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Abstract Background The translational domain is a complex subfield of the biomedical life sciences focused on bridging the gap between scientific research and clinical application, with the ultimate goal of improving patient care through healthcare innovations. Professionals in this field, ranging from researchers to clinicians and industry experts, require specific core competencies. These include communication, collaboration, boundary crossing, innovation, and the ability to integrate diverse scientific domains. Methods We investigated the translational competencies acquired most by life science students who participated in a six-month challenge-based course at a Dutch graduate school. Seventeen students were part of the 2021 cohort, supervised by five biomedical experts serving as their clients. Quantitative and qualitative student survey data (n = 10), and semi-structured expert interview data (n = 4) were collected after completion of the course in 2021. Two existing translational competency frameworks were used to categorize and rank the acquired competencies, highlighting those most developed and relevant during the translational challenge-based course. Results Communication was the most listed competency category by both students and experts, and a new competency category was identified named Self-Development Tools, which included competencies related to decision-making, reflection, feedback, and creative thinking. Student data also showed that the course influenced their choice in pursuing a translational career path. Conclusions This study provides insight into key translational competencies acquired by students during a six-month challenge-based course and insight into competencies that may be part of their continued education after graduation from both student and expert perspectives. These findings are relevant for both educators and prospective employers in the translational domain as they apply a novel ranking to the existing literature on translational competencies and elaborate on how to prepare life sciences graduates towards a translational career.

Abstract Background Addiction medicine providers have a key role in HIV prevention amidst rising HIV incidence in persons who inject drugs (PWID). Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are vastly underutilized in this population. Inpatient hospitalization represents a potential touchpoint for initiation of HIV prophylaxis, though little research explores the role of addiction providers. Here we describe rates of PrEP/PEP delivery to hospitalized PWID seen by an Addiction Consult Service (ACS) at an urban, essential hospital. Methods We performed a cross-sectional study of hospitalized patients who were seen by the ACS from January 1, 2020 to December 31, 2022 and had plausible injection drug use. We calculated the proportion of patients who received a new prescription for PrEP/PEP at discharge. We used descriptive statistics to characterize demographics, substance use, reason for admission, and indications for PrEP/PEP. Secondarily, we calculated the monthly proportion of all patients discharged from the hospital with PrEP/PEP who were seen by the ACS compared to those not seen by the ACS. Results The average monthly proportion of ACS consults with plausible injection drug use who received PrEP/PEP was 6.4%. This increased from 4.2% in 2020 to 7.5% in 2022. Those seen by the ACS who received PrEP/PEP had high rates of opioid use disorder (97.5%), stimulant use disorder (77.8%), and homelessness (58.1%); over half were admitted for an injection-related infection. The indications for PrEP/PEP were injection drug use only (70.6%), followed by combined injection and sexual risk (20.2%); 71.9% of prescriptions were for PrEP and 28.1% for PEP. Overall, the ACS was involved in 83.9% of hospital-wide discharges with PrEP/PEP prescriptions (n = 242). Conclusions PWID who were seen by the ACS received PrEP/PEP prescriptions at rates exceeding national averages. The ACS was also involved with the care of the majority of admitted patients who received PrEP/PEP at discharge. While PrEP/PEP use for PWID remains low, the inpatient ACS represents a key resource to improve uptake by leveraging the reachable moment of an inpatient hospitalization.

Abstract Background Translational researchers (TRs) fulfill various roles across clinical, educational, and research domains with the ultimate goal of positively impacting patients. Mentorship has been recognized as an important means of career support for TRs, particularly when navigating the complex translational research pipeline and adapting to evolving roles. In response, the Erasmus + PATHWAY project developed and piloted an extra-curricular online preparatory course and mentorship program in 2019 and 2020 to help TRs build mentorship skills, develop their careers, and create online peer-to-peer learning opportunities. Methods To assess the pilot online mentorship program, a longitudinal exploratory mixed method study was conducted. Results Mentees and mentors from both years reported that they joined the program to learn mentorship skills, gain career support, and expand their (international) network. Analysis of evaluation forms indicated that the online preparatory course was evaluated largely positively, with participants suggesting improvements for future iterations. Results of a follow-up survey in 2022 revealed that mentorship was considered helpful in supporting TRs’ work in translational research, and an online mentorship program was useful, provided it included interactive online training, multiple mentee-mentor matching rounds, compatible time zones and professional experience for matched pairs, active program moderation with offline activities, and effective online tools. Conclusions This study revealed the mentorship needs of TRs and their recommendations for international online mentorship. The innovative PATHWAY program’s online format, mentee-driven matching, and preparatory training for both mentees and mentors contribute to the development of mentorship for the general translational community that could potentially have broader applications, especially in a post-COVID-19 environment.

Abstract Chronic wounds represent a significant global health concern, statistically impacting 1–2% of the population in developed countries throughout their lifetimes. These wounds cause considerable discomfort for patients and necessitate substantial expenditures of time and resources for treatment. Among the emerging therapeutic approaches, medicated dressings incorporating bioactive molecules, including natural compounds, are particularly promising. Hence, the objective of this study was to develop novel antimicrobial dressings for wound treatment. Specifically, polycaprolactone membranes were manufactured using the electrospinning technique and subsequently coated with natural polyelectrolytes (chitosan as a polycation and a mixture of manuka honey with essential oils nanoemulsions as a polyanion) employing the Layer-by-Layer assembly technique. Physico-chemical and morphological characterization was conducted through QCM-D, FTIR-ATR, XPS, and SEM analyses. The results from SEM and QCM-D demonstrated successful layer deposition and coating formation. Furthermore, FTIR-ATR and XPS analyses distinguished among different coating compositions. The coated membranes were tested in the presence of fibroblast cells, demonstrating biocompatibility and expression of genes coding for VEGF, COL1, and TGF-β1, which are associated with the healing process (assessed through RT-qPCR analysis). Finally, the membranes exhibited excellent antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, with higher bacterial strain inhibition observed when cinnamon essential oil nanoemulsion was incorporated. Taken together, these results demonstrate the potential application of nanocoated membranes for biomedical applications, such as wound healing.

The role of electrical stimulation in peripheral nerve regeneration is reviewed, including a brief background and proposed mechanism of action. Studies in animal as well as human models are reviewed. Current recommendations and future directions are addressed.

Category: Ankle; Ankle Arthritis Introduction/Purpose: Obesity is an ongoing public health epidemic with wide-ranging implications for orthopaedic surgery. Bariatric surgery has been shown to be an effective method for weight reduction. This retrospective cohort study aimed to compare rates of reoperation between patients who underwent primary ankle arthrodesis (AA) and those who underwent total ankle arthroplasty (TAA) after undergoing bariatric surgery. Methods: Utilizing data from PearlDiver, patients who received primary AA or TAA with prior history of bariatric surgery to a cohort without prior bariatric surgery were retrospectively analyzed for reoperations. Both cohorts were propensity-matched based on age, sex and Charlson Comorbidity Index in a 1:4 ratio. Indications for reoperation included revision, prosthetic joint infection (PJI), hardware removal, adjacent joint fusion, and local open reduction internal fixation (ORIF). Kaplan-Meier survival analysis and hazard ratios were calculated for five years after the procedure. Results: Of the 801 patients with prior history of bariatric surgery, 519 (65%) underwent AA, while 282 (35%) underwent TAA. At 5 years post-operatively, patients who had undergone AA showed a higher incidence of adjacent joint fusion if they had prior history of bariatric surgery (Hazard ratio: 1.79, 95% Confidence Interval: 1.23 - 2.61, P-value < 0.001). No differences in reoperation rates were observed for PJI, hardware removal and ORIF. At 5 years, patients who had undergone TAA with history of bariatric surgery showed no difference in the incidence of revision, PJI, hardware removal, ORIF and adjacent joint fusion as compared to patients who underwent TAA with no history of bariatric surgery. Conclusion: Our findings suggest that patients undergoing primary TAA displayed comparable reoperation rates regardless of prior bariatric surgery history over a five-year post-procedure period. In contrast, patients undergoing primary AA exhibited an increased risk of adjacent joint fusions if they had history of bariatric surgery, although the rates of reoperation due to PJI, ORIF, and hardware removal remained comparable. Notably, our results do not position a prior history of bariatric surgery as a significant determinant in reoperation rates. These insights offer valuable guidance for orthopedic surgeons navigating the complexities of surgical interventions in the context of bariatric surgery.

Abstract The McDonald Islands, together with Heard Island and the Kerguelen Archipelago, are volcanic islands on the mostly submerged Kerguelen Plateau, and the products of the long‐lived Kerguelen mantle plume (at least 130 Myr; Coffin et al., 2002, https://doi.org/10.25919/jw5f‐ad35). The first multibeam bathymetry data acquired around the Heard and McDonald islands reveal > 70 sea knolls surrounding the McDonald Islands and three sea knolls north of Heard Island. Rocks dredged from McDonald Islands sea knolls include fresh vesicular phonolitic lavas, phonolitic obsidian, phonolitic pillow fragments, and one basanite. These are the first phonolites sampled from the seafloor on the Kerguelen Plateau. Dredging of one sea knoll north of Heard Island recovered basaltic lavas. Lavas from the sea knolls are young, returning 40Ar/39Ar plateau ages of 73.7 ± 15.1 ka to 7.0 ± 2.7 ka for McDonald Islands sea knoll phonolites and 9.0 ± 1.3 ka for the Heard Island sea knoll. We define a new magma series, the McDonald Series, characterized by low εHf (−3.9 to −4.4) and lower Δ207Pb/204Pb (4.5–4.8) and Δ208Pb/204Pb (79–85) than all other lavas on the Kerguelen Plateau. This newly defined series is the product of a relatively young (Pleistocene‐Holocene) phase of volcanism produced by a distinct component of the Kerguelen mantle plume. We propose that McDonald Series phonolites together with 53.4 Ma lavas previously dredged from Ninetyeast Ridge provide evidence for zonation of the Kerguelen mantle plume.

Enterobacterales include foodborne pathogens of importance to public health and are often targeted in food surveillance programs as both safety and hygiene indicators. Furthermore, Enterobacterales are important in the context of antimicrobial resistance dissemination, also impacting infection treatment efficacy. In this study, the prevalence and characteristics of Enterobacterales in UK retail foods were examined. From 110 retail food samples, 253 Enterobacterales were recovered, with 16S rRNA sequencing revealing a diverse species community, including enteropathogens; the most common were Proteus mirabilis and Escherichia coli (18% each). Antimicrobial resistance was common, with 160/253 (63%) isolates being resistant to at least 1 antimicrobial. Resistance to all tested antimicrobials was observed. Thirteen percent of isolates were multidrug resistant, including 2 isolates each resistant to 8 or 9 of 9 antimicrobials tested. Klebsiella isolates possessed relatively higher levels of antimicrobial resistance to other species. Hafnia, Kluyvera, and Proteus isolates produced significantly higher biofilm biomass than Klebsiella (p = 0.038, 0.028, and 0.042, respectively) or Escherichia (p = 0.001, 0.008, and 0.001, respectively). Simultaneous curli fimbriae and cellulose production was noted in 7% of isolates at 37 °C, but not at 15 °C. This research demonstrates a high diversity of Enterobacterales within UK retail foods, alongside notable antimicrobial resistance phenotypes in enteropathogenic species, highlighting the need for effective surveillance and interventions.

Competing uses for nearshore coastal space, such as aquaculture, have complex environmental and ecological interactions with surrounding seagrass meadows. Oyster aquaculture is among the fastest-growing aquaculture segments in the United States, and it brings concerns such as increased sedimentation from farm maintenance operations and altered water quality through oyster filtration. Changes in seagrass coverage and growth are common indicators of ecological health used to determine anthropogenic impacts on nearshore environments. This study characterized the effects of a research-scale adjustable long-line oyster aquaculture system on the health of adjacent seagrass meadows in Copano Bay, TX. Four Halodule wrightii meadows were identified at various distances from the research site: 100 m upstream (upstream), directly adjacent (0 m), 30 m downstream (30 m), and 60 m downstream (60 m). Sites were monitored for 1) seagrass health, 2) water quality parameters, and 3) sediment deposition. Over the 18-week sampling period, no significant differences (p>0.05) were found for water quality variables or sediment grain-size analysis using a one-way ANOVA. A linear mixed-effects model was used for repeated measures of seagrass data, with no effect of the site found on mean seagrass length, coverage, or maximum length (p>0.05). These results suggest that seagrass health indicators were unaffected by proximity to the oyster system. It was concluded that an oyster research aquaculture system of the type and size at the project location had no major negative or positive impact on seagrass meadow health due to high background variability and the overall minor footprint of the oyster farm across a comparatively large spatial extent.

Abstract Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

Repurposing generic drugs as new treatments for life-threatening diseases such as cancer is an exciting yet largely overlooked opportunity due to a lack of market-driven incentives. Nonprofit organizations and other non-manufacturers have been ramping up efforts to repurpose widely available generic drugs and rapidly expand affordable treatment options for patients. However, these non-manufacturers find it difficult to obtain regulatory approval in the U.S. Without a straightforward path for approval and updating drug labeling, non-manufacturers have relied on off-label use of repurposed drugs. This limits the broad clinical adoption of these drugs and patient access. In this paper, we explore the regulatory landscape for repurposing of small molecule generic drugs within the U.S. We describe case studies of repurposed drugs that have been successfully incorporated into clinical treatment guidelines for cancer without regulatory approval. To encourage greater adoption of generic drugs in clinical practice–that is, to encourage the repurposing of these drugs–we examine existing Food and Drug Administration (FDA) pathways for approval of new uses or indications for generic drugs. We show how non-manufacturers, who are generally more active in generic drug repurposing than manufacturers, could utilize existing regulatory authorities and pathways, and we describe the challenges they face. We propose an extension of the existing 505(b)(2) new drug application (NDA) approval pathway, called a “labeling-only” 505(b)(2) NDA, that would enable non-manufacturers to seek approval of new indications for well-established small molecule drugs when multiple generic products are already available. It would not require new chemistry, manufacturing, and controls (CMC) data or introducing new drug products into the marketplace. This pathway would unlock innovation broadly and enable patients to benefit from the enormous potential of low-cost generic drugs.

Study region: South-east Mediterranean France Study focus: Urbanisation and climate change are producing unprecedented flood risks. Urbanisation increases storm peak discharge and flooded area. Building in the flood plain exposes more people and infrastructure to floods. This study examines the impact of urbanisation over 3 decades (1988/90–2020) on flood risk in SE France. Building footprint layers were used to quantify urban growth, and peak discharge and flooded area were modeled for 3 12-hr rainfall events: 80 mm, 140 mm, and 200 mm. Building growth ranged from 28 % to 65 %. Total imperviousness grew at a rate that was equal to or greater than built area. The relative increase in peak discharge was greatest for the 80-mm event (+12.2 %) and diminished to its lowest value for the 200-mm event (+2.4 %). New hydrological insights for the region: Flooded area increased proportionately to changes in peak discharge, but mean growth in flooded building footprint area was almost 43 times greater than growth in flooded area. New buildings within the flooded perimeter contributed more to flood risk than changes in peak discharge and flooded area. Planning legislation limited growth close to channels, but flood risk grew rapidly beyond in less restricted areas. Building footprint data provide an accurate approach to mapping changes in flood risk with urbanisation.

Abstract Introduction Atopic dermatitis is associated with intense itch, which has been shown to cause sleep disruption that significantly impacts the lives of patients with atopic dermatitis. Despite this, little is known about its burden to the healthcare system and society. This study aimed to quantify the economic burden of itch-related sleep loss in moderate-to-severe atopic dermatitis in the UK. Methods A literature-based decision-analytic model was developed from a healthcare payer and societal perspective. The model quantifies the economic burden by linking the severity of itch to the number of days of sleep disruption. The model captures the direct costs of healthcare resource utilization and treatment alongside the indirect costs of productivity loss from absenteeism and presenteeism at work over a 5-year time horizon. The patient population considered was patients aged ≥ 15 years with moderate-to-severe atopic dermatitis and itch-related sleep disruption. Results The model estimated that itch-related sleep disruption as a result of moderate-to-severe atopic dermatitis would affect an average of 821,142 people over the time horizon (2022 to 2026). This translates into an average net economic burden of £3.8 billion (£4687 per patient), with an average of 172 million days being affected by sleep disruption per year in the UK. The greatest contributor to the annual average net economic burden was productivity loss from absenteeism and presenteeism, each accounting for 34%. The direct costs (treatment costs and healthcare resource use) accounted for 32% of the net economic burden. The results showed a high and gradually increasing economic burden over the 5-year time horizon. Conclusions Sleep disruption has a high economic burden and reducing itch may provide substantial direct and indirect savings. Quantifying the economic burden of itch-related sleep loss may provide support for analyses to inform public health policies for treatment of atopic dermatitis, particularly within the moderate-to-severe level.

Abstract Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1–2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient’s wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient’s microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.

Background & Aims: Liver sinusoidal endothelial cells (LSECs) are important in liver development, regeneration, and pathophysiology, but the differentiation process underlying their tissue-specific phenotype is poorly understood and difficult to study because primary human cells are scarce. The aim of this study was to use human induced pluripotent stem cell (hiPSC)-derived LSEC-like cells to investigate the differentiation process of LSECs. Methods: hiPSC-derived endothelial cells (iECs) were transplanted into the livers of Fah−/−/Rag2−/−/Il2rg−/− mice and assessed over a 12-week period. Lineage tracing, immunofluorescence, flow cytometry, plasma human factor VIII measurement, and bulk and single cell transcriptomic analysis were used to assess the molecular and functional changes that occurred following transplantation. Results: Progressive and long-term repopulation of the liver vasculature occurred as iECs expanded along the sinusoids between hepatocytes and increasingly produced human factor VIII, indicating differentiation into LSEC-like cells. To chart the developmental profile associated with LSEC specification, the bulk transcriptomes of transplanted cells between 1 and 12 weeks after transplantation were compared against primary human adult LSECs. This demonstrated a chronological increase in LSEC markers, LSEC differentiation pathways, and zonation. Bulk transcriptome analysis suggested that the transcription factors NOTCH1, GATA4, and FOS have a central role in LSEC specification, interacting with a network of 27 transcription factors. Novel markers associated with this process included EMCN and CLEC14A. Additionally, single cell transcriptomic analysis demonstrated that transplanted iECs at 4 weeks contained zonal subpopulations with a region-specific phenotype. Conclusions: Collectively, this study confirms that hiPSCs can adopt LSEC-like features and provides insight into LSEC specification. This humanised xenograft system can be applied to further interrogate LSEC developmental biology and pathophysiology, bypassing current logistical obstacles associated with primary human LSECs. Impact and implications: Liver sinusoidal endothelial cells (LSECs) are important cells for liver biology, but better model systems are required to study them. We present a pluripotent stem cell xenografting model that produces human LSEC-like cells. A detailed and longitudinal transcriptomic analysis of the development of LSEC-like cells is included, which will guide future studies to interrogate LSEC biology and produce LSEC-like cells that could be used for regenerative medicine.

Communication is often impaired in individuals with Parkinson’s disease (PD), typically secondary to sensorimotor deficits impacting voice and speech. Language may also be diminished in PD, particularly for production and comprehension of verbs. Evidence exists that verb processing is influenced by motor system modulation suggesting that verb deficits in PD are underpinned by similarities in the neural representations of actions that span motor and semantic systems. Conversely, subtle differences in cognition in PD may explain difficulty in processing of complex syntactic forms, which increases cognitive demand and is linked to verb use. Here we investigated whether optimizing motor system support for vocal function (improving loudness) affects change in lexical semantic, syntactic, or informativeness aspects of spoken discourse. Picture description narratives were compared for 20 Control participants and 39 with PD, 19 of whom underwent Lee Silverman Voice Treatment (LSVT LOUD®). Treated PD narratives were also contrasted with those of untreated PD and Control participants at Baseline and after treatment. Controls differed significantly from the 39 PD participants for verbs per utterance, but this difference was largely driven by untreated PD participants who produced few utterances but with verbs, inflating their verbs per utterance. Given intervention, there was a significant increase in vocal loudness but no significant changes in language performance. These data do not support the hypothesis that targeting this speech motor system results in improved language production. Instead, the data provide evidence of considerable variability in measures of language production across groups, particularly in verbs per utterance.

Abstract Background Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling. Methods This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti. Results Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman’s rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09–0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35–0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47–0.49). Conclusions In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area.

At its core, political economy analysis involves examination of the relationship between the state and the market. A number of country case studies have emerged in recent years that aim to identify political economy factors facilitating or impeding health sector reforms towards universal coverage. In this commentary, we expand Nannini and colleagues’ analysis to elaborate on how political economy analyses can better inform policy design towards more successful reforms in low- and middle-income countries (LMICs) by drawing more heavily on improved research design and theory. We suggest three ways that political economy studies could make deeper claims by historicizing analyses, going comparative and/or by grounding findings more deeply in theory.

Abstract Background An inclusive academic environment is pivotal to ensure student well-being and a strong sense of belonging and authenticity. Specific attention for an inclusive learning environment is particularly important during a student’s transition to higher education. At Utrecht University’s Medical School, explorative interviews with students from minority groups indicated they did not always feel included during the orientation programme of their academic education. We, therefore, developed a bias awareness training with theoretical and practical components on diversity and inclusion for peer-mentors who are assigned to each first-year student at the start of university. Methods At the end of the orientation programme, we investigated the effectiveness of the training for two consecutive years using two measurements. Firstly, we investigated the behavioural changes in the peer-mentors through a (self-reporting) questionnaire. Additionally, we measured the perceived inclusion of the first-year students, divided into belonging and authenticity, using a validated questionnaire. Results Our results show that peer-mentors found the training useful and indicated it enabled them to create an inclusive atmosphere. Overall, students experienced a high level of inclusion during the orientation programme. After the first year, the bias training was adjusted based on the evaluations. This had a positive effect, as mentors felt they were significantly more able to provide an inclusive orientation in the second year of this study. In line with this, students experienced an increased level of authenticity specifically due to the peer-mentor in the second year as compared to the first. Conclusions We conclude that training peer-mentors is an effective way to increase awareness and to ensure an inclusive atmosphere during the start of higher education.

Abstract The reactive transport code CrunchClay was used to derive effective diffusion coefficients (D e ), clay porosities (ε), and adsorption distribution coefficients (K D ) from through-diffusion data while considering accurately the influence of unavoidable experimental biases on the estimation of these diffusion parameters. These effects include the presence of filters holding the solid sample in place, the variations in concentration gradients across the diffusion cell due to sampling events, the impact of tubing/dead volumes on the estimation of diffusive fluxes and sample porosity, and the effects of O-ring-filter setups on the delivery of solutions to the clay packing. Doing so, the direct modeling of the measurements of (radio)tracer concentrations in reservoirs is more accurate than that of data converted directly into diffusive fluxes. While the above-mentioned effects have already been described individually in the literature, a consistent modeling approach addressing all these issues at the same time has never been described nor made easily available to the community. A graphical user interface, CrunchEase, was created, which supports the user by automating the creation of input files, the running of simulations, and the extraction and comparison of data and simulation results. While a classical model considering an effective diffusion coefficient, a porosity and a solid/solution distribution coefficient (D e –ε–K D ) may be implemented in any reactive transport code, the development of CrunchEase makes it easy to apply by experimentalists without a background in reactive transport modeling. CrunchEase makes it also possible to transition more easily from a D e –ε–K D modeling approach to a state-of-the-art process-based understanding modeling approach using the full capabilities of CrunchClay, which include surface complexation modeling and a multi-porosity description of the clay packing with charged diffuse layers.

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010–31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.

Ethnic discrimination during pregnancy is linked to maternal psychological distress, adverse birth outcomes and increased offspring morbidity and mortality. An evolutionary perspective reframes offspring health issues as a risk to maternal fitness. We argue that kin may be evolutionarily motivated to buffer psychosocial stressors for the mother during pregnancy. Previously, we found that the relationship of a pregnant woman with her own mother (fetus’ maternal grandmother) had a positive association on maternal prenatal psychology, above and beyond her relationship with her fetus’ father. Here, we ask if grandmothers buffer mothers’ prenatal psychological distress from ethnic discrimination. Using self-report data collected from 216 pregnant Latina women living in Southern California, we found discrimination to be significantly, positively associated with depression, anxiety, and stress in linear regression models. Maternal grandmother communication attenuated the association of discrimination and all three psychological distress measures, adjusting for the mother's relationship with the father. Maternal grandmother emotional support similarly significantly moderated the relationship of discrimination with depression and anxiety. We did not observe any significant interactions for paternal grandmother relationships. Geographic proximity was not a significant stress buffer. Results suggest the important role maternal grandmothers play in perinatal mental health, and that these benefits exist uncoupled from geographic proximity.

Background: Dual-mobility (DM) total hip arthroplasty (THA) combines the stabilization advantage provided by large head articulation with the low friction advantage provided by small head articulation. There is momentum for DM to be used in a wider selection of patients, with some advocating for DM to be the routine primary total hip construct. Further investigation is needed to determine whether the use of DM in younger adults is validated by aggregate data. Our objective was to review the literature for the clinical performance of DM THA in patients aged 55 years and younger. Methods: A systematic review of the literature was performed according to the guidelines of Preferred Reporting in Systematic Reviews and Meta-Analyses. Inclusion in the review required clinical outcome reporting for DM primary THA in ambulatory patients aged 55 years or younger. The risk of bias was appraised using the Cochrane risk of bias in nonrandomized studies of interventions and the quality of the evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework. Results: Across a sample of 1048 cases, the frequency weighted term of follow-up was 87.7 months. The pooled rate of revision was 9.5%. The Harris Hip Score significantly improved from 49.1 preoperatively to 93 postoperatively. The Postel-Merle d'Aubigné score significantly improved from 10.5 preoperatively to 17.1 postoperatively. Conclusions: The literature demonstrates satisfactory short-term outcomes with a mitigated risk of dislocation for DM used as primary THA in patients aged 55 years and younger. The current findings suggest that third-generation designs provide reduced rates of intraprosthetic dislocation and improved survivorship.

Introduction: Contrast-enhanced ultrasound (CEUS) is a modality of growing interest because of its improved detection rates when evaluating lesions and better success rates when administering interventions, compared to standard ultrasound. Along with its diagnostic value, the possibilities for therapeutic innovation with CEUS are immense. While there is much discussion of CEUS and its potential applications, there is a scarcity of studies characterizing the current state of CEUS research. Bibliometric analysis, a method of gaining an overview of a body of literature, quantitatively analyzes large amounts of information within publications to reveal trends. This study used bibliometric analysis to characterize the state and nature of the 100 most-cited publications on CEUS. Methods: We identified the 100 most-cited publications on contrast-enhanced ultrasound using the Scopus database. We recorded various bibliometric data points from these publications, with additional data collected for the 25 most-cited publications. Data were analyzed via R, R studio, and VOSviewer. Results: Our analysis of the top 100 publications revealed that 38 of the listed first authors were from the United States. Eleven articles were in Radiology, six were in Ultraschall in der Medizin, and six were in Ultrasound in Medicine and Biology, with mean citation counts of 269.2, 433.3, and 291.7 per publication, respectively. The University of Virginia Health System produced the most publications in the top 100. Seventeen of the top 25 most-cited articles were clinical practice guidelines. Four of the top five papers were clinical practice guidelines pertaining to hepatocellular carcinoma. Conclusion: In conclusion, several interesting trends were demonstrated in our bibliometric analysis. The most heavily cited articles from the top 100 were published between 2010 and 2019, which is in contrast to the finding that the previous decade contained more articles published in the top 100. This trend indicates a significant scientific impact from those articles published from 2010 to 2019. The substantial number of articles addressing applications of CEUS in diagnosing and treating liver diseases correlates closely with their global disease burden; therefore, this finding potentially explains the rise in impactful research production within the field. This study is the first to characterize the landscape of CEUS research, and future studies should further this work as the field continues to develop. Thus, our analysis reveals many important findings in the current state of CEUS research and its impact on medical imaging.

Trade law and competition law have grown up in their separate silos. This means that restraints by the states and restraints by private parties are treated in separate boxes, and with few exceptions, they have been treated so through the years. Yet, some of the worst restraints that do some of the greatest damage are best characterized by the synergy between the two. These trade-and-competition, or hybrid public/private, restraints fall under the radar screen, and defendants in litigation play one set of laws off against the other, hiding behind limits and immunities. This is the Blind Spot of the Article’s title – the space between the silos. This Article unearths the Blind Spot, gives examples of what we know and what we need to know, and proposes a methodology to illuminate and eliminate the Blind Spot.

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction, however, the molecular pathways resulting in endothelial barrier dysfunction and vascular leakage are only sparsely understood. Here, Biering et al. show that SARS-CoV-2 spike protein is sufficient to induce barrier dysfunction and vascular leak. They show a role for integrins, TGF-beta, ECM remodeling enzymes, and glycosaminoglycans in this S-mediated barrier dysfunction.

Beaver dams increase water flow gradients and nitrate removal far more than seasonal climate extremes. An expanding beaver range is an ecosystem feedback to climate change which could improve water quality.

Abstract Copper isotope analysis has emerged as a promising tool for understanding genetic processes in Cu ore deposits. However, applications of this analytical technique to Archean Cu deposits have been extremely limited, even though Archean terranes are among the most economically endowed on Earth. As such, this study presents the first Cu isotope analysis of an Archean Cu deposit, the Mesoarchean Carlow Castle hydrothermal Cu‐Co‐Au deposit. Archean primary Cu sulfide ore samples and Cenozoic supergene Cu ore samples were analyzed. Primary ore samples are isotopically light, with δ65Cu values ranging between −0.80 ± 0.02‰ and 0.00 ± 0.007‰, whilst supergene samples are isotopically heavier and range between −0.50 ± 0.01‰ and 0.62 ± 0.005‰. In primary ore samples, a relationship is observed between the Cu isotope signature, ore grade, and alteration assemblage that records the isotopic and physicochemical evolution of the Carlow Castle deposit's hydrothermal ore‐forming system. A mafic igneous source is suggested as a metal source in the Carlow Castle Cu‐Co‐Au deposit. The limited heavy isotopic fractionation of supergene Cu ore samples in this study is interpreted to reflect limited redox cycling of Cu due to in situ oxidative weathering of vein‐hosted Cu sulfides in the overlying Cenozoic supergene system. This differs from previously studied deposits where significant Cu transport and multiple stages of isotopic enrichment are often evident in supergene Cu enrichment layers. The results of this study suggest that Cu isotope analysis could be valuable in understanding genetic processes in hydrothermal Cu deposits, including Archean ore deposits and terranes.

Case: An 81 year old male with four failed aspirations presented with recurrent knee swelling following irrigation and debridement, which suggested the presence of a Morel-Lavallée lesion (MLL). This diagnosis was intraoperatively confirmed by separation of the tissue layers forming a space with accumulated fluid. Treatment consisted of doxycycline sclerodesis and tight closure of the tissue layers. The patient had a satisfactory outcome at 4 months. Conclusion: Resolution of Morel-Lavallée lesions requires prompt recognition and appropriate treatment. In the presence of a different diagnosis, recurrence of symptoms following treatment may indicate an MLL. Surgical treatment with doxycycline sclerodesis resulted in resolution of symptoms.

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon–bone interface healing by combining PRP with stem cell–seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells–seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

ABSTRACT Clostridium perfringens is a bacterial species of importance to both public and animal health. The gene optrA is the first gene that confers resistance to the tedizolid, a last-resort antimicrobial agent in human medicine. Herein, we whole-genome sequenced and analyzed one optrA-positive C. perfringens strain QHY-2 from Tibetan sheep in Qinghai province and identified one optrA plasmid pQHY-2. The plasmid shared similar structure with the optrA-positive plasmids p2C45 and p21-D-5b previously identified in C. perfringens, demonstrating the potential horizontal transmission of the optrA plasmids among C. perfringens strains. Annotation of the optrA-positive plasmids showed optrA and erm(A) located on a segment flanked by IS element IS1216E, and fexA, optrA, and erm(A) located on a segment flanked by IS element ISVlu1, which revealed the possible dissemination mechanism. Additionally, a Tn6218-like transposon carrying aac(6′)-aph(2″) and erm(B) was also detected on pQHY-2, demonstrating the transposition of Tn6218 and spread of antibiotic resistance among Clostridium bacteria. Molecular analysis indicated the optrA-positive plasmids belonged to a plasmid type distinct from the pCW3-like plasmids, pCP13-like plasmids, or pIP404-like plasmids. Further structure analysis showed they might be formed by inserting segments into plasmid pCPCPI53k-r1_1, which coexist with two pCW3-like plasmids and one pCP13-like plasmid in C. perfringens strain CPI 53k-r1 isolated from a healthy human in Finland. IMPORTANCE Antimicrobial resistance is now a global concern posing threats to food safety and public health. The pCW3-like plasmids can encode several main toxin genes and three antibiotic resistance genes (ARGs), including tetA(P), tetB(P), and erm(B), which used to be considered as the main carrier of ARGs in Clostridium perfringens. In this study, we found the optrA plasmids, which belonged to a novel plasmid type, could also harbor many other ARGs, indicating this type of plasmid might be the potential repository of ARGs in C. perfringens. Additionally, this type of plasmid could coexist with the pCW3-like plasmids and pCP13-like plasmids that encoded toxin genes associated with gastrointestinal diseases, which showed the potential threat to public health.

Abstract RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to protect against cell death in a range of preclinical cellular and animal models of diseases. SAR443060 (previously DNL747) is a selective, orally bioavailable, central nervous system (CNS)–penetrant, small‐molecule, reversible inhibitor of RIPK1. In three early‐stage clinical trials in healthy subjects and patients with AD or ALS (NCT03757325 and NCT03757351), SAR443060 distributed into the cerebrospinal fluid (CSF) after oral administration and demonstrated robust peripheral target engagement as measured by a reduction in phosphorylation of RIPK1 at serine 166 (pRIPK1) in human peripheral blood mononuclear cells compared to baseline. RIPK1 inhibition was generally safe and well‐tolerated in healthy volunteers and patients with AD or ALS. Taken together, the distribution into the CSF after oral administration, the peripheral proof‐of‐mechanism, and the safety profile of RIPK1 inhibition to date, suggest that therapeutic modulation of RIPK1 in the CNS is possible, conferring potential therapeutic promise for AD and ALS, as well as other neurodegenerative conditions. However, SAR443060 development was discontinued due to long‐term nonclinical toxicology findings, although these nonclinical toxicology signals were not observed in the short duration dosing in any of the three early‐stage clinical trials. The dose‐limiting toxicities observed for SAR443060 preclinically have not been reported for other RIPK1‐inhibitors, suggesting that these toxicities are compound‐specific (related to SAR443060) rather than RIPK1 pathway‐specific.

Abstract BackgroundBard is a conversational generative artificial intelligence (AI) platform released by Google (Mountain View, CA) to the public in May 2023. ObjectivesThis study investigates the performance of Bard on the American Society of Plastic Surgeons (ASPS) In-Service Examination to compare it to residents' performance nationally. We hypothesized that Bard would perform best on the comprehensive and core surgical principles portions of the examination. MethodsGoogle's 2023 Bard was used to answer questions from the 2022 ASPS In-Service Examination. Each question was asked as written with the stem and multiple-choice options. The 2022 ASPS Norm Table was utilized to compare Bard's performance to that of subgroups of plastic surgery residents. ResultsA total of 231 questions were included. Bard answered 143 questions correctly corresponding to an accuracy of 62%. The highest-performing section was the comprehensive portion (73%). When compared with integrated residents nationally, Bard scored in the 74th percentile for post-graduate year (PGY)-1, 34th percentile for PGY-2, 20th percentile for PGY-3, 8th percentile for PGY-4, 1st percentile for PGY-5, and 2nd percentile for PGY-6. ConclusionsBard outperformed more than half of the first-year integrated residents (74th percentile). Its best sections were the comprehensive and core surgical principle portions of the examination. Further analysis of the chatbot's incorrect questions might help improve the overall quality of the examination's questions.

IntroductionTranslational research is a subfield of the biomedical life sciences that focuses on clinically driven healthcare innovations. The workforce of this subfield, i.e., translational researchers, are diversely specialized and collaborate with a multitude of stakeholders from diverse disciplines in and outside academia in order to navigate the complex path of translating unmet clinical needs into research questions and ultimately into advancements for patient care. Translational researchers have varying responsibilities in the clinical, educational, and research domains requiring them to split their time two- or three-ways. Working between these domains and alongside peers who do not split their time as such, raises questions about the academic reward system used to recognize their performance, which mainly focuses on publication metrics within the research domain. What is unclear is how combining research tasks with tasks in the clinical and/or educational domains effects translational researchers and how they navigate the academic reward system.MethodsIn this exploratory interview study, semi-structured interviews were conducted to gain a deeper understanding of the current academic reward system for translational researchers. Stratified purposeful sampling was used to recruit 14 translational researchers from varying countries, subspecialties, and career stages. The interviews were coded after data collection was complete and arranged into three overarching result categories: intrinsic motivation, extrinsic factors, and ideal academic reward system and advice.ResultsWe found that these 14 translational researchers were intrinsically motivated to achieve their translational goals while working in settings where clinical work was reported to take priority over teaching which in turn took priority over time for research. However, it is the latter that was explained to be essential in the academic reward system which currently measures scientific impact largely based on publications metrics.ConclusionIn this study, translational researchers were asked about their thoughts regarding the current academic reward system. Participants shared possible structural improvements and ideas for specialized support on an individual, institutional, and also international level. Their recommendations focused on acknowledging all aspects of their work and led to the conclusion that traditional quantitative academic reward metrics do not fully align with their translational goals.

IntroductionChikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown. Here, we evaluated the protective efficacy of CHIKV-immune IgG enriched for binding to Fc-gamma receptor IIIa (FcγRIIIa) to select for IgG with enhanced Fc effector functions.MethodsTotal IgG was isolated from CHIKV-immune convalescent donors with and without additional purification by FcγRIIIa affinity chromatography. The enriched IgG was characterized in biophysical and biological assays and assessed for therapeutic efficacy during CHIKV infection in mice.ResultsFcγRIIIa-column purification enriched for afucosylated IgG glycoforms. In vitro characterization showed the enriched CHIKV-immune IgG had enhanced human FcγRIIIa and mouse FcγRIV affinity and FcγR-mediated effector function without reducing virus neutralization in cellular assays. When administered as post-exposure therapy in mice, CHIKV-immune IgG enriched in afucosylated glycoforms promoted reduction in viral load.DiscussionOur study provides evidence that, in mice, increasing Fc engagement of FcγRs on effector cells, by leveraging FcγRIIIa-affinity chromatography, enhanced the antiviral activity of CHIKV-immune IgG and reveals a path to produce more effective therapeutics against these and potentially other emerging viruses.

Background:. Chronic diabetic wounds are a significant issue that can be treated with topical hydrogel therapies. The aim of this study was to review the different compositions of hydrogel that have been developed and analyze their clinical relevance in the treatment of chronic diabetic wounds. Methods:. We conducted a scoping review in which twelve articles were selected for review after applying relevant inclusion and exclusion criteria using a two-reviewer strategy. Data extracted from these studies was used to answer the following research question: What is the composition of hydrogels used to treat chronic diabetic wounds and how effective are they? Results:. We analyzed five randomized controlled trials, two retrospective studies, three reviews, and two case reports. Hydrogel compositions discussed included mesenchymal stem cell sheets, carbomer, collagen, and alginate hydrogels, as well as hydrogels embedded with platelet-derived growth factor. Synthetic hydrogels, largely composed of carbomers, were found to have high levels of evidence supporting their wound healing properties, though few articles described their routine use in a clinical setting. Collagen hydrogels dominate the present-day hydrogel market in the clinical treatment of chronic diabetic wounds. The augmentation of hydrogels with therapeutic biomaterials is a new field of hydrogel research, with studies demonstrating promising early in vitro and in vivo animal studies demonstrating promising early results for in vitro and in vivo animal investigations. Conclusions:. Current research supports hydrogels as a promising topical therapy in the treatment of chronic diabetic wounds. Augmenting Food & Drug Administration-approved hydrogels with therapeutic substances remains an interesting early area of investigation.

Abstract Background In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. Methods This was a retrospective observational cohort study using US Renal Data System data for 2015–2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. Results The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). Conclusions Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

While visual literacy has been identified as a foundational skill in life science education, there are many challenges in teaching and assessing biomolecular visualization skills. Among these are the lack of consensus about what constitutes competence and limited understanding of student and instructor perceptions of visual literacy tasks. In this study, we administered a set of biomolecular visualization assessments, developed as part of the BioMolViz project, to both students and instructors at multiple institutions and compared their perceptions of task difficulty. We then analyzed our findings using a mixed-methods approach. Quantitative analysis was used to answer the following research questions: (1) Which assessment items exhibit statistically significant disparities or agreements in perceptions of difficulty between instructors and students? (2) Do these perceptions persist when controlling for race/ethnicity and gender? and (3) How does student perception of difficulty relate to performance? Qualitative analysis of open-ended comments was used to identify predominant themes related to visual problem solving. The results show that perceptions of difficulty significantly differ between students and instructors and that students’ performance is a significant predictor of their perception of difficulty. Overall, this study underscores the need to incorporate deliberate instruction in visualization into undergraduate life science curricula to improve student ability in this area. Accordingly, we offer recommendations to promote visual literacy skills in the classroom.

Forest fires burn an average of about 440 000 ha each year in southern Europe. These fires cause numerous casualties and deaths and destroy houses and other infrastructure. In order to elaborate on suitable firefighting strategies, complex interactions between human and environmental factors must be taken into account. In this study, we investigated the spatiotemporal evolution in the burned area over a 50-year period (1970–2019) and its interactions with topography (slope aspect and inclination) and vegetation type in southeastern France by exploiting the geographic information system (GIS) databases. Data were analyzed for two 25-year periods (1970–1994 and 1995–2019), since a new fire suppression policy was put into place after 1994, which focused on rapid extinction of fires in their early phase. In the last 25 years, the burned area decreased sharply, and the geographic distribution of fires also changed, especially in regions where large fires occur (Var administrative division). Elsewhere, even though forest fires remain frequent, the total extent of the burned area decreased substantially. Fire hotspots appear closer to built-up areas in the west, are randomly distributed in the east, and they almost completely disappear in the central region of the study area where there is a history of large fires. Slope orientation presents an increasingly important role in the second period; south-facing slopes are preferred the most by fire, and north-facing slopes are preferentially avoided. Even though the slope inclination is less affected by the new firefighting strategy, low slope inclinations are even more avoided after 1994. The greatest proportion of the burned area is strongly associated with the location of sclerophyllous vegetation clusters which exhibit highly fire prone and expand in area over time. Natural grasslands are also preferred by fire, while broadleaved, coniferous, and mixed forest are increasingly avoided by fire.

Abstract Early detection of diseases such as COVID-19 could be a critical tool in reducing disease transmission by helping individuals recognize when they should self-isolate, seek testing, and obtain early medical intervention. Consumer wearable devices that continuously measure physiological metrics hold promise as tools for early illness detection. We gathered daily questionnaire data and physiological data using a consumer wearable (Oura Ring) from 63,153 participants, of whom 704 self-reported possible COVID-19 disease. We selected 73 of these 704 participants with reliable confirmation of COVID-19 by PCR testing and high-quality physiological data for algorithm training to identify onset of COVID-19 using machine learning classification. The algorithm identified COVID-19 an average of 2.75 days before participants sought diagnostic testing with a sensitivity of 82% and specificity of 63%. The receiving operating characteristic (ROC) area under the curve (AUC) was 0.819 (95% CI [0.809, 0.830]). Including continuous temperature yielded an AUC 4.9% higher than without this feature. For further validation, we obtained SARS CoV-2 antibody in a subset of participants and identified 10 additional participants who self-reported COVID-19 disease with antibody confirmation. The algorithm had an overall ROC AUC of 0.819 (95% CI [0.809, 0.830]), with a sensitivity of 90% and specificity of 80% in these additional participants. Finally, we observed substantial variation in accuracy based on age and biological sex. Findings highlight the importance of including temperature assessment, using continuous physiological features for alignment, and including diverse populations in algorithm development to optimize accuracy in COVID-19 detection from wearables.

BackgroundApproximately 3.2%–6% of the general population harbor an unruptured intracranial aneurysm (UIA). Ruptured aneurysms represent a significant healthcare burden, and preventing rupture relies on early detection and treatment. Most patients with UIAs are asymptomatic, and many of the symptoms associated with UIAs are nonspecific, which makes diagnosis challenging. This study explored symptoms associated with UIAs, the rate of resolution of such symptoms after microsurgical treatment, and the likely pathophysiology.MethodsA retrospective review of patients with UIAs who underwent microsurgical treatment from January 1, 2014, to December 31, 2020, at a single quaternary center were identified. Analyses included the prevalence of nonspecific symptoms upon clinical presentation and postoperative follow-up; comparisons of symptomatology by aneurysmal location; and comparisons of patient demographics, aneurysmal characteristics, and poor neurologic outcome at postoperative follow-up stratified by symptomatic versus asymptomatic presentation.ResultsThe analysis included 454 patients; 350 (77%) were symptomatic. The most common presenting symptom among all 454 patients was headache (n = 211 [46%]), followed by vertigo (n = 94 [21%]), cognitive disturbance (n = 68[15%]), and visual disturbance (n = 64 [14%]). Among 328 patients assessed for postoperative symptoms, 258 (79%) experienced symptom resolution or improvement.ConclusionThis cohort demonstrates that the clinical presentation of patients with UIAs can be associated with vague and nonspecific symptoms. Early detection is crucial to prevent aneurysmal subarachnoid hemorrhage. It is imperative that physicians not rule out aneurysms in the setting of nonspecific neurologic symptoms.

Abstract Low‐relief, high‐elevation surfaces in mountain belts highlight the dynamic nature of landscapes and have provided evidence for changes in tectonics and/or climate. Yet quantifying when changes occurred from topographic data is challenging and relationships between erosion rate, lithology and precipitation are complex. In the Pyrenees, low‐relief, high elevation surfaces are found across both plutonic massifs and the surrounding softer rocks and channel steepness values are relatively uniform between these lithologies. This suggests a weak relationship between erosion rate and lithology despite a clear relationship between the drainage network configuration and the location of the plutonic rocks. We explore this conflicting evidence for strength of the relationship between lithology and erosion rate using a landscape evolution model which accounts for the contrast between bedrock and bedload erodibility. This contrast produces dispersed channel steepness values and predicts the in situ development of low‐relief surfaces, under steady forcing conditions.

Rural populations are more vulnerable to the impacts of COVID-19 compared to their urban counterparts as they are more likely to be older, uninsured, to have more underlying medical conditions, and live further from medical care facilities. We engaged the Southeastern MN (SEMN) community (N = 7,781, 51% rural) to conduct a survey of motivators and barriers to masking to prevent COVID-19. We also assessed preferences for types of and modalities to receive education/intervention, exploring both individual and environmental factors primarily consistent with Social Cognitive Theory. Our results indicated rural compared to urban residents performed fewer COVID-19 prevention behaviors (e.g. 62% rural vs. 77% urban residents reported wearing a mask all of the time in public, p

Summary: NanoDam is a technique for genome-wide profiling of the binding targets of any endogenously tagged chromatin-binding protein in vivo, without the need for antibodies, crosslinking, or immunoprecipitation. Here, we explain the procedure for NanoDam experiments in Drosophila, starting from a genetic cross, to the generation of sequencing libraries and, finally, bioinformatic analysis. This protocol can be readily adapted for use in other model systems after simple modifications.For complete details on the use and execution of this protocol, please refer to Tang et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure.

Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.