Female genital schistosomiasis (FGS) is a chronic disease manifestation of the waterborne parasitic infection Schistosoma haematobium that affects up to 56 million women and girls, predominantly in sub-Saharan Africa. Starting from early childhood, this stigmatizing gynaecological condition is caused by the presence of Schistosoma eggs and associated toxins within the genital tract. Schistosoma haematobium typically causes debilitating urogenital symptoms, mostly as a consequence of inflammation, which includes bleeding, discharge and lower abdominal pelvic pain. Chronic complications of FGS include adverse sexual and reproductive health and rights outcomes such as infertility, ectopic pregnancy and miscarriage. FGS is associated with prevalent human immunodeficiency virus and may increase the susceptibility of women to high-risk human papillomavirus infection. Across SSA, and even in clinics outside endemic areas, the lack of awareness and available resources among both healthcare professionals and the public means FGS is underreported, misdiagnosed and inadequately treated. Several studies have highlighted research needs and priorities in FGS, including better training, accessible and accurate diagnostic tools, and treatment guidelines. On 6 September, 2024, LifeArc, the Global Schistosomiasis Alliance and partners from the BILGENSA Research Network (Genital Bilharzia in Southern Africa) convened a consultative, collaborative and translational workshop: ‘Female Genital Schistosomiasis: Translational Challenges and Opportunities’. Its ambition was to identify practical solutions that could address these research needs and drive appropriate actions towards progress in tackling FGS. Here, we present the outcomes of that workshop – a series of discrete translational actions to better galvanize the community and research funders.

Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

The Centers for Disease Control and Prevention define 6 intervals of a pandemic: (1) investigation of cases, (2) recognition of the increased potential for ongoing transmission, (3) initiation of a pandemic wave, (4) acceleration of a pandemic wave, (5) deceleration of a pandemic wave, and (6) preparation for future pandemic waves. Each of these stages has 8 domains. Following China’s coronavirus disease 2019 (COVID-19) outbreak announcement, Israel’s National Emergency Medical Services (EMS) Organization immediately began working in conjunction with the Ministry of Health (MOH) to address the threat of the COVID-19 outbreak. This article will describe how a national EMS organization acted according to these pandemic intervals and domains. In the initial stages, EMS managed a checkpoint in the international airport voluntarily testing people for febrile symptoms. Calls to the dispatch centers that aroused the suspicion of COVID-19 resulted in EMS transport to the hospital with protective gear. During the period of first exposure, the scope of the medical emergency number was increased to include questions concerning coronavirus, telemedicine, and home sampling by protected EMS workers. In the contagion stages, epidemiological tests were conducted by the MOH, and EMS began operating dedicated telephone triage, mass drive-through sampling, and finally, administration of vaccinations.

The end-Cretaceous (K/Pg) mass extinction event is the most recent and well-understood of the “big five” and triggered establishment of modern terrestrial ecosystem structure. Despite the depth of research into this event, our knowledge of upper Maastrichtian terrestrial deposits globally relies primarily on assemblage-level data limited to a few well-sampled formations in North America, the Hell Creek and Lance Formations. These assemblages disproportionally affect our interpretations of this important interval. Multiple investigations have quantified diversity patterns within these assemblages, but the potential effect of formation-level size-dependent taphonomic biases and their implications on extinction dynamics remains unexplored. Here, the relationship between taphonomy and body size of the Hell Creek Formation and Lance Formation dinosaurs and mammals are quantitatively analyzed. Small-bodied dinosaur taxa (<70 kg) are consistently less complete, unlikely to be articulated, and delayed in their description relative to their large-bodied counterparts. Family-level abundance (particularly skeletons) is strongly tied to body mass, and the relative abundance of juveniles of large-bodied taxa similarly is underrepresented. Mammals show similar but nonsignificant trends. The results are remarkably similar to those from the Campanian-aged Dinosaur Park Formation, suggesting a widespread strong taphonomic bias against the preservation of small taxa, which will result in their seemingly depauperate diversity within the assemblage. This taphonomically skewed view of diversity and abundance of small-bodied taxa amid our best late Maastrichtian samples has significant implications for understanding speciation and extinction dynamics (e.g., size-dependent extinction selectivity) across the K/Pg boundary.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers’ levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I2 statistic. Results: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. Conclusions: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.

We conducted a series of field experiments to determine the role of several factors that might contribute to the inconsistent control of common lambsquarters with glyphosate. Experiments in 2006 and 2007 determined common lambsquarters response to glyphosate under a wide range of measured environmental conditions. Glyphosate was applied at 0.84 kg ae ha−1 plus 3.8 kg ha−1 ammonium sulfate (AMS) to 10-cm-tall plants on 18 dates in each year and to 20-cm-tall plants on 18 dates in 2007. Control was less for six application dates relative to control for 48 other dates. Poor control was attributed to rainfall on one of these six dates, but for the other five dates, regression analysis did not identify any significant relationships between environmental conditions (relative humidity, temperature at time of treatment, or minimum and maximum temperature pre- and posttreatment) and control, even though a wide range of conditions occurred. To determine the effects of plant growth stage on control, glyphosate was applied at 0.1 to 3.2 kg ha−1 plus 3.8 kg ha−1 AMS to 10- and 20-cm-tall plants at four sites. The glyphosate ED50 value (the effective dose that reduced shoot mass by 50% relative to nontreated plants) was 1.9 to 3.0 times greater for 20- than 10-cm-tall plants in three site-years, but was not affected by plant height in one site-year. We also conducted experiments to determine the effect of rainfall on glyphosate efficacy. Across years, common lambsquarters control increased from 44 to 75% as the interval between glyphosate application (0.84 kg ha−1 + 3.8 kg ha−1 AMS) and simulated rainfall increased from 0.5 to 4.0 h, respectively. Our results did not identify environmental conditions that explained reduced glyphosate efficacy in all cases, but they suggest that rainfall after application and plant height can be important factors contributing to the inconsistent control of common lambsquarters.