Search

The ProteinPaint Hi-C tool (ppHiC) facilitates web-based visualization and collaborative exploration of Hi-C data, a vital resource for understanding three-dimensional genomic structures. ppHiC allows researchers to easily analyze large Hi-C datasets on a web browser without requiring the computational expertise that has heretofore limited access to this complex genomic data. The platform is compatible with multiple Hi-C data versions and boasts a highly customizable interface, including a configuration panel for the precise adjustment of key visualization parameters. The tool's interactive features offer a broad range of views, from whole-genome landscapes to detailed interactions between pairs of loci, that are accessible within a single, integrated environment. Here, we demonstrate how using ppHiC to visualize an altered chromatin conformational landscape in neuroblastoma can inform understanding of the genomic rearrangements in this cancer., Competing Interests: Authors declare no competing interest., (© 2024 The Authors.)

The fluid movement of an arm requires multiple spatiotemporal parameters to be set independently. Recent studies have argued that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independent components of the neural dynamics. Using a task where three male monkeys made a sequence of reaching movements to randomly placed targets, we show that the spatial and temporal parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity in motor cortex: each movement's direction corresponds to a fixed neural trajectory through neural state space and its speed to how quickly that trajectory is traversed. Recurrent neural network models show that this coding allows independent control over the spatial and temporal parameters of movement by separate network parameters. Our results support a key prediction of the dynamical systems view of motor cortex, and also argue that not all parameters of movement are defined by different trajectories of population activity., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Colins Rodriguez et al.)

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, social determinants of health, health outcomes, and loneliness. Antiretroviral therapy (ART) adherence was assessed electronically with the medication event monitoring system. Bivariate linear regressions analysis showed higher loneliness scores among those with higher levels of internalized HIV stigma, depression, unmet needs, and discrimination related to HIV serostatus, race, and sexual orientation. In addition, participants who were married or living with a partner, had stable housing, and reported receiving more social support had lower levels of loneliness. In multivariable regression models controlling for correlates of loneliness, loneliness was found to be a significant independent predictor of worse general physical health, worse general mental health, and greater depression. Loneliness was marginally associated with lower ART adherence. Findings suggest that Black adults living with HIV, who experience multiple intersectional stigmas, require targeted interventions and resources., (© 2023. The Author(s).)

Objectives: Black Americans have been disproportionally affected by the HIV epidemic, and experience significant disparities in sleep health, mental health, and physical health domains. Using longitudinal data from a sample of Black adults with HIV, the current study examined the associations between stigma and mental and physical health outcomes and how sleep disturbance may play a mediating role., Methods: Data were drawn from a recent randomized controlled trial. Questionnaires were used to examine internalized and anticipated HIV stigma, perceived discrimination (enacted stigma) based on multiple social identities (i.e., HIV-serostatus, race, sexual orientation), sleep disturbance, mental health problems (depressive and posttraumatic stress disorder [PTSD] symptoms), and mental and physical health-related quality of life (HRQOL) at baseline, 7-month follow-up, and 13-month follow-up assessments. Linear mixed modeling was used to examine main effects of stigma on health outcomes; causal mediation analysis was used to estimate indirect paths through sleep disturbance., Results: Internalized and anticipated HIV stigma and multiple discrimination were associated with more sleep disturbance, more depressive and PTSD symptoms, and poorer mental and physical HRQOL. Results also indicated significant indirect paths (i.e., mediation) through greater sleep disturbance between HIV-related stigma and discrimination and mental health and health-related quality of life., Conclusions: Results support that sleep disturbance is a mediating pathway through which different forms of stigmas impact health outcomes. Sleep may be an intervention target to help improve mental and physical well-being and reduce health disparities among racial and ethnic minority people with HIV., (© 2024. The Author(s).)

Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessive-compulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berg, Webler, Klein and Kushner.)

Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses taken, as measured by electronic monitoring in separate analyses) among 92 sexual minority Black Americans living with HIV. Mean adherence was 66.5% in month 8 after baseline (36% ≥ 85% adherence; 49% ≥ 75% adherence). Ritual-centered coping moderated the relationship between each of the three types of discrimination at baseline and good ART adherence in month 8 (regardless of the minimum threshold for good adherence); when use of ritual coping was low, the association between discrimination and adherence was statistically significant. The other three coping scales each moderated the association between racial discrimination and good ART adherence (defined by the 75% threshold); cognitive/emotional debriefing was also a moderator for both HIV- and race-related discrimination at the 85% adherence threshold. These findings support the benefits of Africultural coping, particularly ritual-centered coping, to help sexual minority Black Americans manage stressors associated with discrimination and to adhere well to ART., (© 2023. The Author(s).)

The current study examined the prevalence and typology of unmet needs and the association between unmet needs and HIV antiretroviral therapy (ART) medication adherence among a sample of Black people living with HIV(PLHIV) (N = 304) in Los Angeles, CA. We found a high prevalence of unmet needs, with 32% of participants reporting having two or more unmet needs. The most common unmet needs category was basic benefits needs (35%), followed by subsistence needs (33%), and health needs (27%). Significant correlates of unmet needs included food insecurity, history of homelessness, and history of incarceration. A greater number of unmet needs and any unmet basic benefits needs were each significantly associated with lower odds of HIV ART medication adherence. These findings provide further evidence linking the social determinants of health and social disenfranchisement to ART medication adherence among Black PLHIV., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Enhanced S-cone syndrome (ESCS), also known as Goldmann-Favre syndrome, is a retinal degeneration that presents in childhood and leads to progressive nyctalopia and visual field loss. In advanced cases, this degeneration can result in loss of central visual acuity. We describe the case of a 15-year-old boy with ESCS who presented with retinal detachment, a rare complication., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Objective: Studies have demonstrated that reduced drinking without total abstinence is associated with improved outcomes in outpatients with alcohol use disorder (AUD). We sought to examine this question in AUD inpatients who have comorbid anxiety disorders, a common presentation in AUD., Method: This is a secondary analysis of data from a randomized controlled trial for N = 241 inpatients with AUD and comorbid anxiety disorders. Change from baseline drinking level was measured at 1-, 4-, and 12-months postdischarge, and psychological and functional outcomes were measured at 4- and 12-months postdischarge. Three groups were compared: abstinent, reduced (reduced drinking by 1-3 World Health Organization drinking risk levels without abstinence), or nonreduced (maintained or increased drinking risk level)., Results: At 1-, 4-, and 12-months posttreatment, most patients reported abstinence (83, 63, and 60%), and 11, 25, and 26% reported drinking at a reduced level. Drinking reductions achieved at 1-month posttreatment were maintained at 12-month posttreatment by 74% of participants. Overall, the abstinent group reported the best psychological and functional outcomes at follow-ups, followed by the reduced group. Few differences were observed between reducers and nonreducers, but reducers reported significantly better alcohol dependence severity and alcohol-related problems than nonreducers., Conclusions: Though abstinence was associated with the best outcomes in this abstinence-based treatment sample, we conclude that reduced drinking is also associated with significant improvements in alcohol-related outcomes in inpatients with AUD and comorbid anxiety disorders.At 1-, 4-, and 12-months posttreatment, most patients reported abstinence (83, 63, and 60%), and 11, 25, and 26% reported drinking at a reduced level. Drinking reductions achieved at 1-month posttreatment were maintained at 12-month posttreatment by 74% of participants. Overall, the abstinent group reported the best psychological and functional outcomes at follow-ups, followed by the reduced group. Few differences were observed between reducers and nonreducers, but reducers reported significantly (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A * (Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei 1 . Reflection of X-rays from Sgr A * by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years 2 . The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A * are consistent with the reflection scenario 3-5 . If this interpretation is correct, the reflected continuum emission should be polarized 6 . Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of -48° ± 11°. The polarization angle is consistent with Sgr A * being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A * was briefly comparable to that of a Seyfert galaxy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Summary: ProteinPaint BAM track (ppBAM) is designed to assist variant review for cancer research and clinical genomics. With performant server-side computing and rendering, ppBAM supports on-the-fly variant genotyping of thousands of reads using Smith-Waterman alignment. To better visualize support for complex variants, reads are realigned against the mutated reference sequence using ClustalO. ppBAM also supports the BAM slicing API of the NCI Genomic Data Commons (GDC) portal, letting researchers conveniently examine genomic details of vast amounts of cancer sequencing data and reinterpret variant calls., Availability and Implementation: BAM track examples, tutorial, and GDC file access links are available at https://proteinpaint.stjude.org/bam/. Source code is available at https://github.com/stjude/proteinpaint., (© The Author(s) 2023. Published by Oxford University Press.)

Structural inequities have led to HIV disparities, including relatively low antiretroviral therapy adherence and viral suppression rates among Black Americans living with HIV. We conducted a randomized controlled trial of Rise, a community-based culturally congruent adherence intervention, from January 2018 to December 2021 with 166 (85 intervention, 81 control) Black adults living with HIV in Los Angeles County, California [M (SD) = 49.0 (12.2) years-old; 76% male]. The intervention included one-on-one counseling sessions using basic Motivational Interviewing style to problem solve about adherence, as well as referrals to address unmet needs for social determinants of health (e.g., housing services, food assistance). Assessments included electronically monitored adherence; HIV viral load; and baseline, 7-month follow-up, and 13-month follow-up surveys of sociodemographic characteristics, HIV stigma, medical mistrust, and HIV-serostatus disclosure. Repeated-measures intention-to-treat regressions indicated that Rise led to significantly (two-fold) higher adherence likelihood, lower HIV stigmatizing beliefs, and reduced HIV-related medical mistrust. Effects on HIV viral suppression, internalized stigma, and disclosure were non-significant. Moreover, Rise was cost-effective based on established standards: The estimated cost per person to reach optimal adherence was $335 per 10% increase in adherence. Interventions like Rise, that are culturally tailored to the needs of Black populations, may be optimal for Black Americans living with HIV (ClinicalTrials.gov #NCT03331978)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10 -10 ; 0 and 400: p < 10 -10 ). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis.

Background: Internalizing (anxiety and mood) disorders (INTD) commonly co-occur (are "comorbid") with alcohol use disorder (AUD). The literature suggests that excessive alcohol use aimed at coping with INTD symptoms is, at best, a partial explanation for the high comorbidity rates observed. We hypothesized that individuals with INTD experience greater susceptibility to developing AUD symptoms due to the partially shared neurobiological dysfunctions underlying both conditions. We probe this hypothesis by testing the prediction that, after accounting for the volume of alcohol intake, individuals with INTD experience higher levels of alcohol-related symptoms., Methods: Data from the National Epidemiological Survey on Alcohol-Related Conditions (NESARC) Wave 3 were used for the primary analyses, and NESARC Wave 1 data were used for independent replication analyses. Individuals who reported any alcohol use in the prior year were categorized as: (1) never having had an INTD diagnosis ("INTD-Never"); (2) having a remitted INTD diagnosis only ("INTD-Remitted"); or (3) having current INTD diagnosis ("INTD-Current"). Between-group contrasts of alcohol-related symptoms controlled for total alcohol intake (past year), drinking pattern (e.g., binging) and variables previously shown to mark exaggerated AUD symptoms relative to drinking amount (e.g., SES, gender, and family history)., Results: With all covariates in the model, individuals in the INTD-Current group and the INTD-Remitted group reported significantly greater alcohol-related symptoms than those in the INTD-Never group but did not themselves differ in level of alcohol-related symptoms. These results were replicated in the NESARC 1 dataset., Conclusions: Individuals with INTD experience more alcohol-related symptoms than those who drink at the same level. While considering other explanations, we argue that this "harm paradox" is best explained by the view that INTD confers a neurobiologically mediated susceptibility to the development of AUD symptoms., (© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Pulsar wind nebulae are formed when outflows of relativistic electrons and positrons hit the surrounding supernova remnant or interstellar medium at a shock front. The Vela pulsar wind nebula is powered by a young pulsar (B0833-45, aged 11,000 years) 1 and located inside an extended structure called Vela X, which is itself inside the supernova remnant 2 . Previous X-ray observations revealed two prominent arcs that are bisected by a jet and counter jet 3,4 . Radio maps have shown high linear polarization of 60% in the outer regions of the nebula 5 . Here we report an X-ray observation of the inner part of the nebula, where polarization can exceed 60% at the leading edge-approaching the theoretical limit of what can be produced by synchrotron emission. We infer that, in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Magnetars are neutron stars with ultrastrong magnetic fields, which can be observed in x-rays. Polarization measurements could provide information on their magnetic fields and surface properties. We observed polarized x-rays from the magnetar 4U 0142+61 using the Imaging X-ray Polarimetry Explorer and found a linear polarization degree of 13.5 ± 0.8% averaged over the 2- to 8-kilo-electron volt band. The polarization changes with energy: The degree is 15.0 ± 1.0% at 2 to 4 kilo-electron volts, drops below the instrumental sensitivity ~4 to 5 kilo-electron volts, and rises to 35.2 ± 7.1% at 5.5 to 8 kilo-electron volts. The polarization angle also changes by 90° at ~4 to 5 kilo-electron volts. These results are consistent with a model in which thermal radiation from the magnetar surface is reprocessed by scattering off charged particles in the magnetosphere.

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray-emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray-emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis.

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization-the only range available until now-probe extended regions of the jet containing particles that left the acceleration site days to years earlier 1-3 , and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree Π X of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock., (© 2022. The Author(s).)

Background: Drinking to cope with negative affect confers a direct risk of alcohol problems independently of greater alcohol consumption (i.e., confers susceptibility to the alcohol harm paradox). However, it remains unclear whether this risk is common across gender and countries., Methods: The current study applied path analysis to two cross-sectional samples of 18-25-year-old undergraduate hazardous drinking students recruited from the UK (Study 1; N = 873) and internationally (Study 2; N = 4064 recruited in Argentina, Canada, South Africa, Spain, Uruguay, USA, and England). The Drinking Motives Questionnaire (DMQ) measured drinking to cope with negative affect and drinking to enhance positive affect (i.e., enhancement motives). The Alcohol Use Disorders Identification Test (AUDIT) measured alcohol consumption and problems., Results: In both studies, drinking to cope with negative affect had a direct effect on alcohol problems (S1: β  = 0.259, SE = 0.031, p  <.001; S2: β  = 0.255, SE = 0.017, p  <.001), and only a negligible proportion of this effect was mediated by alcohol consumption (S1: 2.58 %, p  =.550; S2: 0.79 %, p= .538). By contrast, drinking to enhance positive affect had a smaller direct effect on alcohol problems (S1: β  = 0.000, SE = 0.033, p  =.989; S2: β  = 0.044, SE = 0.017, p  =.009), and a substantial proportion of this effect was mediated by greater alcohol consumption (S1: 99.76 %, p  <.001; S2: 60.36 %, p  <.001). Crucially, in both studies, the direct effect of drinking to cope on alcohol problems was invariant across gender and countries., Conclusions: These findings suggest that individuals who endorse drinking to cope with negative affect are uniquely susceptible to the alcohol harm paradox, that is, greater alcohol problems which cannot be explained by greater alcohol consumption, and this susceptibility is common across gender and countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Ecological momentary assessment (EMA) studies have provided conflicting evidence for the mood regulation tenet that people drink in response to positive and negative moods. The current study examined mood-to-alcohol relationships idiographically to quantify the prevalence and intensity of relationships between positive and negative moods and drinking across individuals., Method: We used two EMA samples: 96 heavy drinking college students (sample 1) and 19 young adults completing an ecological momentary intervention (EMI) for drinking to cope (sample 2). Mood and alcohol use were measured multiple times per day for 4-6 weeks. Mood-alcohol relationships were examined using three different analytic approaches: standard multilevel modeling, group causal modeling, and idiographic causal modeling., Results: Both multilevel modeling and group causal modeling showed that participants in both samples drank in response to positive moods only. However, idiographic causal analyses revealed that only 63% and 21% of subjects (in samples 1 and 2, respectively) drank following any positive mood. Many subjects (24% and 58%) did not drink in response to either positive or negative mood in their daily lives, and very few (5% and 16%) drank in response to negative moods throughout the EMA protocol, despite sample 2 being selected specifically because they endorse drinking to cope with negative mood., Conclusion: Traditional group-level analyses and corresponding population-wide theories assume relative homogeneity within populations in mood-alcohol relationships, but this nomothetic approach failed to characterize accurately the relationship between mood and alcohol use in approximately half of the subjects in two samples that were demographically and clinically homogeneous. Given inconsistent findings in the mood-alcohol relationships to date, we conclude that idiographic causal analyses can provide a foundation for more accurate theories of mood and alcohol use. In addition, idiographic causal models may also help improve psychosocial treatments through direct use in clinical settings., (© 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Big trees and abundant species dominate forest structure and composition. As a result, their spatial distribution and interactions with other species and individuals may contribute disproportionately to the emergence of spatial heterogeneity in richness patterns. We tested scale-dependent spatial patterning and species richness structures to understand the role of individual trees (big trees) and species (abundant species) in driving spatial richness patterns on a 25 ha plot in a diverse tropical forest of Australia. The individual species area relationship (ISAR) was used to assess species richness in neighborhoods ranging from 1 to 50 m radii around all big trees (≥70 cm dbh, n  = 296) and all species with more than 100 individuals in the plot ( n  = 53). A crossed ISAR function was also used to compute species richness around big trees for trees of different size classes. Big individuals exert some spatial structuring on other big and mid-sized trees in local neighborhoods (up to 30 m and 16 m respectively), but not on small trees. While most abundant species were neutral with respect to richness patterns, we identified consistent species-specific signatures on spatial patterns of richness for 14 of the 53 species. Seven species consistently had higher than expected species richness in their neighborhood (species "accumulators"), and seven had lower than expected (species "repellers") across all spatial scales. Common traits of accumulators and repeller species suggest that niche partitioning along disturbance gradients is a primary mechanism driving spatial richness patterns, which is then manifested in large-scale spatial heterogeneity in species distributions across the plot., Competing Interests: The authors declare no competing financial or personal interests., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Purpose: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice., Methods: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK., Results: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T 2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions., Conclusions: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

We are not aware of any validated sexual health communication scales for use with young men who have sex with men (YMSM). We used data from an HIV prevention study in Lebanon with 226 YMSM aged 18-29 to assess the psychometric characteristics of our scale, Judgmental Communication with Peers about Sex (JCPS). The construct validity of the JCPS scale was supported by it being negatively correlated with general social support, percentage of alters perceived to be supportive, and the percentage of peers who are perceived to use condoms. The scale was positively correlated with gay-related discrimination, feeling part of the gay community, and gay social integration. These findings reflect a reliable, valid measure to assess judgmental sexual health communication between YMSM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the use of tocilizumab in a community hospital setting for critically ill patients with severe COVID-19., Design: A retrospective case series., Setting: Five community hospitals within 1 urban health system., Patients: Adult patients whom received tocilizumab between March 27th, 2020 to April 30th, 2020 for severe COVID-19., Interventions: None., Measurements and Main Results: Sixteen patients in total were evaluated from the 5 community hospitals. The mean (± SD) age of the patients was 53.9 ± 9.2 years, 56% were men, and the most common comorbidities present on admission were hypertension (31%) and diabetes mellitus (25%). All patients received at least 1 other treatment modality for COVID-19 (steroids, hydroxychloroquine, or convaslescent plasma). Additionally, all patients on admission to intensive care units had severe COVID-19 with 56% requiring mechanical ventilation with a pre-tocilizumab median (IQR) Pao 2 : Fio 2 of 84 (69 - 108.6), 19% requiring vasopressor support, and inflammatory markers (CRP, LDH, ferritin, and IL-6) were elevated. The median (IQR) tocilizumab dose was 400 mg (400-600) which correlated with a weight-based mean (± SD) dose of 5.4 mg/kg ± 1.3. Of the 16 patients that received tocilizumab, 8 (50%) were discharged home, 7 (44%) died, and 1 (6%) was still hospitalized at the end of data collection. Patients who died were more likely to be older 62 ± 2 years, female (57%), had a higher rate of mechanical ventilation (86%) and vasopressors (43%) use at baseline, and had a higher median (IQR) IL-6 level prior to tocilizumab administration 550 pg/mL (IQR 83-1924). There were no reported adverse drug reactions reported after the administration of tocilizumab for any patient., Conclusions: Our findings do not support the effectiveness of tocilizumab in treatment of severe COVID-19 infection in critically ill patients.

Perceived discrimination and medical mistrust are contributors to HIV inequities. The current study examined whether medical mistrust mediated the associations between perceived discrimination and adherence to antiretroviral therapy (ART) as well as care engagement in a sample of 304 Black adults living with HIV. Perceived discrimination and medical mistrust were measured using validated scales; ART adherence was electronically monitored for a month; care engagement was determined by medical record data. Results support significant total indirect effects from perceived discrimination (due to HIV-serostatus, race, sexual orientation) to ART adherence through three types of medical mistrust (towards healthcare organizations, one's physician, and HIV-specific mistrust). The total indirect effects were also significant for care engagement and were largely driven by mistrust towards one's own physician. Findings suggest interventions at the provider or healthcare organization levels should address medical mistrust to improve the health and well-being of Black Americans living with HIV., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We evaluated the effects of a culturally adapted evidence-based HIV prevention intervention (Mpowerment), named "Tayf", on condom use and HIV testing among young men who have sex with men (YMSM) in Beirut. A 2-year implementation of Tayf was carried out independently and in parallel with a research cohort of 226 YMSM who were surveyed at baseline and months 6, 12, 18 and 24 after Tayf initiation. Primary outcomes were (1) any condomless anal sex with HIV-positive or unknown status partners in the past 3 months, and (2) HIV testing in the past six months. Hierarchical logistic regression models examined the association of Tayf participation with the outcomes averaged across all assessments, and the moderating effect of Tayf participation on change in the outcomes over the follow-up period. A total of 331 YMSM attended at least one event, including 33% of the cohort. Tayf participation was associated with a higher rate of any condomless sex with HIV-positive or unknown status partners averaged across the five assessments, but there was no moderating effect of Tayf participation on change in this outcome over time. Tayf participation was associated with higher HIV testing when averaged across all assessments, but its interaction with time showed that the strength of this association diminished over time. In conclusion, Tayf proved feasible and acceptable in Beirut, but with limited effects. Further work is needed, including innovative publicity and marketing strategies, to bolster effects in high stigma settings where security and legal risks are prominent., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Socioeconomic deprivation is associated with greater alcohol problems despite lower alcohol consumption, but the mechanisms underpinning this alcohol harm paradox remain obscure. Fragmented published evidence collectively supports a multistage causal risk pathway wherein socioeconomic deprivation increases the probability of exposure to aversive experience, which promotes internalizing symptoms (depression and anxiety), which promotes drinking alcohol to cope with negative affect, which in turn accelerates the transition from alcohol use to dependence. To evaluate this proposed risk pathway, 219 hazardous drinkers from an undergraduate population completed questionnaires assessing these constructs in a single, cross sectional, online survey. Partial correlation coefficients revealed that each variable showed the strongest unique association with the next variable in the proposed multistage model, when adjusting for the other variables. Bootstrapped serial mediation analysis revealed that the indirect pathway linking all the variables in the proposed serial order was significant, while all other permutations were non-significant. Network centrality analysis corroborated the serial order of this indirect path. Finally, risk ratios estimated by categorizing the variables suggested that socioeconomic deprivation increased the risk of aversive experience by 32%, which increased the risk of internalizing symptoms by 180%, which increased the risk of drinking to cope by 64%, which increased susceptibility to alcohol dependence by 59%. These preliminary findings need to be corroborated by future research, nevertheless, they call for prevention strategies founded on social justice and the minimization of aversive experience in socially deprived individuals to mitigate mental health problems, maladaptive coping and addiction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shuai, Anker, Bravo, Kushner and Hogarth.)

This article describes the University of Minnesota Medical School Proposal Preparation Program (P3). P3 is designed to develop grant-writing skills for assistant professors preparing their first K- or R-series application to the National Institutes of Health (NIH). Three 4-month P3 cycles are conducted annually. For each cycle, a cohort of around 10 assistant professor participants and 5 regular faculty mentors meet for ten ~2-hour group sessions. Participants receive iterative oral and written feedback on their proposals in development within a small, interdisciplinary, group mentoring setting providing structure, accountability, guidance, and support. Between sessions, 1 peer and 1 mentor are assigned (on a rotating basis) to critique each participant's developing application. The sessions include a brief mentor-led presentation on a particular grant section followed by discussion of each participant's application conducted by the assigned reviewers. The cycle concludes with a mock NIH review session, in which each participant is matched with a University of Minnesota faculty content expert who critiques their completed application using NIH guidelines. In a survey sent to all past P3 participants as of 2018 (n = 194), 88% of respondents reported having submitted their P3-developed NIH grant, and 35% of these submitters reported funding success. A separate analysis of institutional data for all past P3 participants as of 2016 (n = 165) showed that 73% submitted at least 1 NIH proposal since completing P3 and that 43% of these had acquired NIH funding, for a combined total of $193 million in funding awarded. The estimated rate at which participants obtained funding for their P3-developed grant application (~35%) exceeds the national annual NIH grant funding rates (~20%) by approximately 50%. This article provides the practical information needed for other institutions to implement a P3-like program and presents a cost-benefit analysis showing the advantages of doing so., (Copyright © 2021 by the Association of American Medical Colleges.)

Purpose: To characterize the diffusion time-dependence in muscle in healthy adult volunteers, boys with Duchenne's muscular dystrophy (DMD), and age-matched controls in a clinically feasible acquisition time for pediatric applications., Methods: Diffusion data were acquired using a pulsed gradient stimulated echo diffusion preparation at 5 different diffusion times (70, 130, 190, 250, and 330 ms), at 4 different b-values (0, 200, 400, 600, and 800 s/mm 2 ) and 6 directions (orthogonal x, y, and z and diagonal xy, xz, and yz) and processed to obtain standard diffusion indices (mean diffusivity [MD] and fractional anisotropy [FA]) at each diffusion time., Results: Time-dependent diffusion was seen in muscle in healthy adult volunteers, boys with DMD, and age-matched controls. Boys with DMD showed reduced MD and increased FA values in comparison to age matched controls across a range of diffusion times. A diffusion time of Δ = 190 ms had the largest effect size., Conclusions: These results could be used to optimize diffusion imaging in this disease further and imply that these diffusion indices may become an important biomarker in monitoring progression in DMD in the future., (© 2021 International Society for Magnetic Resonance in Medicine.)

Microscopic diffusion anisotropy imaging using diffusion-weighted MRI and multidimensional diffusion encoding is a promising method for quantifying clinically and scientifically relevant microstructural properties of neural tissue. Several methods for estimating microscopic fractional anisotropy (µFA), a normalized measure of microscopic diffusion anisotropy, have been introduced but the differences between the methods have received little attention thus far. In this study, the accuracy and precision of µFA estimation using q-space trajectory encoding and different signal models were assessed using imaging experiments and simulations. Three healthy volunteers and a microfibre phantom were imaged with five non-zero b-values and gradient waveforms encoding linear and spherical b-tensors. Since the ground-truth µFA was unknown in the imaging experiments, Monte Carlo random walk simulations were performed using axon-mimicking fibres for which the ground truth was known. Furthermore, parameter bias due to time-dependent diffusion was quantified by repeating the simulations with tuned waveforms, which have similar power spectra, and with triple diffusion encoding, which, unlike q-space trajectory encoding, is not based on the assumption of time-independent diffusion. The truncated cumulant expansion of the powder-averaged signal, gamma-distributed diffusivities assumption, and q-space trajectory imaging, a generalization of the truncated cumulant expansion to individual signals, were used to estimate µFA. The gamma-distributed diffusivities assumption consistently resulted in greater µFA values than the second order cumulant expansion, 0.1 greater when averaged over the whole brain. In the simulations, the generalized cumulant expansion provided the most accurate estimates. Importantly, although time-dependent diffusion caused significant overestimation of µFA using all the studied methods, the simulations suggest that the resulting bias in µFA is less than 0.1 in human white matter., Competing Interests: Declaration of Competing Interest FS is an inventor on a patent related to the study., (Copyright © 2021. Published by Elsevier Inc.)

Sexual violence has been found to have psychosocial and sexual ramifications for men who have sex with men (MSM) but has not been studied in the Middle East. We assessed the prevalence and correlates of experiences of child and post-child sexual violence among young MSM residing in Beirut, Lebanon. In total, 226 MSM, aged 18 to 29, were recruited with long-chain peer referrals and administered a survey that included questions on history of being pressured to have sex, as well as specific forms of sexual harassment and abuse, in addition to measures of psychosocial functioning and sexual behavior. Logistic regression analysis was used to examine correlates of child sex abuse and experiences of sexual violence post-childhood; 17.3% experienced sexual abuse as a child (below age 13), while 63.3% experienced any form of sexual violence post-childhood-furthermore, 48.7% had experienced being forced or pressured to have sex during their lifetime, including 32.3% prior to age 18. Participants who experienced child sex abuse were more likely to experience abusive relationships in adulthood, as well as at least one type of sexual harassment/abuse post-childhood. Experience of any sexual violence post-childhood was correlated with greater recent sexuality-related discrimination and more recent male sex partners. These findings reveal a high prevalence of sexual violence among MSM in Beirut, both in childhood and post-childhood. More research within the Middle East is needed to better understand the drivers of sexual violence in this population, and how to best provide prevention and coping services.

MRI has been an essential diagnostic tool in healthcare for several decades. It offers unique insights into most tissues without the need for ionising radiation. Historically, MRI has been predominantly used qualitatively, images are formed to allow visual discrimination of tissues types and pathologies, rather than providing quantitative measurements. Increasingly, quantitative MRI (qMRI) is also finding clinical application, where images provide the basis for physical measurements of, e.g. tissue volume measures and represent aspects of tissue composition and microstructure. This article reviews some common current research and clinical applications of qMRI from the perspective of measurement science. qMRI not only offers additional information for radiologists, but also the opportunity for improved harmonisation and calibration between scanners and as such it is well-suited to large-scale investigations such as clinical trials and longitudinal studies. Realising these benefits, however, presents a new kind of technical challenge to MRI practioners. When measuring a parameter quantitatively, it is crucial that the reliability and reproducibility of the technique are well understood. Strictly speaking, a numerical result of a measurement is meaningless unless it is accompanied by a description of the associated measurement uncertainty. It is therefore necessary to produce not just estimates of physical properties in a quantitative image, but also their associated uncertainties. As the process of determining a physical property from the raw MR signal is complicated and multistep, estimation of uncertainty is challenging and there are many aspects of the MRI process that require validation. With the clinical implementation of qMRI techniques and its continued expansion, there is a clear and urgent need for metrology in this field.

The Middle East and North Africa (MENA) is one of only two global regions where rates of HIV are currently on the rise. In Lebanon, new HIV infections are increasing most rapidly among young men who have sex with men (YMSM). While, the majority of YMSM in Lebanon report having recently engaged in condomless anal intercourse, many report reluctance to seek HIV prevention services for fear of stigma and discrimination. Pre-exposure prophylaxis (PrEP) is an effective alternative HIV prevention strategy but there is a dearth of research looking at willingness to take PrEP among YMSM in MENA. This study is the first to delineate factors associated with willingness to take PrEP among a cohort of 218 YMSM recruited from Beirut, Lebanon. Over half (55.5%) reported willingness to take PrEP. At the bivariate level, knowledge of HIV risk, awareness of PrEP, being in a relationship, greater judgementalism about sex in communication with peers, greater number of types of gay-related discrimination experienced, sense of community among YMSM, having had recent condomless anal sex with positive or unknown status partner, and the use of substances just prior to or during sex were each associated with greater willingness to take PrEP. When entered into a linear regression analysis, use of substances just prior to or during sex and sense of community among YMSM remained significant predictors of PrEP willingness. Intervention efforts focused on increasing PrEP uptake among YMSM in MENA should consider the influence substance use and social factors on willingness to take PrEP.

Background: Medical mistrust, a result of systemic racism, is prevalent among Black Americans and may play a role in COVID-19 inequities. In a convenience sample of HIV-positive Black Americans, we examined associations of COVID-19-related medical mistrust with COVID-19 vaccine and COVID-19 treatment hesitancy and negative impacts of COVID-19 on antiretroviral therapy (ART) adherence., Methods: Participants were 101 HIV-positive Black Americans (age: M = 50.3 years; SD = 11.5; 86% cisgender men; 77% sexual minority) enrolled in a randomized controlled trial of a community-based ART adherence intervention in Los Angeles County, CA. From May to July 2020, participants completed telephone interviews on negative COVID-19 impacts, general COVID-19 mistrust (eg, about the government withholding information), COVID-19 vaccine and treatment hesitancy, and trust in COVID-19 information sources. Adherence was monitored electronically with the Medication Event Monitoring System., Results: Nearly all participants (97%) endorsed at least one general COVID-19 mistrust belief, and more than half endorsed at least one COVID-19 vaccine or treatment hesitancy belief. Social service and health care providers were the most trusted sources. Greater COVID-19 mistrust was related to greater vaccine and treatment hesitancy [b (SE) = 0.85 (0.14), P < 0.0001 and b (SE) = 0.88 (0.14), P < 0.0001, respectively]. Participants experiencing more negative COVID-19 impacts showed lower ART adherence, assessed among a subset of 49 participants [b (SE) = -5.19 (2.08), P = 0.02]., Discussion: To prevent widening health inequities, health care providers should engage with communities to tailor strategies to overcome mistrust and deliver evidence-based information, to encourage COVID-19 vaccine and treatment uptake., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The Fauresmith was a term first coined by archaeologists in the 1920s to describe a cultural development intermediate between the Earlier and Middle Stone Ages. From the late 1960s, many researchers abandoned the term in favor of sinking the Fauresmith within the Later Acheulean. More recently, however, some have supported the idea of the Fauresmith as the earliest Middle Stone Age, whereas other researchers continue to use the term to refer to a transitional technological development. In this article, we evaluate the status of the Fauresmith. We do this by describing a newly excavated assemblage from Canteen Kopje in the Northern Cape Province of South Africa and by comparing it with other assemblages published as Fauresmith. Although there is substantial variability across these assemblages, we present data to show that the relevant assemblages show the consistency of a regional technology that is indeed transitional between the Earlier and Middle Stone Ages. It includes prepared cores, blades, and very reduced numbers of large cutting tools compared with the Acheulean, and it often includes convergent flakes and retouched points. We argue that the Fauresmith, along with parallel developments both within and beyond Africa, is a term worth retaining to identify the slow process of decline of Acheulean technology in favor of a lighter toolkit, which includes varying degrees of more advanced core reduction strategies, larger numbers of formal tools, and hafting. Such developments are associated with populations linked to the development of Homo sapiens in Africa from ca. 600 to 160 ka., Competing Interests: Conflict of interest The authors declare no conflict of interest in this research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: To combine numerical simulations, in vitro and in vivo experiments to evaluate the feasibility of measuring diffusion exchange across the cell membrane with diffusion exchange spectroscopy (DEXSY)., Methods: DEXSY acquisitions were simulated over a range of permeabilities in nerve tissue and yeast substrates. In vitro measurements were performed in a yeast substrate and in vivo measurements in mouse tumor xenograft models, all at 9.4 T., Results: Diffusion exchange was observed in simulations over a physiologically relevant range of cell permeability values. In vitro and in vivo measures also provided evidence of diffusion exchange, which was quantified with the Diffusion Exchange Index (DEI)., Conclusions: Our findings provide preliminary evidence that DEXSY can be used to make in vivo measurements of diffusion exchange and cell membrane permeability., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Double diffusion encoding (DDE) MRI enables the estimation of microscopic diffusion anisotropy, yielding valuable information on tissue microstructure. A recent study proposed that the acquisition of rotationally invariant DDE metrics, typically obtained using a spherical "5-design," could be greatly simplified by assuming Gaussian diffusion, facilitating reduced acquisition times that are more compatible with clinical settings. Here, we aim to validate the new minimal acquisition scheme against the standard DDE 5-design, and to quantify the proposed method's noise robustness to facilitate future clinical use., Theory and Methods: DDE MRI experiments were performed on both ex vivo and in vivo rat brains at 9.4 T using the 5-design and the proposed minimal design and taking into account the difference in the number of acquisitions. The ensuing microscopic fractional anisotropy (μFA) maps were compared over a range of b-values up to 5000 s/mm 2 . Noise robustness was studied using analytical calculations and numerical simulations., Results: The minimal protocol quantified μFA at an accuracy comparable to the estimates obtained by means of the more theoretically robust DDE 5-design. μFA's sensitivity to noise was found to strongly depend on compartment anisotropy and tensor magnitude in a nonlinear manner. When μFA < 0.75 or when mean diffusivity is particularly low, very high signal-to-noise ratio is required for precise quantification of µFA., Conclusion: Our work supports using DDE for quantifying microscopic diffusion anisotropy in clinical settings but raises hitherto overlooked precision issues when measuring μFA with DDE and typical clinical signal-to-noise ratio., (© 2019 International Society for Magnetic Resonance in Medicine.)

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 ​min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm 2 s -1 ) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, H n , but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 ​s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena., Competing Interests: Declaration of competing interest The QDI technique is covered by UK patent application GB1909982.9 (inventors: Dr T.R. Barrick, Prof F.A. Howe, Dr M.G. Hall, Dr C. Ingo, Prof R.L. Magin). Patent pending August 28, 2019., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time-dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age-related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time-dependent diffusion MRI to quantify age and disease-related changes in hind-limb muscle microstructure between dystrophic (mdx) and wild-type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time-dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion-gradient orientation at six diffusion times (Δ; range: 25-350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T 2 , using Student's t test, one-way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind-limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5-15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T 2 and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non-invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ., (© 2020 John Wiley & Sons, Ltd.)

Background: Aspects of sexual identity development, including integration into gay community, have been found to be associated with sexual risk behavior among men who have sex with men (MSM), but not in the Middle East., Method: Drawing on the minority stress model and integrated theory of health behavior, we examined the relationships between measures of sexual identity development and HIV protective behaviors (condomless anal sex and HIV testing) and the mediating roles of HIV knowledge, peer judgmentalism, and discrimination, in a sample of 226 young MSM in Beirut, Lebanon. A cross-sectional, mediation analysis was conducted using a bootstrapping approach and logistic regression models., Results: Fifteen percent of the sample reported recent condomless anal sex with partners whose HIV status was positive or unknown, and 82.3% had ever been tested for HIV. Multivariate logistic regression analysis showed that greater integration into the gay community was significantly associated with having recent condomless anal sex with positive/unknown HIV status partners and having any history of HIV testing, after controlling for covariates. Knowledge of HIV risk was associated with gay integration as well as both condomless anal sex with positive or unknown HIV status partners and any history of HIV testing, but it only served as a (partial) mediator of HIV testing. Peer judgmental communication about sex and sexuality-related discrimination were related in bivariate analysis to gay integration and condomless anal sex, but they too did not prove to be significant mediators of the relationship between these two constructs., Conclusion: These findings highlight the potential sexual health benefits and vulnerabilities associated with increased integration into the gay community for young MSM in Beirut and the need to better understand how to increase HIV knowledge while limiting its potential to increase sexual risk behavior.

Introduction: We describe a case of alemtuzumab (Campath®) hypersensitivity requiring desensitization within the medical intensive care unit (MICU) in a patient with T-cell prolymphocytic leukemia., Case Report: We adopted a desensitization protocol from Gutierrez-Fernandez et al., which included three aliquots (0.15 mg intravenously (IV), 1.5 mg IV, and 28.5 mg IV) given approximately 1 h apart on day 1 followed by a full 30 mg dose IV on day 3. Unlike prior attempts to administer alemtuzumab to this patient, she tolerated the medication well and did not require any rescue medications., Management and Outcome: Successful plan development required a significant amount of strategic communication between hematology/oncology and MICU-related physicians, pharmacists, and nurses to ensure a safe and effective desensitization. The first step of planning required creation of a desensitization order set with directions for medication preparation and administration, premedications, and available medications in the event of an adverse reaction or anaphylaxis. Anaphylactoid-related medications were prepared at bedside and ready for administration prior to beginning the desensitization. Alemtuzumab was compounded in a chemotherapy-certified hood and verified by at least two chemotherapy-certified pharmacists. Foreword planning was also necessary to ensure multiple people were available or present at bedside for the desensitization, including a chemotherapy-certified nurse, a second chemotherapy-certified nurse for verification, a critical care-certified pharmacist, a pulmonary/critical care attending physician, and hematology attending physician., Discussion: This case exemplifies the importance of clear and coordinated communication between different healthcare fields to safely and effectively complete extensive protocols such as desensitization strategies.

Neurofibromatosis Type 1 (NF1)-related Malignant Peripheral Nerve Sheath Tumors (MPNST) are highly resistant sarcomas that account for significant mortality. The mechanisms of therapy resistance are not well-understood in MPNSTs, particularly with respect to kinase inhibition strategies. In this study, we aimed to quantify the impact of both the genomic context and targeted therapy on MPNST resistance using reverse phase phosphoproteome array (RPPA) analysis. We treated tumorgrafts from three genetically engineered mouse models using MET (capmatinib) and MEK (trametinib) inhibitors and doxorubicin, and assessed phosphosignaling at 4 h, 2 days, and 21 days. Baseline kinase signaling in our mouse models recapitulated an MET-addicted state (NF1-MET), P53 mutation (NF1-P53), and HGF overexpression (NF1). Following perturbation with the drug, we observed broad and redundant kinome adaptations that extended well beyond canonical RAS/ERK or PI3K/AKT/mTOR signaling. MET and MEK inhibition were both associated with an initial inflammatory response mediated by kinases in the JAK/STAT pathway and NFkB. Growth signaling predominated at the 2-day and 21-day time points as a result of broad RTK and intracellular kinase activation. Interestingly, AXL and NFkB were strongly activated at the 2-day and 21-day time points, and tightly correlated, regardless of the treatment type or genomic context. The degree of kinome adaptation observed in innately resistant tumors was significantly less than the surviving fractions of responsive tumors that exhibited a latency period before reinitiating growth. Lastly, doxorubicin resistance was associated with kinome adaptations that strongly favored growth and survival signaling. These observations confirm that MPNSTs are capable of profound signaling plasticity in the face of kinase inhibition or DNA damaging agent administration. It is possible that by targeting AXL or NFkB, therapy resistance can be mitigated.

Applications of fractional calculus in magnetic resonance imaging (MRI) have increased over the last twenty years. From the mathematical, computational, and biophysical perspectives, fractional calculus provides new tools for describing the complexity of biological tissues (cells, organelles, membranes and macromolecules). Specifically, fractional order models capture molecular dynamics (transport, rotation, and vibration) by incorporating power law convolution kernels into the time and space derivatives appearing in the equations that govern nuclear magnetic resonance (NMR) phenomena. Hence, it is natural to expect fractional calculus models of relaxation and diffusion to be applied to problems in NMR and MRI. Early studies considered the fractal dimensions of multi-scale materials in the non-linear growth of the mean squared displacement, assumed power-law decays of the spectral density, and suggested stretched exponential signal relaxation to describe non-Gaussian behavior. Subsequently, fractional order generalization of the Bloch, and Bloch-Torrey equations were developed to characterize NMR (and MRI) relaxation and diffusion. However, even for simple geometries, analytical solutions of fractional order equations in time and space are difficult to obtain, and predictions of the corresponding changes in image contrast are not always possible. Currently, a multifaceted approach using coarse graining, simulation, and accelerated computation is being developed to identify 'imaging' biomarkers of disease. This review surveys the principal fractional order models used to describe NMR and MRI phenomena, identifies connections and limitations, and finally points to future applications of the approach.

In 2012, our research with young men who have sex with men (YMSM) in Beirut showed high rates of recent condomless anal sex and low rates of recent HIV testing. In 2017, we collected data from YMSM to assess for temporal changes and sociodemographic correlates. Propensity score weighting was used to eliminate any sociodemographic differences between the 2012 (n = 164) and 2017 (n = 226) samples of YMSM (age 18-29) recruited with long-chain peer referral sampling. Regression analysis was used to examine sociodemographic correlates of recent condomless anal sex and HIV testing using the 2017 sample, and whether these behaviors differed between the samples. Compared to the 2012 sample, the 2017 sample was about half as likely to report any condomless anal sex in the past 3 months with partners whose HIV status was positive or unknown (14% vs. 23%; OR [95%CI] 0.56 [0.32, 0.98]), and nearly 2.5 times as likely to report HIV testing in the past 6 months (48% vs. 27%; OR [95%CI] 2.44 [1.46, 4.10]). In the 2017 sample, any recent condomless anal sex with partners whose HIV status was positive or unknown was associated with employment and Christian religious affiliation. Low income was the sole correlate of having recently tested for HIV. These findings suggest a temporal trend toward increased HIV protective behaviors among YMSM in Beirut over the past 5 years. Further inroads could be secured if HIV prevention programming targeted economic influences.

A substantial number of people who have problems with alcohol also experience strong anxiety and mood problems. This article provides an overview of the evolving perspectives of this association in the context of three related disciplines-psychiatry, psychology, and neuroscience. Psychiatric and epidemiological studies show that having either an anxiety- or alcohol-related diagnosis elevates the prospective risk for developing the other disorder. From the psychological perspective, behavioral research demonstrates that drinking to cope with negative affect is a potent marker for current and future problems with alcohol. Neuroscientific research implicates overlapping neurobiological systems and psychological processes in promoting the rise of negative affect and alcohol misuse. The psychiatric perspective that alcohol misuse and co-occurring anxiety represent neurobiologically distinct diagnostic conditions has dominated the field for many decades. However, recent research provides increasing support for the neuroscientific perspective that these conditions share underlying, mutually exacerbating, neurobiological processes., Competing Interests: Financial Disclosure The authors declare that they have no competing financial interests.