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Background: In the USA, many states, including Colorado, have increased criminal penalties for illicit opioid possession, which may alter overdose risk. We aimed to evaluate the relationship between Colorado's increased drug-related criminal legal penalties, risk of overdose, and substance use patterns., Methods: We used concept mapping - a mixed-methods approach used to develop a conceptual understanding of an issue from a community lens - to engage with people with living and/or lived experience with the criminal legal system, substance use, and/or overdose, their loved ones, and service providers. In facilitated discussion, we used the prompt: "Do you see overdose and substance use, in Colorado, being impacted by an individual's involvement with the criminal legal system?" Participants - recruited from community-based organizations - identified, rated, sorted, and categorized factors affecting criminal legal involvement, substance use, and/or overdose in their community. We used groupwisdom to develop concept maps and to analyze findings., Results: Twenty-four individuals (ages 18-70) participated; most had living and/or lived experience. Participants identified 100 distinct factors, which were sorted into 9 clusters: societal impacts of criminal legal involvement, lifesaving benefits to decreased criminal legal penalties, environmental barriers of criminal legal involvement, structural barriers to recovery services, essential culturally aware community-based services, strategic allocation of funding, strategies to improve law enforcement's impact, changing policies to keep law enforcement accountable and better educate law enforcement on community culture, and community issues with law enforcement to prioritize. Of the 40 most influential and common factors, most related to structural impacts of criminal legal involvement and barriers to recovery (e.g., long waitlists, job loss)., Conclusions: Using concept mapping, we worked with community members to identify and prioritize factors associated with substance use and overdose amidst increasing drug-related criminal legal penalties. These insights (e.g., law enforcement's role should be acting as a bridge to mental health and recovery services) are critical for policymakers and service providers, as they speak to the need for investing in re-entry services, harm reduction services, and co-responder models for behavioral health crises., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Colorado Multiple Institutional Review Board (COMIRB no. 22–1696). Written informed consent was obtained from participants prior to data collection. Research conformed to the principles of the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Photoelectrochemical (PEC) water splitting provides a promising strategy for H 2 production. However, its performance is limited by severe carrier recombination and sluggish water oxidation kinetics. While numerous strategies, namely, elemental doping, morphology engineering, heterojunction formation, and catalyst modification, have been extensively explored to enhance the PEC performance, the application of external magnetic fields (MFs) to affect the catalysis or charge carrier dynamics remains yet to be exploited. Herein, BiVO 4 is first selected as a representative photoanode, demonstrating that an ultrathin ferromagnetic coating based on Fe 2 TiO 5 , when combined with an external MF, boosts its solar water oxidation performance. The combined analyses of the charge transfer and separation efficiency together with ultraviolet photoelectron spectroscopy and transient absorption spectroscopy data revealed that the MF positively affects the band alignment across the BiVO 4 /Fe 2 TiO 5 interface, improving the charge separation, while the oxygen evolution at the Fe 2 TiO 5 /electrolyte interface was promoted. Finally, we expand this concept to other metal oxide photoanodes, such as TiO 2 , WO 3 , and Fe 2 O 3 , demonstrating the universality of such an approach. Overall, this work pioneers a novel route to harvest external MFs and improve the PEC response of common nonmagnetic semiconductor photoelectrodes in photoelectrocatalytic conversion.

The present study aimed to analyze notifications of intimate partner violence (IPV) against indigenous women in the macro-region of Dourados-MS, Brazil, from 2009 to 2020. This is a cross-sectional study with secondary data from registered reports in the Notifiable Diseases Information System (SINAN) of indigenous women who suffered violence. Descriptive statistics of the variables and Poisson regression were performed to determine the prevalence ratio (PR). IPV represented 56.6% of reports. The most reported types of violence were physical violence (93.3%) and psychological violence (27%). In the adjusted analysis, IPV was associated with women with partners (PR 1.32, 95%CI 1.19; 1.46), and women in situations of repeated violence (PR 1.15, 95%CI 1.05; 1.25) and at home as the place of occurrence (PR 1.13, 95%CI 1.01; 1.29). The majority of reports of violence against indigenous women registered in the Dourados health macro-region were perpetrated by an intimate partner. Knowledge of the profile of violence that arrives at health services, combined with associated factors, should enable the implementation of strategies aimed at reducing the number of cases.

This study aimed to analyze the adaptation of prenatal care offered to Indigenous women and its association with maternal characteristics and health services. This is a cross-sectional study, conducted with 461 Indigenous women who gave birth and/or received immediate postpartum care in the municipalities of Mato Grosso do Sul, between 2021 and 2022. An indicator of minimum prenatal adequacy was developed, which was classified as adequate when the woman started prenatal care in the 1st trimester of pregnancy, had ≥7 consultations, and had routine exams recorded. Logistic regression models were used to estimate the adjusted odds ratios and factors associated with prenatal adequacy. It was found that 67.2% began prenatal care in the 1st trimester, 51.8% had ≥7 consultations, and 40.6% had exam results recorded. About 1 in 4 Indigenous women achieved the proposed adequacy; the associated maternal characteristics were ethnicity, region of residence, and place of residence. Prenatal care revealed health inequities, with low adequacy rates in prenatal care and worse rates among women living in villages and settlements in the southern region of the state.

Background: Despite nearly 100% 5-year survival for localised prostate cancer, the survival rate for metastatic prostate cancer significantly declines to 32%. Thus, it is crucial to identify molecular indicators that reflect the progression from localised disease to metastatic prostate cancer., Methods: To search for molecular indicators associated with prostate cancer metastasis, we performed proteomic analysis of rapid autopsy tissue samples from metastatic prostate cancer (N = 8) and localised prostate cancer (N = 2). Then, we utilised multiple independent, publicly available prostate cancer patient datasets to select candidates that also correlate with worse prostate cancer clinical prognosis., Results: We identified 154 proteins with increased expressions in metastases relative to localised prostate cancer through proteomic analysis. From the subset of these candidates that correlate with prostate cancer recurrence (N = 28) and shorter disease-free survival (N = 37), we identified a 5-gene signature panel with improved performance in predicting worse clinical prognosis relative to individual candidates., Conclusions: Our study presents a new 5-gene signature panel that is associated with worse clinical prognosis and is elevated in prostate cancer metastasis on both protein and mRNA levels. Our 5-gene signature panel represents a potential modality for the prediction of prostate cancer progression towards the onset of metastasis., Competing Interests: Competing interests: JRW is founder and owner of Resphera Biosciences LLC. Ethics approval and consent to participate: All patient samples collected through the rapid autopsy programme were approved by the Institutional Review Board of the University of Michigan, as described previously in Shah et al. [13]. All methods were performed in accordance with the ethical guidelines and relevant regulations from the Regional Ethics Committee. Consent for publication: All authors have given read and given their approval for publication., (© 2024. The Author(s).)

Purpose: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP ND ) in rodent PET studies., Procedures: PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([ 18 F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BP ND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT., Results: The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BP ND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter., Conclusions: The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BP ND in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners., Competing Interests: Declarations. Ethical approval: All experimental protocols and procedures used in this study were reviewed and approved by the Johns Hopkins School of Medicine Animal Care and Use Committee. Consent for publication: Not indicated., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Purpose: Mutational data from multiple solid and liquid biospecimens of a single patient is often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence., Experimental Design: Utilizing 8,000 patient tumors from The Cancer Genome Atlas (TCGA) across 33 cancer types, we estimated background rates of co-occurrence rates of mutations between discrete pairs of samples across cancers and by cancer type. We developed a mutational profile similarity score (MPS) that uses a large background database to produce confidence estimates that two tumors share a unique, related molecular profile. The MPS algorithm was applied to randomly paired tumor profiles, including patients who underwent repeat solid tumor biopsies sequenced with MSK-IMPACT (n=53,113). We also evaluated the MPS in sample pairs from single patients with multiple cancers (n=2,012), as well as patients with plasma and solid-tumor variant profiles (n=884 patients)., Results: In unrelated tumors, nucleotide-specific variants are shared in 1.3% (cancer-type agnostic) and in 10-13% (cancer-type specific) of cases. The mutational profile similarity (MPS) method contextualized shared variants to specify whether patients had a single cancer versus multiple distinct cancers. When multiple tumors were compared from the same patient, and an initial clinicopathologic diagnosis was discordant with molecular findings, the MPS anticipated future diagnosis changes in 28% of examined cases., Conclusions: Use of a novel shared variant framework can provide information to clarify the molecular relationship between compared biospecimens with minimal required input.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights., Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure., Study Design: Cohort study; Level of evidence, 3., Methods: The authors prospectively recruited patients undergoing rACLR from the MARS cohort and obtained preoperative radiographs, surgeon-reported intraoperative findings, and 2- and 6-year follow-up data on patient-reported outcomes, additional surgeries, and graft failure. Machine learning models including logistic regression (LR), XGBoost, gradient boosting (GB), random forest (RF), and a validated ensemble algorithm (AutoPrognosis) were built to predict graft failure by 6 years postoperatively. Validated performance metrics and feature importance measures were used to evaluate model performance., Results: The cohort included 960 patients who completed 6-year follow-up, with 5.7% (n = 55) experiencing graft failure. AutoPrognosis demonstrated the highest discriminative power (model area under the receiver operating characteristic curve: AutoPrognosis, 0.703; RF, 0.618; GB, 0.660; XGBoost, 0.680; LR, 0.592), with well-calibrated scores (model Brier score: AutoPrognosis, 0.053; RF, 0.054; GB, 0.057; XGBoost, 0.058; LR, 0.111). The most important features for AutoPrognosis model performance were prior compromised femoral and tibial tunnels (placement and size) and allograft graft type used in current rACLR., Conclusion: The present study demonstrated the ability of the novel AutoPrognosis machine learning model to best predict the risk of graft failure in patients undergoing rACLR at 6 years postoperatively with moderate predictive ability. Femoral and tibial tunnel size and position in prior ACLR and allograft use in current rACLR were all risk factors for rACLR failure in the context of the AutoPrognosis model. This study describes a unique model that can be externally validated with larger data sets and contribute toward the creation of a robust rACLR bedside risk calculator in future studies., Registration: NCT00625885 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 5R01-AR060846). See Supplemental Material for individual disclosures. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Wesselsbron virus (WSLV) is a neglected mosquito-borne virus within the yellow fever subgroup in the genus Orthoflavivirus of the Flaviviridae family. Despite being primarily a veterinary pathogen able to cause stillbirths, congenital malformations, and mortality in ruminants, WSLV also infects humans, causing a usually self-limiting febrile illness, or may lead to neurological complications in rare cases. WSLV causes sporadic outbreaks in Southern Africa, but findings in mosquitoes from other African countries suggest a wider distribution. Here, we report the detection and isolation of WSLV from an Aedes mcintoshi mosquito collected in a pristine ecosystem within Semuliki National Park, western Uganda. The detected strain M5937-UG-2018 was impaired in infectivity, replication, and production of infectious particles in cell lines derived from different hosts compared to an epidemic reference strain, SA H177. Full-genome sequencing by next-generation sequencing from the mosquito homogenate revealed a maximum nucleotide identity of 98.1% to a WSLV isolate from a human sample collected in South Africa in 1996. M5937-UG-2018 grouped in phylogenetic analyses with strains from South Africa and Senegal. Reconstruction of the temporal and spatial dispersal of WSLV across Africa estimated a likely origin of WSLV in South Africa in the early 19th century and spread in Southern Africa in the following decades. Long-distance movement toward Western and Eastern Africa was modeled to have occurred in the early 21st century. However, displacing the origin of M5937-UG-2018 did not decrease the likelihood of the model supporting the hypothesis that WSLV is widely distributed in Africa.IMPORTANCEWSLV is a neglected mosquito-borne virus causing teratogenicity in ruminants and febrile illness in humans. WSLV is mainly endemic to Southern Africa, but findings in other regions suggest a wider distribution on the continent. Knowledge of the distribution of WSLV is impaired as differential diagnostics are rarely performed in livestock and humans presenting with symptoms compatible with WSLV infection. Our work investigating viral infections in mosquitoes from a remote tropical rainforest region demonstrates that WSLV is endemic in Uganda. The isolated virus was less infective and showed lower replication ability in vitro compared to an epidemic isolate from South Africa. Phylogeographic reconstruction of spatial and temporal movements, along with the displacement of the origin of the newly detected strain , suggests that WSLV may be widely distributed across Africa. Our data show that the geographic distribution of WSLV and its impact on human and animal health are likely underestimated.

Background: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks., Methods: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement., Results: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research., Conclusions: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care., Competing Interests: Competing interests: EA: grants from Swiss Academy for Anesthesia Research, Bbraun, Swiss National Science Foundation. Honoraria from Bbraun and Sintetica. JG: consulting fees from Pacira Biosciences and Pajunk Medical. AP: honoraria from FuijiFilm Sonosite. MW: advisory Board for Sintetica, Honoraria from Wisonic and Medovate. SA: Advisory Panel for DATAR innovations. JA: moderator of the Working Group Regional Anaesthesia Switzerland, Honoraria from Medtronic and Sintetica. AMRA: honoraria form AllerganSébastien Bloc—Consulting fees from BBraun—GE Medical Systems—Pajunk—Pfizer SAS. JB: Consulting fees from Intelligent Ultrasound. BC: jonoraria from Bbraun and Rivanna, Consulting from Stryker and Flat Medical, Research funding from Pacira, Share Options from Flat Medical. AC: speaking honoraria from GE Healthcare, royalties from textbook Oxford University Press. SC: consulting fees from MSD, Bbraun Medical, Wisonic, research grants from BARA (Belgian association of Regional anesthesia), ESRA and BeSARP (Belgian anesthesia society) HE-Consulting/Advisory Board Neuronoff, SPR, GateScience, NeuronoffBenjamin Fox—Speaking fees from Medovate and Sintetica. SG: consulting and speaking fees from MSD Switzerland. PH: royalties from Bestek Products. NH: Honoraria from Butterfly Network. RMGH- Honoraria from GE Healthcare. MH: consulting fees from Pacira Biosciences, Honoraria from Parcira Biosciences and Pajunk Medical. BMI: research funding to institution from SPR Therapeutics, Infutronix, Epimed International. AM: Consultant fees from Intelligent Ultrasound. CM: consultant fees from Masimo Corporation. SGM: Owner SGM Consulting, Partner Parvizi Surgical Innovations, Patent for Multicatheter infusion system. AN: Research support from SPR Therapeutics. SLO: Royalties from book Wolters-Kluwer. APawa: Honoraria from GE Healthcare, Consulting fees from Pacira Biosciences. PP: equipment support from Sonosiite Fujifilm Canada. MPS: Medovate speaking but no honoraria paid. SKS- Cofounder of Gate Science (developing a catheter for performing nerve blocks) JS: consulting fees from Sintetica. RT: Consulting fees from Clarius Mobile Health. VU: Associate Editor of the Canadian Journal of Anesthesia and Regional Anesthesia & Pain Medicine journals. TV: honoraria from CSL Behring, Pajunk., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown., Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery., Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P ≤ .04)., Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients' odds of having a significantly better 6-year clinical outcome in this cohort., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was funded by grant No. 5R01-AR060846 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. All author disclosures are listed in the Appendix (available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Leptin is a homeostatic regulatory element that signals the presence of adipocyte energy stores, reduces food intake, and increases energy expenditure. Similarly, serotonin (5-HT), a signaling molecule found in both the central and peripheral nervous systems, also controls food intake. Using neuronal tract tracing, pharmacologic and optogenetic approaches, and in vivo microdialysis, combined with behavioral end points, we tested the hypothesis that leptin controls food intake not only by activating hypothalamic leptin receptors (LepRs) but also through activation of LepRs expressed by serotonergic raphe neurons that send projections to the arcuate (ARC). We showed that microinjection of leptin directly into the dorsal raphe nucleus (DRN) reduced food intake in rats. This effect was mediated by LepR-expressing neurons in the DRN, because selective optogenetic activation of these neurons at either their DRN cell bodies or their ARC terminals reduced food intake. Anatomically, we identified a unique population of serotonergic raphe neurons expressing LepRs that send projections to the ARC. Finally, by using in vivo microdialysis, we showed that leptin administration to the DRN increased 5-HT efflux into the ARC, and specific antagonism of the 5-HT2C receptors in the ARC diminished the leptin anorectic effect. Overall, this study identified a novel circuit for leptin-mediated control of food intake through a DRN-ARC pathway, identifying a new level of interaction between leptin and serotonin to control food intake. Characterization of this new pathway creates opportunities for understanding how the brain controls eating behavior and opens alternative routes for the treatment of eating disorders., (© 2024 by the American Diabetes Association.)

Social prescribing has become a global phenomenon. A Delphi study was recently conducted with 48 social prescribing experts from 26 countries to establish global agreement on the definition of social prescribing. We reflect on the use and utility of the outputs of this work, and where we go from here., (© 2024. The Author(s).)

The use of low-cost sensors, with open-source code, facilitates greater spatial resolution and flexibility of environmental monitoring, thus generating more information and overcoming limitations of traditional commercial sensors. Measurement of water turbidity using submerged sensors can be problematic in that rapid biofouling requires frequent site visits to remove, clean, calibrate and replace the sensor. We therefore designed an automated system using low-cost commercially-available sensors that pumps water from the stream, samples it for turbidity and purges remaining water, leaving the turbidity sensor dry between measurements, thus greatly reducing the biofouling problem and minimizing operation costs. Our station was able to estimate suspended sediment concentrations between 0 and 6 g/L with a root mean square error (RMSE) around 5 % of the total range, which meets typical research and operational study requirements. The results showed that the monitoring station is capable of monitoring water level and turbidity for long periods without the need of cleaning the turbidity sensor, due to its purge function. We demonstrated that spatially intense measurement of turbidity within catchments and drainage networks can be achieved at a relatively low cost, which allows a better understanding of the main sources of suspended sediments and their spatial and temporal variability., 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., (© 2024 The Author(s).)

Devulcanized rubber could be a valuable material feedstock to help in the manufacture of sustainable rubber products. However, the differences in the chemistry and structure of devulcanized rubber have limited industrial uptake. This work demonstrates how devulcanization affects the concentration and ratios of mono-, di-, and polysulfidic cross-links. These residual cross-links make devulcanized rubber chemically dissimilar from virgin rubber, affecting (re)vulcanization. The hypothesis that the sulfur rank of revulcanized material can be modified by the sulfur/accelerator ratio was evaluated by two different cure packages. Despite substantial differences in the accelerator/sulfur ratio, both recycled rubber compounds favored the formation of polysulfidic cross-links., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short-term inflammation-mediated outcomes after cardiac surgery. The impact of CH on long-term postoperative outcomes remains unknown., Methods and Results: In this cohort study, patients undergoing elective cardiac surgery were included from January 2017 to September 2019. Patients were screened for CH using a predefined gene panel of 19 genes. Recorded clinical events were all-cause death, major adverse cardiac and cerebral events including cardiovascular death, myocardial infarction or nonscheduled coronary revascularization, stroke, and hospitalization for acute heart failure. The primary study outcome was time to a composite criterion including all-cause mortality and major adverse cardiac and cerebral events. Among 314 genotyped patients (median age: 67 years; interquartile range 59-74 years), 139 (44%) presented with CH, based on a variant allelic frequency ≥1%. Carriers of CH had a higher proportion of patients with a history of atrial fibrillation (26% for CH versus 17% for non-CH carriers, P =0.022). The most frequently mutated genes were DNMT3A , TET2 , and ASXL1 . After a median follow-up of 1203 [813-1435] days, the primary outcome occurred in 50 patients. After multivariable adjustment, CH was independently associated with a higher risk for the primary outcome (hazard ratio, 1.88 [95% CI, 1.05-3.41], P =0.035). Most adverse events occurred in patients carrying TET2 variants., Conclusions: In patients undergoing cardiac surgery, CH is frequent and associated with a 2-fold increased long-term risk for major adverse clinical outcomes. CH is a novel risk factor for long-term postcardiac surgery complications and might be useful to personalize management decisions., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03376165.

We introduce metaMDBG, a metagenomics assembler for PacBio HiFi reads. MetaMDBG combines a de Bruijn graph assembly in a minimizer space with an iterative assembly over sequences of minimizers to address variations in genome coverage depth and an abundance-based filtering strategy to simplify strain complexity. For complex communities, we obtained up to twice as many high-quality circularized prokaryotic metagenome-assembled genomes as existing methods and had better recovery of viruses and plasmids., (© 2024. The Author(s).)

Background and Purpose: Optimal clinical outcome with successful recanalization from endovascular thrombectomy (EVT) requires optimal blood pressure (BP) management. We aimed to evaluate the efficacy and safety of the intensive BP target (< 140 mm Hg) versus the standard BP target (< 180 mm Hg) after EVT for acute ischemic stroke., Methods: We conducted a systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 7th, 2023. We used the fixed-effect model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI)., Prospero Id: CRD42023463206., Results: We included four RCTs with 1559 patients. There was no difference between intensive BP and standard BP targets regarding the National Institutes of Health Stroke Scale (NIHSS) change after 24 h [MD: 0.44 with 95% CI (0.0, 0.87), P = 0.05]. However, the intensive BP target was significantly associated with a decreased risk of excellent neurological recovery (mRS ≤ 1) [RR: 0.87 with 95% CI (0.76, 0.99), P = 0.03], functional independence (mRS ≤ 2) [RR: 0.81 with 95% CI (0.73, 0.90), P = 0.0001] and independent ambulation (mRS ≤ 3) [RR: 0.85 with 95% CI (0.79, 0.92), P < 0.0001]., Conclusions: An intensive BP target after EVT is associated with worse neurological recovery and significantly decreased rates of functional independence and independent ambulation compared to the standard BP target. Therefore, the intensive BP target should be avoided after EVT for acute ischemic stroke., (© 2024. The Author(s).)

Although free-floating thrombus (FFT) poses a significant risk of stroke or transient ischemic attack (TIA), optimal management strategies are uncertain. To determine the state-of-the-art of medical interventions for FFT, we conducted a systematic review of the efficacy of various medical interventions and factors influencing FFT resolution and recurrence. A comprehensive search of Embase, PubMed, and ScienceDirect identified 61 studies encompassing 179 patients with FFT-related stroke or TIA treated with anticoagulants, antiplatelets, or their combinations. Primary outcomes assessed were stroke recurrence and thrombus resolution. Statistical analyses (Fisher's exact test, chi-square test, Mann-Whitney test, and Kruskal-Wallis test) utilized significance set at p < 0.05. Over a median follow-up of 7 months, thrombus resolution occurred in 65% of patients, while 11.2% experienced recurrence, primarily as TIAs. Cardioembolism was significantly less common in resolved cases ( p = 0.025). Combination therapy (antiplatelets, anticoagulants, and statins) significantly enhanced clot resolution (OR 11.4; 95% CI 1.436-91.91; p = 0.021) compared to monotherapies. Ulcerated plaque was a significant predictor of recurrence (OR 8.2; 95% CI 1.02-66.07; p = 0.048). These findings underscore the superiority of combination therapy in FFT management and highlight the need for targeted interventions in patients with ulcerated plaques to mitigate recurrence risk.

Photoelectrochemical (PEC) devices offer a promising platform toward direct solar light harvesting and chemical storage through artificial photosynthesis. However, most prototypes employ wide bandgap semiconductors, moisture-sensitive inorganic light absorbers, or corrosive electrolytes. Here, the design and assembly of PEC devices based on an organic donor-acceptor bulk heterojunction (BHJ) using a carbon-based encapsulant are introduced, which demonstrate long-term H 2 evolution and CO 2 reduction in benign aqueous media. Accordingly, PCE10:EH-IDTBR photocathodes display long-term H 2 production for 300 h in a near-neutral pH solution, whereas photocathodes with a molecular CO 2 reduction catalyst attain a CO:H 2 selectivity of 5.41±0.53 under 0.1 sun irradiation. Their early onset potential enables the construction of tandem PCE10:EH-IDTBR - BiVO 4 artificial leaves, which couple unassisted syngas production with O 2 evolution in a reactor completely powered by sunlight, sustaining a 1:1 ratio of CO to H 2 over 96 h of operation., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Molybdenum sulfide (MoS 2 ) and modified MoS 2 with different percentages of CdS (10%, 30%, and 50% CdS@MoS 2 ) were successfully synthesized and characterized. The photocatalytic performance of the MoS 2 and CdS@MoS 2 was evaluated by degrading brilliant green (BG), methylene blue (MB), and rhodamine B (RhB) dyes under visible light irradiation. Amongst the synthesized photocatalysts, 50% CdS@MoS 2 exhibited the highest photocatalytic activity, degrading 97.6%, 90.3%, and 75.5% of BG, MB, and RhB dyes, respectively within 5 h. The active species involved in the degradation processes were investigated. All trapping agents inhibited BG and MB degradation to a similar extent, indicating that all of the probed active species play an important role in the degradation of BG and MB. In contrast, h + and O 2 •- were found to be the main reactive species in the photocatalytic RhB degradation. A potential mechanism for the photocatalytic degradation of dyes using CdS@MoS 2 has been proposed. This work highlights the potential of CdS@MoS 2 as a photocatalyst for more efficient water remediation applications., (© 2024. The Author(s).)

Copper indium sulfide (CuInS 2 ) exhibits strong visible light absorption and thus has the potential for good photocatalytic activity; however, rapid charge recombination limits its practical usage. An intriguing strategy to overcome this issue is to couple CuInS 2 with another semiconductor to form a heterojunction, which can improve the charge carrier separation and, hence, enhance the photocatalytic activity. In this study, photocatalysts comprising CuInS 2 with a secondary CuS phase (termed CuIn x S y ) and CuIn x S y loaded with ZnS (termed ZnS@CuIn x S y ) were synthesized via a microwave-assisted method. Structural and morphological characterization revealed that the ZnS@CuIn x S y photocatalyst comprised tetragonal CuInS 2 containing a secondary phase of hexagonal CuS, coupled with hexagonal ZnS. The effective band gap energy of CuIn x S y was widened from 2.23 to 2.71 as the ZnS loading increased from 0 to 30%. The coupling of CuIn x S y with ZnS leads to long-lived charge carriers and efficient visible-light harvesting properties, which in turn lead to a remarkably high activity for the photocatalytic degradation of brilliant green (95.6% in 5 h) and conversion of 4-nitrophenol to 4-nitrophenolate ions (95.4% in 5 h). The active species involved in these photocatalytic processes were evaluated using suitable trapping agents. Based on the obtained results, photocatalytic mechanisms are proposed that emphasize the importance of h + , O 2 •- , and OH - in photocatalytic processes using ZnS@CuIn x S y ., (© 2024. The Author(s).)

Quantifying pollutant removal by stormwater wetlands requires intensive sampling which is cost-prohibitive for authorities responsible for a large number of wetlands. Wetland managers require simple indicators that provide a practical means of estimating performance and prioritising maintenance works across their asset base. We therefore aimed to develop vegetation cover and metrics derived from monitoring water level, as simple indicators of likely nutrient pollutant removal from stormwater wetlands. Over a two-year period, we measured vegetation cover and water levels at 17 wetlands and used both to predict nitrogen (N) and phosphorus (P) removal. Vegetation cover explained 48 % of variation in total nitrogen (TN) removal; with a linear relationship suggesting an approximate 9 % loss in TN removal per 10 % decrease in vegetation cover. Vegetation cover is therefore a useful indicator of TN removal. Further development of remotely-sensed data on vegetation configuration, species and condition will likely improve the accuracy of TN removal estimates. Total phosphorus (TP) removal was not predicted by vegetation cover, but was weakly related to the median water level which explained 25 % of variation TP removal. Despite weak prediction of TP removal, metrics derived from water level sensors identified faults such as excessive inflow and inefficient outflow, which in combination explained 50 % of the variation in the median water level. Monitoring water levels therefore has the potential to detect faults prior to loss of vegetation cover and therefore TN removal, as well as inform the corrective action required., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Little is known about the impact of an ecological dynamics (ED) intervention (EDI) on primary school children's physical literacy and well-being in the Hong Kong context. The aim of this project is to introduce a physical literacy and well-being framework through an EDI that allows primary school children to develop good physical activity (PA) and daily behavioural habits., Methods and Analysis: A four-arm (cluster) randomised controlled trial will be conducted to examine the effect of EDI on physical literacy and well-being in primary schools located in each of the 18 administrative districts of Hong Kong. Four classes in senior primary students (grade 4) at each school will be randomly assigned to the four different conditions. These participating schools will be equipped with sit-stand desks, PA recess facility and equipment, and sleep pillows. The research team will adopt both objective measures (aerobic fitness, fundamental movement skills, daily behaviour-physical activity and cognitive function) and self-reported measures (perceived physical literacy, quality of life, sleep quality) covering the elements and domains of physical literacy and well-being to examine the effects of EDIs at four time points, including baseline assessment, 3 months after intervention, postintervention and 3-month follow-up assessment. One-way analyses of variance (ANOVAs) will be used to test for differences in the baseline characteristics of participants between groups. Repeated measure ANOVAs and MANCOVA, with time (baseline, after intervention and follow-up) as within-subjects factor, and intervention group as between-subjects factors, will be used to evaluate the effects of different interventions on the students' physical literacy and well-being. A Bonferonni correction to the p value will be calculated to adjust for multiple tests., Ethics and Dissemination: Ethical approval was sought from the Joint CUHK-NTEC Clinical Research Ethics Committee in Hong Kong (CREC Ref.No.:2024.027). The finding of this study will be disseminated via peer-reviewed journals, international conference presentations and academic lectures. For secondary analysis of the data, please contact the corresponding author for permission., Trial Registration Number: ISRCTN84025914., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Kimberley region of Western Australia (WA) is classified by the Modified Monash Model as MM6 & 7 ('Remote/Very Remote'). Many physiotherapists in the Kimberley are considered 'rural generalists' and require a diverse set of clinical and non-clinical skills to work successfully within this setting., Objective: To understand physiotherapists' perspectives regarding job satisfaction within the Kimberley region a 'rural and remote' areas of Australia., Design: An exploratory case study approach examined physiotherapists' job satisfaction in the Kimberley. Each participant completed a demographic survey and a one-on-one face-to-face interview lasting for approximately 60 minutes. Transcriptions were analysed and presented thematically. Eleven physiotherapists (nine women, two men, median age = 32 [27-60] years) participated in the study. Participants' median time working in the Kimberley was 2 (1-15) years; eight participants completed a rural placement, and eight participants had a rural background., Findings and Discussion: Two overarching themes relating to job satisfaction emerged: 'personal factors' and 'workplace factors'. Furthermore, several sub-themes illustrated high levels of job satisfaction. Positive sub-themes relating to personal factors included 'belonging to the community and a rural lifestyle'. 'Diversity in caseloads' and 'workplace culture' were examples of positive workplace sub-themes. Subthemes that challenged the participants personally were 'family arrangements' including schooling, 'spousal employment and family separation' and the 'transiency and social issues' within these remote communities. Workplace challenges comprised of 'barriers to providing best practice' and the 'workforce and clinical experience' found within the Kimberley physiotherapy community and the wider health care workforce. The primary challenge of job satisfaction that encompassed both personal and workplace factors was 'accommodation', with 'cost', 'lack of availability', and 'perceived unsafe location' challenging physiotherapists' decisions to remain in the Kimberley., Conclusion: This study describes the many factors impacting job satisfaction among physiotherapists in a rural and remote location in WA Australia. These factors warrant consideration by organisations interested in improving recruitment and retention in this context. Improving recruitment and retention in physiotherapists in rural and remote Australia has the potential to positively influence health service provision, and therefore improve health outcomes for those living in rural and remote communities., (© 2024 National Rural Health Alliance Ltd.)

Our knowledge of alphavirus genetic diversity is mainly based on viruses isolated from anthropophilic mosquito species, humans, and livestock during outbreaks. Studies on alphaviruses from sylvatic amplification cycles in sub-Saharan Africa have been conducted less often than from epizootic environments. To gain insight into alphavirus diversity in enzootic transmission cycles, we collected over 23,000 mosquitoes in lowland rainforest and savannah gallery forest in southwestern Uganda and tested them for alphavirus infections. We detected Sindbis virus (SINV) in a Culex Culex sp. mosquito and Middelburg virus (MIDV) in Eretmapodites intermedius and Mansonia africana . MIDV is a mosquito-borne alphavirus that causes febrile illness in sheep, goats, and horses and was previously not known to occur in Uganda. SINV, also a mosquito-borne alphavirus, causes mild infections in humans. Full genomes of SINV and MIDV were sequenced, showing a nucleotide identity of 99% to related strains. Both isolates replicated to high titres in a wide variety of vertebrate cells. Our data suggest endemic circulation of SINV and MIDV in Uganda., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Graff, Eibner, Ochieng, Jones, Nsubuga, Lutwama, Rwego and Junglen.)

Objective: To analyze the temporal trend of completeness and consistency of data on notifications of violence against indigenous women in the health macro-region of Dourados, state of Mato Grosso do Sul, Brazil, between 2009 and 2020., Methods: An ecological time series study was conducted using data from the Notifiable Health Conditions Information System; Prais-Winsten regression was used to analyze the trend of data completeness and consistency, as well as the proportion of completed and coherent fields., Results: A total of 2,630 cases were reported; completeness was found to be very poor in the variable "occupation" (48.9%) and poor in the variables "schooling" (68.3%) and "time of occurrence" (67.9%); in the analysis of temporal trends, only the variable "occupation" showed a decreasing trend (p = 0.045)., Conclusion: The data analyzed demonstrated the need for improvement in the completeness of the variables "schooling", "occupation" and "time of occurrence" of the violent act., Main Results: There was a progressive increase in notifications over the years. Most of the variables showed regular or excellent completeness and consistency. In the analysis of temporal trend, only the "occupation" variable showed a decreasing trend., Implications for Services: Care for victims of violence is part of the daily routine of health services, and it is essential for health professionals to provide adequate compulsory notification for a comprehensive understanding of the victims' profile, thus assisting in addressing this issue., Perspectives: Further studies are needed to understand the factors associated with violence against indigenous women, which could help the development of health promotion actions and violence prevention strategies targeting these women.

Optical coherence tomography angiography (OCTA) is widely used for non-invasive retinal vascular imaging, but the OCTA methods used to assess retinal perfusion vary. We evaluated the different methods used to assess retinal perfusion between OCTA studies. MEDLINE and Embase were searched from 2014 to August 2021. We included prospective studies including ≥ 50 participants using OCTA to assess retinal perfusion in either global retinal or systemic disorders. Risk of bias was assessed using the National Institute of Health quality assessment tool for observational cohort and cross-sectional studies. Heterogeneity of data was assessed by Q statistics, Chi-square test, and I 2  index. Of the 5974 studies identified, 191 studies were included in this evaluation. The selected studies employed seven OCTA devices, six macula volume dimensions, four macula subregions, nine perfusion analyses, and five vessel layer definitions, totalling 197 distinct methods of assessing macula perfusion and over 7000 possible combinations. Meta-analysis was performed on 88 studies reporting vessel density and foveal avascular zone area, showing lower retinal perfusion in patients with diabetes mellitus than in healthy controls, but with high heterogeneity. Heterogeneity was lowest and reported vascular effects strongest in superficial capillary plexus assessments. Systematic review of OCTA studies revealed massive heterogeneity in the methods employed to assess retinal perfusion, supporting calls for standardisation of methodology., (© 2024. Crown.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Although several antithrombotic strategies have been investigated for the management of cryptogenic strokes, ie, ischemic strokes without known etiologies, an optimal antithrombotic strategy for cryptogenic strokes is unknown. We aim to assess oral antithrombotic agents' comparative efficacy and safety after cryptogenic stroke to identify an optimal treatment.A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and Web of Science until February 2024. We used the random-effects model to report dichotomous outcomes using a risk ratio (RR) with a 95% confidence interval (CI). Frequentist network meta-analysis was conducted using R, version 4.3.1.Seven RCTs with 15,240 patients were included. None of the OACs showed a significant efficacy in preventing all-cause mortality, stroke recurrence, cardiovascular mortality, and major adverse cardiac events compared to aspirin. Also, safety measures were similar between different OACs and aspirin regarding safety measures, including major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]).There was no difference between various OACs and aspirin regarding efficacy and safety outcomes. There is a greater risk of major bleeding with rivaroxaban. Further research is still warranted to define a personalized strategy for selecting antithrombotic strategies after cryptogenic stroke on a case-by-case basis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Istaroxime, an intravenous inotropic agent with a dual mechanism-increasing both cardiomyocyte contractility and relaxation-is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model-according to heterogeneity-to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m 2 ) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: -0.39, 95% CI: -0.58, -0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: -3.05, 95% CI: -5.27, -0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.

Background: The Discharge Medicines Review (DMR) is a community pharmacy service in Wales that aims to reduce medicines-related harm after care transitions, including hospital discharge. To undertake a DMR, the Community Pharmacist must receive a patient's discharge medicines information, either electronically, by fax or presented by the patient. Although the DMR has evidenced benefits for improving patient safety, its evaluation showed inconsistent uptake, which Community Pharmacists partially attributed to hospitals not providing the necessary information., Objective: Aiming to develop recommendations to improve hospital engagement to DMR referrals, this study explores hospital pharmacy professionals' views of the service., Methods: Qualitative focus groups, using hermeneutic phenomenology, were conducted in 16 hospitals across Wales, using a quota sampling method to include 61 Pharmacists and 31 Pharmacy Technicians. To understand the suboptimal engagement to DMR referrals, framework analysis was undertaken using the Consolidated Framework for Implementation Research (CFIR)., Results: The data were mapped onto all five CFIR domains, each containing barriers and facilitators to engagement with DMR referrals and suggestions for improvement. Only one hospital had successfully implemented DMR referrals, with many participants lacking any knowledge of the service or how to refer to it. Specific barriers included a clear absence of processes to implement referrals and engage hospital pharmacy professionals. A considerable barrier was many participants' perceptions that Community Pharmacist roles were less clinically orientated and patient-centred than their own, viewing them almost as a different profession. Participants believed that local champions for DMR referrals could promote engagement and integrate them into the workflow of hospital pharmacy professionals. Further recommendations to improve engagement was staff training for DMRs and regular feedback of its value., Conclusion: Policymakers may use the findings and recommendations from this study to promote hospital pharmacy staff engagement to similar community pharmacy services like the Discharge Medicines Service in England., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Wearable sensors provide a tool for at-home monitoring of motor impairment progression in neurological conditions such as Parkinson's disease (PD). This study examined the ability of deep learning approaches to grade the motor impairment severity in a modified version of the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) using low-cost wearable sensors. We hypothesized that expanding training datasets with motion data from healthy older adults (HOAs) and initializing classifiers with weights learned from unsupervised pre-training would lead to an improvement in performance when classifying lower vs. higher motor impairment relative to a baseline deep learning model (XceptionTime). This study evaluated the change in classification performance after using expanded training datasets with HOAs and transferring weights from unsupervised pre-training compared to a baseline deep learning model (XceptionTime) using both upper extremity (finger tapping, hand movements, and pronation-supination movements of the hands) and lower extremity (toe tapping and leg agility) tasks consistent with the MDS-UPDRS. Overall, we found a 12.2% improvement in accuracy after expanding the training dataset and pre-training using max-vote inference on hand movement tasks. Moreover, we found that the classification performance improves for every task except toe tapping after the addition of HOA training data. These findings suggest that learning from HOA motion data can implicitly improve the representations of PD motion data for the purposes of motor impairment classification. Further, our results suggest that unsupervised pre-training can improve the performance of motor impairment classifiers without any additional annotated PD data, which may provide a viable solution for a widely deployable telemedicine solution.

Climate change and air pollution are closely interlinked since carbon dioxide and air pollutants are co-emitted from fossil fuel combustion. Net Zero (NZ) policies aiming to reduce carbon emissions will likely bring co-benefits in air quality and associated health. However, it is unknown whether regional NZ policies alone will be sufficient to reduce air pollutant levels to meet the latest 2021 World Health Organisation (WHO) guidelines. Here, we carried out high resolution air quality modelling for in the West Midlands region, a typical metropolitan area in the UK, to quantify the effects of different NZ policies on air quality. Results show that NZ policies will significantly improve air quality in the West Midlands, with up to 6 μg m -3 (21%) reduction in annual mean NO 2 (mostly through the electrification of vehicle fleet, EV) and up to 1.4 μg m -3 (12%) reduction in annual mean PM 2.5 projected for 2030 relative to levels under a "business as usual" (BAU) scenario. Under BAU, 2030 PM 2.5 concentrations in most wards would be below 10 μg m -3 whilst under the Net Zero scenario, those in all wards would be below 10 μg m -3 . This means that the ward averages in the West Midlands would meet the UK PM 2.5 of 10 μg m -3 target a decade early under the Net Zero scenario. However, no ward-level-averaged annual mean PM 2. concentrations meet the 2021 WHO Air Quality guideline level of 5 μg m -3 under any scenario. Similarly for NO 2 only 18 wards (8% of the region's population) are predicted to have NO 2 concentrations below the 2021 WHO guideline level (10 μg m -3 ). Decarbonisation policies linked to Net Zero deliver substantial regional air quality benefits, but are not in isolation sufficient to deliver clean air with air pollutant levels low enough to meet the 2021 WHO guidelines., 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., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Children with beta-thalassemia (BT) present with an increase in carotid intima-medial thickness, an early sign suggestive of premature atherosclerosis. However, it is unknown if there is a direct relationship between BT and atherosclerotic disease. To evaluate this, wild-type (WT, littermates) and BT (Hbb th3/+ ) mice, both male and female, were placed on a 3-mo high-fat diet with low-density lipoprotein receptor suppression via overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation (D377Y). Mechanistically, we hypothesize that heme-mediated oxidative stress creates a proatherogenic environment in BT because BT is a hemolytic anemia that has increased free heme and exhausted hemopexin, heme's endogenous scavenger, in the vasculature. We evaluated the effect of hemopexin (HPX) therapy, mediated via an adeno-associated virus, to the progression of atherosclerosis in BT and a phenylhydrazine-induced model of intravascular hemolysis. In addition, we evaluated the effect of deferiprone (DFP)-mediated iron chelation in the progression of atherosclerosis in BT mice. Aortic en face and aortic root lesion area analysis revealed elevated plaque accumulation in both male and female BT mice compared with WT mice. Hemopexin therapy was able to decrease plaque accumulation in both BT mice and mice on our phenylhydrazine (PHZ)-induced model of hemolysis. DFP decreased atherosclerosis in BT mice but did not provide an additive benefit to HPX therapy. Our data demonstrate for the first time that the underlying pathophysiology of BT leads to accelerated atherosclerosis and shows that heme contributes to atherosclerotic plaque development in BT. NEW & NOTEWORTHY This work definitively shows for the first time that beta-thalassemia leads to accelerated atherosclerosis. We demonstrated that intravascular hemolysis is a prominent feature in beta-thalassemia and the resulting increases in free heme are mechanistically relevant. Adeno-associated virus (AAV)-hemopexin therapy led to decreased free heme and atherosclerotic plaque area in both beta-thalassemia and phenylhydrazine-treated mice. Deferiprone-mediated iron chelation led to deceased plaque accumulation in beta-thalassemia mice but provided no additive benefit to hemopexin therapy.

Stormwater infiltration basins have been used extensively around the world to restore urban hydrology towards more natural flow and water quality regimes. There is, however, significant uncertainty in the fate of infiltrated water and accompanying contaminants that depends on multiple factors including media characteristics, interactions with downslope vegetation, legacy contaminants, and presence of underground infrastructure. Understanding the influence of such factors is thus central to the design and siting of infiltration basins. An extensive field program was established to collect monthly data on ground water quality, including nutrients and major ion concentrations, in a bore network downstream of a stormwater infiltration basin in Victoria, Australia. The groundwater samples were analysed for temperature, pH, EC, turbidity, major ions (Na + , Ca 2+ , K + , Mg 2+ , Cl - , SO 4 2- , NO 3 - , CO 3 2- , HCO 3 - ), NOx and heavy metals. The collected data were used to understand the origin and fate of water and solutes in the subsurface and their interactions with the soil matrix. The results revealed that Ca-HCO 3 , Na-Cl water types predominate in the study area, grouped in 3 clusters; shallow fresh groundwater in the vicinity of the basin (near basin), deep saline groundwater further downstream of the basin (near-stream) and a mid-section where rock-water interaction (Na-HCO 3 water) through cation exchange control the chemistry of groundwater. The results also suggest that as the water moves downstream of the basin, it experiences significant evapotranspiration and concentration due to the presence of deep-rooted vegetation. The results suggest that while infiltration basins can remove infiltrated contaminants, the infiltrated stormwater can mobilise legacy contaminants such as nitrate. Overall, the efficacy of infiltration basins in urban regions depends substantially on the downstream vegetation, urban underground infrastructure and the presence of legacy contaminants in the soils. These all need to be considered in the design of stormwater infiltration basins., (© 2023. The Author(s).)

Introduction: The tumor microbiome (TM) has been linked to pancreatic cancer prognosis. Specific microbes can confer tumor resistance to therapies. Early knowledge of the TM at time of diagnosis would be clinically relevant for precision therapy based on microbial composition. However, it is difficult to define the TM prior to surgical resection., Methods: In this pilot feasibility study, patients underwent Endoscopic Ultrasound-Fine Needle Aspiration (EUS-FNA) biopsy of pancreatic adenocarcinoma. These samples were analyzed using 16S rRNA and internal transcribed spacer (ITS) sequencing for characterization of the tumor bacteria and fungi., Result: After in silico decontamination and comparison to non-matched tumor, we were able to characterize the TM in biopsies, which was comparable to the TM from surgical specimens., Discussion: EUS-FNA biopsy may represent a feasible modality to characterize the pancreatic TM prior to surgical resection with proper decontamination strategies and improvements in matched controls., Competing Interests: Author JW is founder and owner of Resphera Biosciences LLC. Author FM has a pending patent in microbiome profiling and is part of the SAB for Neologics Bio. The remaining 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 © 2023 Wright, Bartelli, Baydogan, White, Kim, Bhutani and McAllister.)

Background: Tenosynovial giant cell tumor (TGCT) is a benign proliferative disease affecting synovial membranes. There are 2 forms, localized (L-TGCT) and diffuse (D-TGCT), which although histologically similar behave differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess current practice, how the patients' presentation affected their outcome, as well as review the recurrence rates and complications., Methods: A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data were collected on age at presentation, radiologic pattern of disease, location of disease, treatment provided, and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years., Results: There were 61.7% female patients with a mean age of 39 (range, 11-76) years. L-TGCT accounted for 85 (69.1%) cases and D-TGCT for 38 (30.9%). The most prevalent preoperative symptoms were a palpable mass (78/123) and pain (65/123). Radiologically confirmed recurrence in the operative group was noted in 14.5% (16/110) cases. This comprised 4% (3/75) of operatively treated L-TGCT and 37% (13/35) of operatively treated D-TGCT. Patients with pain on presentation and those with erosive changes on presenting magnetic resonance imaging (MRI) were more likely to have persistent postoperative pain ( P  < .001 for both). Where patients had both preoperative pain and erosive changes, 57.1% had postoperative pain. Thirteen cases were managed nonoperatively where symptoms were minimal, with 1 case requiring surgery at a later date., Conclusion: Outcomes of TGCT management are dependent on the disease type, extent of preoperative erosive changes, and presence of preoperative pain. These data are useful for counseling patients regarding the outcomes of surgical intervention and help guide the timing of intervention., Level of Evidence: Level III, retrospective cohort study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online.

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13 C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on participants with Parkinson's disease and multiple system atrophy as well as age- and sex-matched healthy participants with typical development. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items (3.4 Finger tapping, 3.5 Hand movements, 3.6 Pronation-supination movements of hands, 3.7 Toe tapping, and 3.8 Leg agility) [1] underwent processing to fast Fourier [5] and amor and bump continuous wavelet transforms [6], [7], [8], [9], [10], [11], [12], [13]. Images of the signals and their transforms [4], [5], [6] of the five repetitive tasks of each participant were randomly expressed as panels on an electronic framework for rating by 35 trained examiners who did not know the source of the original output [14]. The team of international raters completed ratings of the signals and their transforms independently using criteria like the scoring systems for live assessments of movements in human participants [1,2]. The raters scored signals and transforms for deficits in the sustained performance of rhythmic movements (interruptions, slowing, and amplitude decrements) often observed in people with Parkinson's disease [15], [16], [17], [18], [19], [20]. Raters were first presented the images of the signals and transforms of a man with multiple system atrophy as a test and a retest in a different random order. After the raters completed the assessments of the man with multiple system atrophy, they were presented random test and retest panels of the images of signals and transforms of ten participants with Parkinson's disease who completed a single rating session. After the raters completed the assessments of the participants with Parkinson's disease who completed one set of ratings, they were presented random test and retest panels of the images of signals and transforms of (A) ten participants with Parkinson's disease and (B) eight age- and sex-match healthy participants with typical development who completed two rating session separated by a month or more [15], [16], [17], [18], [19], [20]. The data provide a framework for further analysis of the acquired information. Additionally, the data provide a template for the construction of electronic frameworks for the remote analysis by trained raters of signals and transforms of rhythmic processes to verify that the systems are operating smoothly without interruptions or changes in frequency and amplitude. Thus, the data provide the foundations to construct electronic frameworks for the virtual quality assurance of a vast spectrum of rhythmic processes. The dataset is a suitable template for solving unsupervised and supervised machine learning algorithms. Readers may utilize this procedure to assure the quality of rhythmic processes by confirming the absence of deviations in rate and rhythm. Thus, this procedure provides the means to confirm the quality of the vast spectrum of rhythmic processes., 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., (© 2023 The Author(s).)

To probe the causal importance of the human posteromedial cortex (PMC) in processing the sense of self, we studied a rare cohort of nine patients with electrodes implanted bilaterally in the precuneus, posterior cingulate, and retrosplenial regions with a combination of neuroimaging, intracranial recordings, and direct cortical stimulations. In all participants, the stimulation of specific sites within the anterior precuneus (aPCu) caused dissociative changes in physical and spatial domains. Using single-pulse electrical stimulations and neuroimaging, we present effective and resting-state connectivity of aPCu hot zone with the rest of the brain and show that they are located outside the boundaries of the default mode network (DMN) but connected reciprocally with it. We propose that the function of this subregion of the PMC is integral to a range of cognitive processes that require the self's physical point of reference, given its location within a spatial environment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Doping is a powerful strategy for enhancing the performance of ceria (CeO 2 ) nanomaterials in a range of catalytic, photocatalytic, biomedical, and energy applications. The present review summarizes recent developments in the doping of ceria nanomaterials with metal and non-metal dopants for selected applications. The most important metal dopants are grouped into s, p, d, and f block elements, and the relevant synthetic methods, novel properties, and key applications of metal doped ceria are collated and critically discussed. Non-metal dopants are similarly examined and compared with metal dopants using the same performance criteria. The review reveals that non-metal (N, S, P, F, and Cl) doped ceria has mainly been synthesized by calcination and hydrothermal methods, and it has found applications mostly in photocatalysis or as a cathode material for LiS batteries. In contrast, metal doped ceria nanomaterials have been prepared by a wider range of synthetic routes and evaluated for a larger number of applications, including as catalysts or photocatalysts, as antibacterial agents, and in devices such as fuel cells, gas sensors, and colorimetric detectors. Dual/co-doped ceria containing both metals and non-metals are also reviewed, and it is found that co-doping often leads to improved properties compared with single-element doping. The review concludes with a future outlook that identifies unaddressed issues in the synthesis and applications of doped ceria nanomaterials., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)