundred forty-six patients were included in the analysis. ED utilization in the last 90 days, history of chronic obstructive pulmonary disease, congestive heart failure or renal failure, and low hemoglobin and low neutrophil count significantly increased risk for ACU. The model produced an overall C-statistic of 0.726. Patients defined as high risk (achieving a score of 2 or higher on the risk index) represented 10% of total patients and 46% of ACU. CONCLUSION: We developed an oncology acute care risk prediction model using a risk index–based scoring system, the REDUCE (Reducing ED Utilization in the Cancer Experience) score. Further efforts to evaluate the effectiveness of our model in predicting ACU are ongoing. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity.Methods: In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg-1 min-1 and peak oxygen consumption (VO2 peak) >16 ml kg-1 min-1, cut-points that represent a reduced risk of postoperative complications.Results: Five questions were identified to have dominance in predicting AT>11 ml kg-1 min-1 and VO2 peak>16 ml.kg-1min-1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg-1.min-1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg-1.min-1 and VO2 peak<16 ml.kg-1.min-1.Conclusions: The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management. [ABSTRACT FROM AUTHOR]

Background: In the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients. Methods: The authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune‐related adverse event (irAE) requiring the discontinuation of ICI rechallenge. Best overall response and time to all‐cause death were compared between the patients who did and those who did not undergo ICI rechallenge. Grading was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Results: Of the 102 patients with melanoma who developed high‐grade ICI hepatitis, 31 underwent ICI rechallenge. Although 15 of 31 patients (48%) developed an irAE of any grade, only 6 patients (19%) required ICI discontinuation due to irAE severity (4 of 29 patients [14%] rechallenged with anti–PD‐1 or anti‐PD‐L1 and 2 of 2 patients [100%] rechallenged with ipilimumab). Recurrent hepatitis accounted for 4 of these 6 cases. Rechallenged patients who did not require ICI discontinuation were found to be significantly less likely to receive ipilimumab rather than anti–PD‐1 or anti‐PD‐L1 monotherapy (0% vs 33%; relative risk (RR), 0.1 [95% CI, 0.1‐0.3; P =.032]) and significantly less likely to be rechallenged with their original ICI (8% vs 50%; RR, 0.2 [95% CI, 0.1‐0.7; P =.038]). There was no difference noted with regard to best overall response or time to death between rechallenged and non‐rechallenged patients. Conclusions: ICI therapy can be resumed in patients with melanoma who have recovered from grade 3 to 4 ICI hepatitis with a modest risk of serious irAEs. It remains unclear whether ICI retreatment improves clinical outcomes. After resolution of high‐grade immune‐mediated hepatitis, the majority of patients who are rechallenged with immune checkpoint inhibitors can remain on treatment without developing serious immune‐related adverse events. It remains unclear whether immune checkpoint inhibitor retreatment improves clinical outcomes. [ABSTRACT FROM AUTHOR]

We assessed whether disclosure of HIV status is significantly associated with reported HIV sexual risk behaviors among HIV positive Black/African American men who have sex with men (MSM) (Black MSM) in six cities in the USA. Participants from the BROTHERS (HIV Prevention Trials Network [HPTN 061]) study focused on assessing the feasibility and acceptability of a multifaceted HIV prevention intervention to reduce HIV infections among Black MSM enrolled between July 2009 and October 2010. All participants completed a behavioral assessment using an audio computer-assisted self-interview that included questions about HIV status disclosure, HIV sexual risk behaviors, and other behaviors. Biological samples were also collected. This analysis focused on baseline data of HIV-positive Black MSM in the HPTN 061 study. Of the 143 HIV-positive Black MSM (majority ≥ 35 years of age) included in this analysis, 58% reported disclosing their HIV status to their last male anal sex partner. Forty-three percent and 42% reported condomless insertive and receptive anal intercourse respectively with their last male partner; whereas, 17% and 18% of the sample engaged in condomless insertive and receptive anal intercourse with a serodiscordant/unknown status partner, respectively. In multivariable logistic regression models, there was no statistically significant association between HIV status disclosure and condomless insertive anal intercourse (aOR = 0.35, 95% CI 0.11, 1.08; p = 0.30), condomless receptive anal intercourse (aOR = 2.48, 95% CI 0.94, 6.52; p = 0.20), or condomless receptive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.55, 95% CI 0.20, 1.49; p = 0.45). However, HIV status disclosure was significantly associated with lower odds of reporting condomless insertive anal intercourse with a serodiscordant/unknown status partner (aOR = 0.19, 95% CI 0.06, 0.68; p ≤ 0.01). Among this multi-city sample of HIV-positive Black MSM, disclosure of HIV status was common and associated with lower HIV sexual risk behaviors. These findings should motivate and guide research to develop prevention messages to increase HIV status disclosures. [ABSTRACT FROM AUTHOR]

We formulate the problem of matrix completion with and without side information as a non-convex optimization problem. We design fastImpute based on non-convex gradient descent and show it converges to a global minimum that is guaranteed to recover closely the underlying matrix while it scales to matrices of sizes beyond 105 × 105 . We report experiments on both synthetic and real-world datasets that show fastImpute is competitive in both the accuracy of the matrix recovered and the time needed across all cases. Furthermore, when a high number of entries are missing, fastImpute is over 75% lower in MAPE and 15 times faster than current state-of-the-art matrix completion methods in both the case with side information and without. [ABSTRACT FROM AUTHOR]

In this article, we present a new method based on extreme learning machine (ELM) algorithm for solving nonlinear curve fitting problems. Curve fitting is a computational problem in which we seek an underlying target function with a set of data points given. We proposed that the unknown target function is realized by an ELM with introducing an additional linear neuron to correct the localized behavior caused by Gaussian type neurons. The number of hidden layer neurons of ELM is a crucial factor to achieve a good performance. An evolutionary computation algorithm–particle swarm optimization (PSO) technique is applied to determine the optimal number of hidden nodes. Several numerical experiments with benchmark datasets, simulated spectral data and measured data from high energy physics experiments have been conducted to test the proposed method. Accurate fitting has been accomplished for various tough curve fitting tasks. Comparing with the results of other methods, the proposed method outperforms the traditional numerical-based technique. This work clearly demonstrates that the classical numerical analysis problem-curve fitting can be satisfactorily resolved via the approach of artificial intelligence. [ABSTRACT FROM AUTHOR]

Introduction: New financial incentives, such as reduced Medicare reimbursements, have led hospitals to closely monitor their readmission rates and initiate efforts aimed at reducing them. In this context, many surgical departments participate in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which collects detailed demographic, laboratory, clinical, procedure and perioperative occurrence data. The availability of such data enables the development of data science methods which predict readmissions and, as done in this paper, offer specific recommendations aimed at preventing readmissions. Materials and methods: This study leverages NSQIP data for 722,101 surgeries to develop predictive and prescriptive models, predicting readmissions and offering real-time, personalized treatment recommendations for surgical patients during their hospital stay, aimed at reducing the risk of a 30-day readmission. We applied a variety of classification methods to predict 30-day readmissions and developed two prescriptive methods to recommend pre-operative blood transfusions to increase the patient's hematocrit with the objective of preventing readmissions. The effect of these interventions was evaluated using several predictive models. Results: Predictions of 30-day readmissions based on the entire collection of NSQIP variables achieve an out-of-sample accuracy of 87% (Area Under the Curve—AUC). Predictions based only on pre-operative variables have an accuracy of 74% AUC, out-of-sample. Personalized interventions, in the form of pre-operative blood transfusions identified by the prescriptive methods, reduce readmissions by 12%, on average, for patients considered as candidates for pre-operative transfusion (pre-operative hematoctic <30). The prediction accuracy of the proposed models exceeds results in the literature. Conclusions: This study is among the first to develop a methodology for making specific, data-driven, personalized treatment recommendations to reduce the 30-day readmission rate. The reported predicted reduction in readmissions can lead to more than $20 million in savings in the U.S. annually. [ABSTRACT FROM AUTHOR]

Background: In March of 2013, the Los Angeles County (LAC) Division of HIV and STD Programs implemented a clinic-based Medical Care Coordination (MCC) Program to increase viral suppression (VS) (,200 c/mL) among people living with HIV (PLWH) at high risk for poor health outcomes. Objective: This study aimed to estimate trajectories of VS and to assess whether these trajectories differed by stimulant use, housing instability, and depressive symptom severity as reported by PLWH participating in MCC. Methods: Data represent 6408 PLWH in LAC receiving services from the MCC Program and were obtained from LAC HIV surveillance data matched to behavioral assessments obtained across 35 Ryan White Program clinics participating in MCC. Piecewise mixed-effects logistic regression with a random intercept estimated probabilities of VS from 12 months before MCC enrollment through 36 months after enrollment, accounting for time by covariate interactions for 3 comorbid conditions: housing instability, stimulant use, and depressive symptoms. Results: The overall probability of VS increased from 0.35 to 0.77 within the first 6 months in the MCC Program, and this probability was maintained up to 36 months after enrollment. Those who reported housing instability, stimulant use, or multiple comorbid conditions did not achieve the same probability of VS by 36 months as those with none of those comorbidities. Conclusions: Findings suggest that MCC improved the probability of VS for all patient groups regardless of the presence of comorbidities. However, those with comorbid conditions will still require increased support from patient-centered programs to address disparities in VS. [ABSTRACT FROM AUTHOR]

I B ... [S]tates previously subject to preclearance [under the Voting Rights Act] have purged voters from their electoral rolls at a rate 40 percent higher than other states. b i Nearly one in four eligible Americans is not registered to vote.[28] Many others have out-of-date registrations because they have moved and have not updated their registrations - a process that in states like Texas puts the onus on a voter to complete and then mail in a paper form. This system of voter registration, which has proven remarkably successful, is now used in sixteen states plus the District of Columbia.[30] In Oregon, registration rates quadrupled at DMV offices.[31] In Vermont, registrations jumped 62 percent in the first six months after AVR was put in place.[32] And the benefits have not just been in increased registrations. H.R. 1, already passed by the U.S. House, would do this by requiring that states offer at least two weeks of no excuse early voting and equitably distribute early voting sites.[40]. [Extracted from the article]

• Our study examined differences in experiences of homophobic victimization in men. • Pro-inflammatory genes were upregulated in men who experienced homophobia. • Type I Interferon genes were downregulated in men who experienced homophobia. • Black men had enhanced gene expression alterations compared to Latino men. Men who have sex with men (MSM) experience high rates of homophobic victimization, which is linked to myriad chronic physical and mental health disparities. Social adversity such as rejection, isolation, and racial discrimination can induce a conserved transcriptional response to adversity (CTRA) involving upregulation of proinflammatory genes and downregulation of type I interferon and antibody synthesis genes. This study specifically examines whether homophobic victimization is associated with expression of CTRA profiles in Black and Latino MSM living in Los Angeles. Analyses linked behavioral survey data with quantified RNA from leukocytes from blood samples of 70 participants over 12 months. CTRA gene expression was increased by 3.1-fold in MSM who experienced homophobic victimization while adjusting for major leukocyte subsets and sociodemographics. Accounting for all these factors, CTRA gene expression was significantly enhanced in MSM who identified as Black compared to Latino. Our findings identify experiences of homophobic victimization as drivers of inflammatory and type I interferon gene expression profiles, which can contribute to physical and mental health challenges in Black and Latino MSM. [ABSTRACT FROM AUTHOR]

• First-principles molecular dynamics simulations show that pressure causes thioaldehydes to oligomerize and to bind with surfaces of MgO. • Reactions are reversible for loads below 18 GPa. • At higher pressure, the irreversible formation of C O bonds between the MgO surface and the oligomers irreversibly damages the surface. • The results suggest that developing lubricants that avoid the formation of C O bonds with oxide surfaces is important for high pressure applications. First-principles molecular dynamics (FPMD) simulations are used to investigate the chemical response of thioaldehyde (MeCHS) to compression between (001) surfaces of magnesium oxide (MgO), with the external load reaching values as high as 20 GPa. The results demonstrate that the application of a load transforms the MeCHS molecules into oligomers through the formation of C S, S S, and C C bonds between MeCHS monomers and through proton transfer. The application of a load facilitates the reactions by decreasing the distance between the reacting molecules. The oligomers bonded to the MgO surface through the formation of C O and S O bonds, involving an oxygen atom in the surface. Proton transfer between the oligomers and the surface was also observed. No reactions were observed to take place between the oligomers and the magnesium atoms. The formation of bonds with the oxygen atoms in the surface led to an increase in the Mg O distances within the surfaces, and thus a large disruption of the surface structure. The changes in structure were found to be reversible until 18 GPa, suggesting that the MeCHS oligomers may be effective at inhibiting wear by preventing direct surface-surface contacts without introducing new sources of irreversible changes in the surface structure for a certain range of loads (until 18 GPa). As a whole, the study describes in detail the chemical behavior of MeCHS in response to compression between MgO surfaces. This information could be applied to other molecules containing sulfinyl chemical groups and other metal oxides surfaces. Image, graphical abstract [ABSTRACT FROM AUTHOR]

There is growing evidence that cardiac dysfunction in patients with chronic epilepsy could play a pathogenic role in sudden unexpected death in epilepsy (SUDEP). Recent animal studies have revealed that epilepsy secondarily alters the expression of cardiac ion channels alongside abnormal cardiac electrophysiology and remodeling. These molecular findings represent novel evidence for an acquired cardiac channelopathy in epilepsy, distinct from inherited ion channels mutations associated with cardiocerebral phenotypes. Specifically, seizure activity has been shown to alter the messenger RNA (mRNA) and protein expression of voltage‐gated sodium channels (Nav1.1, Nav1.5), voltage‐gated potassium channels (Kv4.2, Kv4.3), sodium‐calcium exchangers (NCX1), and nonspecific cation‐conducting channels (HCN2, HCN4). The pathophysiology may involve autonomic dysfunction and structural cardiac disease, as both are independently associated with epilepsy and ion channel dysregulation. Indeed, in vivo and in vitro studies of cardiac pathology reveal a complex network of signaling pathways and transcription factors regulating ion channel expression in the setting of sympathetic overactivity, cardiac failure, and hypertrophy. Other mechanisms such as circulating inflammatory mediators or exogenous effects of antiepileptic medications lack evidence. Moreover, an acquired cardiac channelopathy may underlie the electrophysiologic cardiac abnormalities seen in chronic epilepsy, potentially contributing to the increased risk of malignant arrhythmias and sudden death. Therefore, further investigation is necessary to establish whether cardiac ion channel dysregulation similarly occurs in patients with epilepsy, and to characterize any pathogenic relationship with SUDEP. [ABSTRACT FROM AUTHOR]

Two linear ([sup 1]Σ[sup +] and [sup 1]Π) and three bent (1 [sup 1]A[sup ′], 2 [sup 1]A[sup ′], and 1 [sup 1]A[sup ″]) lowest-lying electronic singlet states of AlOH have been systematically investigated employing ab initio self-consistent-field, configuration interaction with single and double excitations, coupled cluster with single and double excitations (CCSD), CCSD with perturbative triple excitations [CCSD(T)], and CCSD with iterative partial triple excitations (CCSDT-3 and CC3) quantum mechanical methods with basis sets up to augmented correlation consistent polarized valence quadruple zeta (aug-cc-pVQZ). The linear [sup 1]Σ[sup +] state is found to be a remarkably low-energy transition state between the two equivalent bent 1 [sup 1]A[sup ′] structures, while the linear [sup 1]Π state is a second-order saddle point, which leads to the bent 2 [sup 1]A[sup ′] and 1 [sup 1]A[sup ″] states. The bent ground (X [sup 1]A[sup ′]) state of AlOH is predicted to have a bond angle of 157° at the aug-cc-pVQZ CC3 level of theory and is classified as a quasilinear molecule, confirming previous studies. Employing the equation-of-motion coupled cluster method, the first singlet excited state (à [sup 1]A[sup ′]) is predicted to have a bond angle of 110° and to lie 114 kcal/mol (39 900 cm-1, 4.94 eV) above the ground state, whereas the second singlet excited state (B [sup 1]A[sup ″]) is predicted to have a bond angle of 116° and to be located 119 kcal/mol (41 700 cm-1, 5.17 eV) above the ground state. These theoretical energy separations are in excellent agreement with the experimental values T[sub 0] (à [sup 1]A[sup ′])=114.57 kcal/mol (40 073 cm[sup -1], 4.968 eV) and T[sub 0] (B [sup 1]A[sup ″])=119.36 kcal/mol (41 747 cm[sup -1], 5.176 eV). The barriers to linearity for the two bent singlet excited states are determined to be 11.6 kcal/mol for the à [sup 1]A[sup ′] state and 6.2 kcal/mol for the B [sup 1]A[sup ″] state. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Fires in buildings are significant public safety hazards and can result in fatalities and substantial financial losses. Studies have shown that the socioeconomic makeup of a region can impact the occurrence of building fires. However, existing models based on the classical stepwise regression procedure have limitations. This paper proposes a more accurate predictive model of building fire rates using a set of socioeconomic variables. To improve the model's forecasting ability, a backward elimination by robust final predictor error (RFPE) criterion is introduced. The proposed approach is applied to census and fire incident data from the South East Queensland region of Australia. A cross-validation procedure is used to assess the model's accuracy, and comparative analyses are conducted using other elimination criteria such as p-value, Akaike's information criterion (AIC), Bayesian information criterion (BIC), and predicted residual error sum of squares (PRESS). The results demonstrate that the RFPE criterion is a more accurate predictive model based on several goodness-of-fit measures. Overall, the RFPE equation was found to be a suitable criterion for the backward elimination procedure in the socioeconomic modeling of building fires. [ABSTRACT FROM AUTHOR]

In this paper, we derive and analyze a state-structured epidemic model for infectious diseases in which the state structure is nonlocal. The state is a measure of infectivity of infected individuals or the intensity of viral replications in infected cells. The model gives rise to a system of nonlinear integro-differential equations with a nonlocal term. We establish the well-posedness and dissipativity of the associated nonlinear semigroup. We establish an equivalent principal spectral condition between the linearized operator and the next-generation operator and show that the basic reproduction number R 0 is a sharp threshold: if R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, and if R 0 > 1 , the disease-free equilibrium is unstable and a unique endemic equilibrium is globally asymptotically stable. The proof of global stability of the endemic equilibrium utilizes a global Lyapunov function whose construction was motivated by the graph-theoretic method for coupled systems on networks developed in [24] . [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men with histories of homophobic victimization bear heightened risk of unstable housing and methamphetamine use. However, it is unclear whether unstable housing explains the link between homophobic victimization and methamphetamine use in this group. The present study aims to test associations between homophobic victimization, unstable housing, and recent methamphetamine use across 24 months in a cohort of men of color who have sex with men (MoCSM).Methods: Our analysis stems from data of 1342 person-visits from 401 MoCSM participating in an ongoing cohort study. We performed a lagged multilevel negative binominal regression to test the association between past homophobic victimization and recent unstable housing, and a lagged multilevel ordered logistic regression to test the association between past homophobic victimization recent methamphetamine use. We then performed a path analysis to test whether recent unstable housing mediates the association between past homophobic victimization and recent methamphetamine use.Results: Findings showed homophobic victimization associated significantly with increased odds of unstable housing (IRR = 1.70, 95% CI [1.35, 2.14], p < 0.001) and recent methamphetamine use (OR = 1.40, 95% CI [1.15, 1.71], p = 0.001). Mediation analysis indicated that past homophobic victimization was indirectly associated with recent methamphetamine use via unstable housing (OR = 1.06 (95% CI [1.01, 1.11], p = 0.010).Conclusion: Our findings suggest that homophobic victimization and unstable housing should be addressed alongside treatment and prevention of methamphetamine use in MoCSM. [ABSTRACT FROM AUTHOR]

Twenty years after publication of the report To Err Is Human, studies demonstrate persisting high levels of patient harm. Most patient safety measurement remains highly retrospective, relying on voluntary reporting and post discharge administrative coding. Progress has been limited by the lack of advances in measurement accuracy, detection sensitivity, and timely actionability. The broad adoption of electronic health records (EHRs) offers a significant opportunity to leverage digital information to improve safety measurement and management using real-time data. We developed a novel method to extract safety indicators from EHRs to identify harm and its precursors by implementing a patient safety active management system (PSAM) in hospitals within a national Patient Safety Organization (PSO). The PSAM generated validated adverse event outcomes and leveraged EHR data to develop a real-time safety predictive model. This study describes the PSAM's pilot at two large community hospitals in 2014-17. We found that the PSAM could detect harm in real time, at higher rates than current levels are detected, and that such harm could be predicted. In addition to outlining future opportunities and challenges with this EHR-enabled PSAM approach, we discuss implications and next steps for policy and practice. [ABSTRACT FROM AUTHOR]

Purpose: The Duke Activity Status Index (DASI), a patient-administered questionnaire, is used to quantify functional capacity in patients undergoing cancer surgery.Methods: This retrospective cohort study assessed whether the DASI was accurate in predicting peak oxygen consumption (pVO2) that was objectively measured using cardiopulmonary exercise testing (CPET) in 43 consecutive patients scheduled for elective major cancer surgery at a tertiary cancer centre. The primary outcome measured the limits of agreement between DASI-predicted pVO2 and actual measured pVO2.Results: The study population was elderly (median 63 years, interquartile range 18), 58% were male, with the majority having intraabdominal cancer surgery. Although the DASI scores were statistically related to the measured pVO2 (N = 43, adjusted R2 = 0.20, p = 0.002), both the bias (8 ml kg− 1 min− 1) and 95% limits of agreement (19.5 to − 3.4 ml kg− 1 min− 1) between the predicted and measured pVO2 were large. Using some of the individual components, recalibrating the intercept and regression coefficient of the total DASI score did not substantially improve its ability to predict the measured pVO2.Conclusion: In summary, both the limits of agreement and bias between the measured and DASI-predicted pVO2 were substantial. The DASI-predicted pVO2 based on patient’s assessment of their functional status could not be considered a reliable surrogate of measured pVO2 during CPET for the population of patients pending major cancer surgery and cannot, therefore, be used as a triage tool for referral to CPET centres for objective risk assessment. [ABSTRACT FROM AUTHOR]

Introduction: Technological solutions for quantifying Parkinson's disease (PD) symptoms may provide an objective means to track response to treatment, including side effects such as levodopa-induced dyskinesia. Vision-based systems are advantageous as they do not require physical contact with the body and have minimal instrumentation compared to wearables. We have developed a vision-based system to quantify a change in dyskinesia as reported by patients using 2D videos of clinical assessments during acute levodopa infusions.Methods: Nine participants with PD completed a total of 16 levodopa infusions, where they were asked to report important changes in dyskinesia (i.e. onset and remission). Participants were simultaneously rated using the UDysRS Part III (from video recordings analyzed post-hoc). Body joint positions and movements were tracked using a state-of-the-art deep learning pose estimation algorithm applied to the videos. 416 features (e.g. kinematics, frequency distribution) were extracted to characterize movements. The sensitivity and specificity of each feature to patient-reported changes in dyskinesia severity was computed and compared with physician-rated results.Results: Features achieved similar or superior performance to the UDysRS for detecting the onset and remission of dyskinesia. The best AUC for detecting onset of dyskinesia was 0.822 and for remission of dyskinesia was 0.958, compared to 0.826 and 0.802 for the UDysRS.Conclusions: Video-based features may provide an objective means of quantifying the severity of levodopa-induced dyskinesia, and have responsiveness as good or better than the clinically-rated UDysRS. The results demonstrate encouraging evidence for future integration of video-based technology into clinical research and eventually clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cathepsin S ( CatS) and proteinase - activated receptor ( PAR)- 2 are involved in the remodelling of vascular walls and neointima formation as well as in alloantigen presentation and T-cell priming. Therefore, we hypothesized that CatS/PAR-2 inhibition/deficiency would attenuate chronic allograft vasculopathy. Methods: Heterotopic aortic murine transplantation was performed from 657BL/ 63 donors to £ 57BL/ 6J re- cipients (syngeneic control group), Balb/c to 657BL/6J without treatment (allogenic control group), Balb/c to 657BL/ 63 with twice daily oral CatS inhibitor (allogenic treatment group ) and Balb/ c to Parl-/- C57BL/6J (allogenic knockout group). The recipients were sacrificed on day 28 and the grafts were harvested for histological analysis and RT-qPCR. Results: After 28 days, mice of the allogenic control group exhibited significant neointima formation and massive CD8 T-cell infiltration into the neointima while the syngeneic control group showed negligible allograft vasculopathy. The mRNA expression level of CatS in allografts was 5-fold of those in syngeneic grafts. Neointima formation and therefore intima/media-ratio were significantly decreased in the treatment and knockout group in comparison to the allogenic control group. Mice in treatment group also displayed significantly fewer CD8 T cells in the neointima compared with allogeneic controls. Additionally, treatment with the CatS inhibitor and PAR2- deficiency decreased mRNA-levels of interleukins and cytokines. Conclusion: In conclusion. our data indicate that inhibiting CatS and PAR-2 deficiency led to a marked reduction of neointima formation and associated inflammation in a murine heterotopic model for allograft vasculopathy. [ABSTRACT FROM AUTHOR]

Background: Time to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally. Methods: A Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463. Results: Twenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24–240 days), and patient delay (20 days–2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment. Conclusion: Time to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups. Trial registration N/a. [ABSTRACT FROM AUTHOR]

Simple Summary: Young survivors of bone tumors and soft-tissue sarcoma are at risk of cognitive impairment due to their previous cancer therapies and the development of cancer-/treatment-related chronic health conditions as they age. We postulate that a compromised health status, coupled with the continued engagement in an unhealthy lifestyle during survivorship, may further exacerbate cognitive impairment among survivors. Our study found that survivors of bone tumors and soft-tissue sarcoma demonstrated impairment in attention, processing speed and executive function (higher order thinking ability). Low physical activity and smoking were associated with inattention. Survivors who worked >9 h per day had worse executive function than those with shorter working hours. Of note is that survivors who had a chronic health condition and were physically inactive demonstrated the worst attention and executive function performance. Our findings support continual efforts to investigate intervention targets and leverage health behaviors as modifiable risk factors to prevent cognitive dysfunction in this population. Background: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15–39 years) of sarcoma. Methods: This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables. Results: At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3–13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = −0.97, p = 0.003) and sleep-related fatigue (estimate = −0.08, p = 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42, p = 0.023) and cognitive flexibility (estimate = 5.22, p = 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs*physical activity) showed that survivors who developed CHCs and reported low physical activity had worse attention (p = 0.032) and cognitive-flexibility (p = 0.019) scores than other subgroups. Conclusion: Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures. [ABSTRACT FROM AUTHOR]

Simple mechanistic epidemic models are widely used for forecasting and parameter estimation of infectious diseases based on noisy case reporting data. Despite the widespread application of models to emerging infectious diseases, we know little about the comparative performance of standard computational-statistical frameworks in these contexts. Here we build a simple stochastic, discrete-time, discrete-state epidemic model with both process and observation error and use it to characterize the effectiveness of different flavours of Bayesian Markov chain Monte Carlo (MCMC) techniques. We use fits to simulated data, where parameters (and future behaviour) are known, to explore the limitations of different platforms and quantify parameter estimation accuracy, forecasting accuracy, and computational efficiency across combinations of modeling decisions (e.g. discrete vs. continuous latent states, levels of stochasticity) and computational platforms (JAGS, NIMBLE, Stan). [ABSTRACT FROM AUTHOR]

Summary: Objectives: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug‐resistant epilepsy, its safety, and the factors influencing individual outcomes. Methods: A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug‐resistant epilepsy. Reference lists of these articles were used to source further articles. Results: Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%‐90% seizure reduction with ANT‐DBS, and a 48%‐95% seizure reduction with HC‐DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three‐fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders—experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox‐Gastaut syndrome. Significance: We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large‐scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response. [ABSTRACT FROM AUTHOR]

African-American men who have sex with men and women (MSMW) are among those most heavily impacted by HIV in the United States, and those who have histories of incarceration are at further risk of infection. The Men in Life Environments (MILE) HIV prevention intervention was developed to provide culturally appropriate skills-based education and support for African-American MSMW with recent histories of incarceration. The MILE's conceptual framework was informed by three theories: Theory of Reasoned Action and Planned Behavior, Critical Thinking and Cultural Affirmation Model, and Empowerment Theory. The theory-based framework posits that improving racial pride is crucial in building self-efficacy and intentions that in turn promote health-protective behaviors. Therefore, our study aimed to assess whether baseline associations between racial pride and condom use self-efficacy, intentions, and behaviors among African-American MSMW with histories of incarceration align with our conceptual model. We report data on 212 participants recruited from Los Angeles County Sheriff's Department Men's Central Jail and the local community. Using structural equation modeling, we tested two separate models: one with female sexual partners and one with male sexual partners, while stratifying by participant's HIV status. Only among HIV-negative participants was greater racial pride associated with less condomless intercourse with men. In this group, greater self-efficacy and intentions-but not racial pride-predicted less condomless intercourse with women. Our findings suggest that racial pride is an important factor to address in HIV prevention interventions for post-incarcerated African-American MSMW. [ABSTRACT FROM AUTHOR]

Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain. Based on previous reports quantifying total viral DNA levels in brain from HIV-1 and SIV infections, estimates of integrated proviral DNA burden were made, which were used to calibrate the mathematical model predicting viral accrual in brain macrophages from primary infection. The annual rate at which susceptible brain macrophages become HIV-1 infected was estimated to be 2.90×10-4.87×10 per year for cART-treated HIV/AIDS patients without comorbid neurological disorders. The transmission rate for SIV infection among untreated macaques was estimated to be 5.30×10-1.37×10 per year. An improvement in cART effectiveness (1.6-48%) would suppress HIV-1 infection in patients without neurological disorders. Among patients with advanced disease, a substantial improvement in cART effectiveness (70%) would eradicate HIV-1 provirus from the brain within 3-32 (interquartile range 3-9) years in patients without neurological disorders, whereas 4-51 (interquartile range 4-16) years of efficacious cART would be required for HIV/AIDS patients with comorbid neurological disorders. HIV-1 and SIV provirus burdens in the brain increase over time. A moderately efficacious antiretroviral therapy regimen could eradicate HIV-1 infection in the brain that was dependent on brain macrophage lifespan and the presence of neurological comorbidity. [ABSTRACT FROM AUTHOR]

Objective The present paper describes our experience of developing and piloting a best practice model of medical clinical handover. Secondary aims were to improve reliability of communication, identify negative effects on patient care and assess staff adherence and acceptance of the process. Methods We described existing handover practice. We designed and implemented a process incorporating bedside handover, the Identification, Situation, Background, Assessment, Requirements and Requests ( ISBAR) tool and handover documentation. We audited the process and surveyed doctors before and after the intervention regarding their practice and preferences. Results Existing handover practice was remote from the patient, neither standardised nor documented. The new process resulted in a median 87% (95% CI 70.4-92.1) of handovers in the presence of the patient. ISBAR elements were consistently communicated, median 100% (95% CI 91.8-100). Risk events were directly identified in a median 8.3% (95% CI 0.0-13.8) of bedside handovers. Handover documentation did not improve. FACEM and registrar perception that bedside handover improves patient care fell from 71%, 80% to 56%, 58%, respectively. Preference for bedside handover fell from 79% and 80%, respectively, to being evenly divided between bedside and centralised models; 80.9% of respondents reported that ISBAR improved communication. Conclusion Bedside handover using ISBAR resulted in improved patient involvement, communication and a non-significant trend to improved patient safety. Despite a majority of doctors acknowledging these findings, preference remained for a centralised handover using ISBAR. Gaining staff acceptance of a process change is essential to its success. A barrier to acceptance could be that staff are time-poor. We suggest handover processes can be strengthened by adequate staffing and small, incremental improvements to existing models combined with auditing of outcomes. [ABSTRACT FROM AUTHOR]

Background: WHO and UNAIDS prioritized 14 eastern and southern African countries with high HIV and low male circumcision prevalence for a voluntary medical male circumcision (VMMC) scale-up in 2007. Because circumcision provides only partial protection against HIV infection to men, the issue of possible risk compensation in response to VMMC campaigns is of particular concern. In this study, we looked at population-level survey data from the countries prioritized by WHO for a VMMC scale-up. We compared the difference in sexual risk behaviours (SRB) between circumcised and uncircumcised men before and after the WHO’s official VMMC promotion. Materials and methods: Ten countries (Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe) participating in the WHO’s VMMC scale-up had available data from the Demographic and Health Surveys (DHS). We used cumulative-link mixed models to investigate interactions between survey period and circumcision status in predicting SRB, in order to evaluate whether the difference between the behavior of the two groups changed before and after the scale-up, while controlling for socio-demographic and knowledge-related covariates. The main responses were condom use at last sex and number of non-cohabiting sexual partners, both in the last 12 months. Results: There was little change in condom use by circumcised men relative to uncircumcised men from before the VMMC scale up to after the scale up. The relative odds ratio is 1.06 (95% CI, 0.95–1.18; interaction P = 0.310). Similarly, there was little change in the number of non-cohabiting partners in circumcised men (relative to uncircumcised men): the relative odds ratio of increasing the number of partners is 0.95 (95% CI, 0.86–1.05; interaction P = 0.319). Age, religion, education, job, marital status, media use and HIV knowledge also showed statistically significant association with the studied risk behaviours. We also found significant differences among countries, while controlling for covariates. Conclusions: Overall, we find no evidence of sexual risk compensation in response to VMMC campaigns in countries prioritized by WHO. Changes in relative partner behaviour and the relative odds of condom use were small (and of uncertain sign). In fact, our estimates, though not significant, both suggest slightly less risky behavior. We conclude that sexual risk compensation in response to VMMC campaigns has not been a serious problem to date, but urge continued attention to local context, and to promulgating accurate messages about circumcision within and beyond the VMMC context. [ABSTRACT FROM AUTHOR]