A Multi-Sample Comparison and Rasch Analysis of the Evaluation of Children's Listening and Processing Skills Questionnaire.

OBJECTIVES: Assessing listening difficulties and associated complaints can be challenging. Often, measures of peripheral auditory functions are within normal ranges, making clinicians feel unsure about proper management strategies. The range and nature of observed or experienced difficulties might be better captured using a qualitative measure. The Evaluation of Children's Listening and Processing Skills (ECLiPS) questionnaire was designed to broadly profile the auditory and cognitive problems often present in children with listening difficulties. This 38-item questionnaire was initially standardized in British children aged 6 to 11 years, was subsequently modified for use with North-American children, and was recently translated into Flemish-Dutch. This study aimed to compare typical scores of the Flemish version with the UK and US versions, and to evaluate and compare its psychometric quality based on Rasch analysis. DESIGN: We selected 112 Flemish children aged 6 to 11 years with verified normal hearing and typical development, and asked two caregivers of every child to fill out the ECLiPS. Data from two comparator samples were analyzed, including responses for 71 North-American children and 650 British children. Typical values for ECLiPS factors and aggregates were determined as a function of age and gender, and meaningful differences across samples were analyzed. Rasch analyses were performed to evaluate whether ECLiPS response categories work as intended, and whether item scores fit a linear equal interval measurement scale that works the same way for everyone. Item and person metrics were derived, including separation and reliability indices. We investigated whether items function similarly across linguistically and culturally different samples. RESULTS: ECLiPS scores were relatively invariant to age. Girls obtained higher scores compared with boys, mainly for items related to memory and attention, and pragmatic and social skills. Across ECLiPS versions, the most pronounced differences were found for items probing social skills. With respect to its psychometric quality, ECLiPS response categories work as intended, and ECLiPS items were found to fit the Rasch measurement scale. Cultural differences in responses were noted for some items, belonging to different factors. Item separation and reliability indices generally pointed toward sufficient variation in item difficulty. In general, person separation (and reliability) metrics, quantifying the instrument's ability to distinguish between poor and strong performers (in a reproducible manner), were low. This is expected from samples of typically developing children with homogeneous and high levels of listening ability. CONCLUSIONS: Across the languages assessed here, the ECLiPS caregiver questionnaire was verified to be a psychometrically valid qualitative measure to assess listening and processing skills, which can be used to support the assessment and management of elementary school children referred with LiD.

Correction: Cingulate transcranial direct current stimulation in adults with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0269491.].

Alzheimer-Type Cerebral Amyloidosis in the Context of HIV Infection: Implications for a Proposed New Treatment Approach.

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aß42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.

User Experience of Persons Using Ingestible Sensor-Enabled Pre-Exposure Prophylaxis to Prevent HIV Infection: Cross-Sectional Survey Study.

Background: A digital health technology's success or failure depends on how it is received by users. objectives: We conducted a user experience (UX) evaluation among persons who used the Food and Drug Administration-approved Digital Health Feedback System incorporating ingestible sensors (ISs) to capture medication adherence, after they were prescribed oral pre-exposure prophylaxis (PrEP) to prevent HIV infection. We performed an association analysis with baseline participant characteristics, to see if "personas" associated with positive or negative UX emerged. Methods: UX data were collected upon exit from a prospective intervention study of adults who were HIV negative, prescribed oral PrEP, and used the Digital Health Feedback System with IS-enabled tenofovir disoproxil fumarate plus emtricitabine (IS-Truvada). Baseline demographics; urine toxicology; and self-report questionnaires evaluating sleep (Pittsburgh Sleep Quality Index), self-efficacy, habitual self-control, HIV risk perception (Perceived Risk of HIV Scale 8-item), and depressive symptoms (Patient Health Questionnaire-8) were collected. Participants with ≥28 days in the study completed a Likert-scale UX questionnaire of 27 questions grouped into 4 domain categories: overall experience, ease of use, intention of future use, and perceived utility. Means and IQRs were computed for participant total and domain subscores, and linear regressions modeled baseline participant characteristics associated with UX responses. Demographic characteristics of responders versus nonresponders were compared using the Fisher exact and Wilcoxon rank-sum tests. Results: Overall, 71 participants were enrolled (age: mean 37.6, range 18-69 years; n=64, 90% male; n=55, 77% White; n=24, 34% Hispanic; n=68, 96% housed; and n=53, 75% employed). No demographic differences were observed in the 63 participants who used the intervention for ≥28 days. Participants who completed the questionnaire were more likely to be housed (52/53, 98% vs 8/10, 80%; P=.06) and less likely to have a positive urine toxicology (18/51, 35% vs 7/10, 70%; P=.08), particularly methamphetamine (4/51, 8% vs 4/10, 40%; P=.02), than noncompleters. Based on IQR values, ≥75% of participants had a favorable UX based on the total score (median 3.78, IQR 3.17-4.20), overall experience (median 4.00, IQR 3.50-4.50), ease of use (median 3.72, IQR 3.33-4.22), and perceived utility (median 3.72, IQR 3.22-4.25), and ≥50% had favorable intention of future use (median 3.80, IQR 2.80-4.40). Following multipredictor modeling, self-efficacy was significantly associated with the total score (0.822, 95% CI 0.405-1.240; P<.001) and all subscores (all P<.05). Persons with more depressive symptoms reported better perceived utility (P=.01). Poor sleep was associated with a worse overall experience (-0.07, 95% CI -0.133 to -0.006; P=.03). Conclusions: The UX among persons using IS-enabled PrEP (IS-Truvada) to prevent HIV infection was positive. Association analysis of baseline participant characteristics linked higher self-efficacy with positive UX, more depressive symptoms with higher perceived utility, and poor sleep with negative UX.

Diagnostic accuracy of digital technologies compared with 12-lead ECG in the diagnosis of atrial fibrillation in adults: A protocol for a systematic review.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. AF increases the risk of stroke 5-fold, though the risk can be reduced with appropriate treatment. Therefore, early diagnosis is imperative but remains a global challenge. In low-and middle-income countries (LMICs), a lack of diagnostic equipment and under-resourced healthcare systems generate further barriers. The rapid development of digital technologies that are capable of diagnosing AF remotely and cost-effectively could prove beneficial for LMICs. However, evidence is lacking on what digital technologies exist and how they compare in regards to diagnostic accuracy. We aim to systematically review the diagnostic accuracy of all digital technologies capable of AF diagnosis. METHODS: MEDLINE, Embase and Web of Science will be searched for eligible studies. Free text terms will be combined with corresponding index terms where available and searches will not be limited by language nor time of publication. Cohort or cross-sectional studies comprising adult (≥18 years) participants will be included. Only studies that use a 12-lead ECG as the reference test (comparator) and report outcomes of sensitivity, specificity, the diagnostic odds ratio (DOR) or the positive and negative predictive value (PPV and NPV) will be included (or if they provide sufficient data to calculate these outcomes). Two reviewers will independently assess articles for inclusion, extract data using a piloted tool and assess risk of bias using the QUADAS-2 tool. The feasibility of a meta-analysis will be determined by assessing heterogeneity across the studies, grouped by index device, diagnostic threshold and setting. If a meta-analysis is feasible for any index device, pooled sensitivity and specificity will be calculated using a random effect model and presented in forest plots. DISCUSSION: The findings of our review will provide a comprehensive synthesis of the diagnostic accuracy of available digital technologies capable for diagnosing AF. Thus, this review will aid in the identification of which devices could be further trialed and implemented, particularly in a LMIC setting, to improve the early diagnosis of AF. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration number is CRD42021290542. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290542.

Development and impact of a tailored eHealth resource on fibromyalgia patient's self-management and self-efficacy: A mixed methods approach.

Aim: To develop an eHealth resource to support fibromyalgia patients and explore it for usability and impact on their self-management and self-efficacy. Background: Fibromyalgia is a complex, non-progressive chronic condition characterised by a bewildering array of symptoms for patients to self-manage. International guidelines recommend patients receive illness-specific information once diagnosed to promote self-management and improve health-related quality of life. Design: A 3-phase mixed methods exploratory sequential design. Methods: Qualitative interviews explored the information and self-management needs of fibromyalgia patients attending a large tertiary hospital in Dublin. Identified themes together with an extensive review of the literature of interventions proven to be impactful by patients with fibromyalgia were utilised in the design and development of the eHealth resource. The resource was tested for usability and impact using pre and post-intervention outcomes measures. Results: Patient interviews highlighted a lack of easy accessible evidenced information to support self-management implicating the urgent need for a practical solution through development of a tailored eHealth resource. Six themes emerged for inclusion; illness knowledge, primary symptoms, treatment options, self-management strategies, practical support and reliable resources. Forty-five patients who tested the site for usability and impact demonstrated a statistically significant improvement in self-efficacy after 4 weeks access with a medium positive effect size. Patients with the most severe fibromyalgia impact scores pre-intervention demonstrated the most improvement after 4 weeks. Patients gave the resource a System Usability Score A rating, highly recommending it for fellow patients diagnosed with fibromyalgia. Conclusions: The study demonstrated how the development of a novel eHealth resource positively impacted fibromyalgia patients' self-efficacy to cope with this debilitating condition. Impact: This study suggests that access to eHealth can positively impact patients self-efficacy, has the potential to be a template for eHealth development in other chronic conditions, supporting advanced nurse practitioners working in chronic disease management.

High-entropy alloy screening for halide perovskites.

As the concept of high-entropy alloying (HEA) extends beyond metals, new materials screening methods are needed. Halide perovskites (HP) are a prime case study because greater stability is needed for photovoltaics applications, and there are 322 experimentally observed HP end-members, which leads to more than 1057 potential alloys. We screen HEAHP by first calculating the configurational entropy of 106 equimolar alloys with experimentally observed end-members. To estimate enthalpy at low computational cost, we turn to the delta-lattice parameter approach, a well-known method for predicting III-V alloy miscibility. To generalize the approach for non-cubic crystals, we introduce the parameter of unit cell volume coefficient of variation (UCV), which does a good job of predicting the experimental HP miscibility data. We use plots of entropy stabilization versus UCV to screen promising alloys and identify 102 HEAHP of interest.

Childhood Listening and Associated Cognitive Difficulties Persist Into Adolescence.

OBJECTIVE: Listening difficulty (LiD) refers to the challenges individuals face when trying to hear and comprehend speech and other sounds. LiD can arise from various sources, such as hearing sensitivity, language comprehension, cognitive function, or auditory processing. Although some children with LiD have hearing loss, many have clinically normal audiometric thresholds. To determine the impact of hearing and cognitive factors on LiD in children with a clinically normal audiogram, we conducted a longitudinal study. The Evaluation of Children's Listening & Processing Skills (ECLiPS), a validated and standardized caregiver evaluation tool, was used to group participants as either LiD or typically developing (TD). Our previous study aimed to characterize LiD in 6- to 13-year-old children during the project's baseline, cross-sectional phase. We found that children with LiD needed a higher signal-to-noise ratio during speech-in-speech tests and scored lower on all assessed components of the NIH Cognition Toolbox than TD children. The primary goal of this study was to examine if the differences between LiD and TD groups are temporary or enduring throughout childhood. DESIGN: This longitudinal study had three data collection waves for children with LiD and TD aged 6 to 13 years at Wave 1, followed by assessments at 2-year (Wave 2) and 4-year (Wave 3) intervals. Primary analysis focused on data from Waves 1 and 2. Secondary analysis encompassed all three waves despite high attrition at Wave 3. Caregivers completed the ECLiPS, while participants completed the Listening in Spatialized Noise-Sentences (LiSN-S) test and the NIH-Toolbox Cognition Battery during each wave. The analysis consisted of (1) examining longitudinal differences between TD and LiD groups in demographics, listening, auditory, and cognitive function; (2) identifying functional domains contributing to LiD; and (3) test-retest reliability of measures across waves. Mixed-effect models were employed to analyze longitudinal data. RESULTS: The study enrolled 169 participants, with 147, 100, and 31 children completing the required testing during Waves 1, 2, and 3, respectively. The mean ages at these waves were 9.5, 12.0, and 14.0 years. On average, children with LiD consistently underperformed TD children in auditory and cognitive tasks across all waves. Maternal education, auditory, and cognitive abilities independently predicted caregiver-reported listening skills. Significant correlations between Waves 1 and 2 confirmed high, long-term reliability. Secondary analysis of Wave 3 was consistent with the primary analyses of Waves 1 and 2, reinforcing the enduring nature of listening difficulties. CONCLUSION: Children with LiD and clinically normal audiograms experience persistent auditory, listening, and cognitive challenges through at least adolescence. The degree of LiD can be independently predicted by maternal education, cognitive processing, and spatial listening skills. This study underscores the importance of early detection and intervention for childhood LiD and highlights the role of socioeconomic factors as contributors to these challenges.

Feeding Ration Impacts Larval Pimephales Promelas 7-Day Subchronic Growth Endpoint: Case Study with Perfluorooctanesulfonic Acid.

The larval fathead minnow, Pimephales promelas, 7-day subchronic survival and growth standard toxicity test method is commonly used for research and regulatory testing of effluents and compounds, including emerging contaminants such as Perfluorooctanesulfonic Acid (PFOS). Existing feeding guidelines for testing are described in multiple methods but are open to interpretation. The current study sought to determine the impact of feeding ration on P. promelas survival and biomass during a subchronic exposure to PFOS. The study was conducted in two phases: (1) a control experiment to determine the most significant feeding ration factors that maximize biomass, with consideration to laboratory logistics, and (2) application of down-selected feeding rations in a PFOS exposure to determine toxicity reference values. The control optimization study supported that feeding ration and feeding frequency were significant factors in fish biomass. In the subsequent PFOS study, fish were fed a high or low ration of Artemia twice daily, while exposed to 0.3 to 3.4 mg/L PFOS. Fish fed a high ration of Artemia had significantly (p < 0.05) greater biomass than fish fed a low ration in all exposure concentrations except 3.4 mg/L, where survival was low in both treatments. The feeding ration was not a significant factor on the survival endpoint for either treatment, but the PFOS concentration was (p < 0.0001) (high ration LC50 = 2.44 mg/L; low ration LC50 = 2.25 mg/L). These findings contribute to a better understanding of the impact feeding ration has in toxicity assessments and downstream regulatory decisions.

Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models.

Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Access to care and impact on HIV treatment interruptions during the COVID-19 pandemic among people living with HIV in British Columbia.

INTRODUCTION: The COVID-19 pandemic has changed healthcare service delivery. We examined the overall impact of COVID-19 on people living with HIV in British Columbia (BC), Canada, with a special focus on the potential impact of COVID-19 on antiretroviral treatment interruptions (TIs). METHODS: Purposive sampling was used to enrol people living with HIV aged ≥19 years across BC into the STOP HIV/AIDS Program Evaluation study between January 2016 and September 2018. Participants completed surveys at baseline enrolment and 18 and 36 months later. Additional COVID-19 questions were added to the survey in October 2020. TIs were defined as >60 days late for antiretroviral therapy (ART) refill using data from the BC HIV Drug Treatment Program. Generalized linear mixed models were used to examine trends in TIs over time and associations with reported health service access. RESULTS: Of 581 participants, 6.1%-7.7% experienced a TI during each 6-month period between March 2019 and August 2021. The frequency of TIs did not statistically increase during the COVID-19 epidemic. Among the 188 participants who completed the COVID-19 questionnaire, 32.8% reported difficulty accessing healthcare during COVID-19, 9.7% reported avoiding continuing a healthcare service due to COVID-19-related concerns, and 74.6% reported using virtual healthcare services since March 2020. In multivariable analysis, the odds of a TI in any 6-month period were not significantly different from March to August 2019. None of the reported challenges to healthcare services were associated with TIs. CONCLUSIONS: Although some participants reported challenges to accessing services or avoidance of services due to COVID-19, TIs were not more likely during COVID-19 than before.

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV.

BACKGROUND: Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence. METHODS: Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations. RESULTS: Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable. CONCLUSION: IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence. CLINICAL TRIALS REGISTRATION: NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.

Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterized by sparse lymphocytes and high tumor-associated neutrophil (TAN) infiltration, had tumor cells spatially separated from vasculature and exhibited low spatial intratumor heterogeneity. TAN-high LUSC had frequent PIK3CA mutations. TAN-high tumors harbored recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune, and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis. SIGNIFICANCE: This study provides novel insights into the spatial organization of the lung cancer TME in the context of tumor immunogenicity, tumor heterogeneity, and cancer evolution. Pairing the tumor evolutionary history with the spatially resolved TME suggests mechanistic hypotheses for tumor progression and metastasis with implications for patient outcome and treatment. This article is featured in Selected Articles from This Issue, p. 897.

Impact of screening and doxycycline prevention on the syphilis epidemic among men who have sex with men in British Columbia: a mathematical modelling study.

Background: Men who have sex with men (MSM) in British Columbia (BC) are disproportionately affected by infectious syphilis and HIV. In this study, we developed a co-interaction model and evaluated the impact and effectiveness of possible interventions among different MSM subgroups on the syphilis epidemic. Methods: We designed a deterministic compartmental model, which stratified MSM by HIV status and HIV pre-exposure prophylaxis (HIV-PrEP) usage into (1) HIV-negative/unaware MSM (HIV-PrEP not recommended, not on HIV-PrEP), (2) HIV-negative/unaware MSM with HIV-PrEP recommended (not on HIV-PrEP), (3) HIV-negative/unaware MSM actively on HIV-PrEP, and (4) MSM diagnosed with HIV. We estimated the effect of scaling up syphilis testing frequency from Status Quo to six-, four-, and three-months, increasing the percentage of MSM using doxycycline prevention (Doxy-P) to 25%, 50%, and 100% of the target level, and a combination of both among subgroups (2)-(4). We also assessed the impact of these interventions on the syphilis incidence rates from 2020 to 2034 in comparison to the Status Quo scenario where no intervention was introduced. Findings: Under the Status Quo scenario, with the expansion of the HIV-PrEP program to improve syphilis testing, the syphilis incidence rate was estimated to peak at 16.1 [Credible Interval (CI):14.2-17.9] per 1,000 person-years (PYs) in 2023 and decrease to 6.7 (CI:3.8-10.9) per 1,000 PYs by 2034. The syphilis incidence rate in 2034 was estimated at 0.7 (0.3-1.3) per 1,000 PYs if MSM diagnosed with HIV could be tested every four months, and at 1.5 (0.7-3.0) per 1,000 PYs if HIV-negative/unaware MSM actively on HIV-PrEP could be tested every three months. By achieving 100% of the target coverage of Doxy-P, the syphilis incidence rate was estimated at 1.4 (0.5-3.4) if focusing on MSM diagnosed with HIV, and 2.6 (1.2-5.1) per 1,000 PYs if focusing on HIV-negative/unaware MSM actively on HIV-PrEP. Under the combined interventions, the syphilis incidence rate could be as low as 0.0 (0.0-0.1) and 0.8 (0.3-1.8) per 1,000 PYs, respectively. Interpretation: The HIV-PrEP program in BC plays a crucial role in increasing syphilis testing frequency among high-risk MSM and reducing syphilis transmission among this group. In addition, introducing Doxy-P can be an effective complementary strategy to minimize syphilis incidence, especially among MSM diagnosed with HIV. Funding: This work was funded by the Canadian Institutes of Health Research.

Transcutaneous Ablation of Lung Tissue in a Porcine Model Using Magnetic-Resonance-Guided Focused Ultrasound (MRgFUS).

Focused ultrasound (FUS) is a minimally invasive treatment that utilizes high-energy ultrasound waves to thermally ablate tissue. Magnetic resonance imaging (MRI) guidance may be combined with FUS (MRgFUS) to increase its accuracy and has been proposed for lung tumor ablation/debulking. However, the lungs are predominantly filled with air, which attenuates the strength of the FUS beam. This investigation aimed to test the feasibility of a new approach using an intentional lung collapse to reduce the amount of air inside the lung and a controlled hydrothorax to create an acoustic window for transcutaneous MRgFUS lung ablation. Eleven pigs had one lung mechanically ventilated while the other lung underwent a controlled collapse and subsequent hydrothorax of that hemisphere. The MRgFUS lung ablations were then conducted via the intercostal space. All the animals recovered well and remained healthy in the week following the FUS treatment. The location and size of the ablations were confirmed one week post-treatment via MRI, necropsy, and histological analysis. The animals had almost no side effects and the skin burns were completely eliminated after the first two animal studies, following technique refinement. This study introduces a novel methodology of MRgFUS that can be used to treat deep lung parenchyma in a safe and viable manner.

Understanding the effect of density functional choice and van der Waals treatment on predicting the binding configuration, loading, and stability of amine-grafted metal organic frameworks.

Metal organic frameworks (MOFs) are crystalline, three-dimensional structures with high surface areas and tunable porosities. Made from metal nodes connected by organic linkers, the exact properties of a given MOF are determined by node and linker choice. MOFs hold promise for numerous applications, including gas capture and storage. M2(4,4'-dioxidobiphenyl-3,3'-dicarboxylate)-henceforth simply M2(dobpdc), with M = Mg, Mn, Fe, Co, Ni, Cu, or Zn-is regarded as one of the most promising structures for CO2 capture applications. Further modification of the MOF with diamines or tetramines can significantly boost gas species selectivity, a necessity for the ultra-dilute CO2 concentrations in the direct-air capture of CO2. There are countless potential diamines and tetramines, paving the way for a vast number of potential sorbents to be probed for CO2 adsorption properties. The number of amines and their configuration in the MOF pore are key drivers of CO2 adsorption capacity and kinetics, and so a validation of computational prediction of these quantities is required to suitably use computational methods in the discovery and screening of amine-functionalized sorbents. In this work, we study the predictive accuracy of density functional theory and related calculations on amine loading and configuration for one diamine and two tetramines. In particular, we explore the Perdew-Burke-Ernzerhof (PBE) functional and its formulation for solids (PBEsol) with and without the Grimme-D2 and Grimme-D3 pairwise corrections (PBE+D2/3 and PBEsol+D2/3), two revised PBE functionals with the Grimme-D2 and Grimme-D3 pairwise corrections (RPBE+D2/3 and revPBE+D2/3), and the nonlocal van der Waals correlation (vdW-DF2) functional. We also investigate a universal graph deep learning interatomic potential's (M3GNet) predictive accuracy for loading and configuration. These results allow us to identify a useful screening procedure for configuration prediction that has a coarse component for quick evaluation and a higher accuracy component for detailed analysis. Our general observation is that the neural network-based potential can be used as a high-level and rapid screening tool, whereas PBEsol+D3 gives a completely qualitatively predictive picture across all systems studied, and can thus be used for high accuracy motif predictions. We close by briefly exploring the predictions of relative thermal stability for the different functionals and dispersion corrections.

Disparities in Metabolic Syndrome and Neurocognitive Function Among Older Hispanics/Latinos with Human Immunodeficiency Virus.

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50-75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = -3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = -3.39, SE = 1.31, p = 0.01) and MetS (B = -2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.