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Abstract Transportation insecurity has profound impacts on the health and wellbeing of teenage parents and their children, who are at particularly high risk for missed clinic visits. In other settings, clinic-offered rideshare interventions have reduced the rates of missed visits. We conducted a one-arm pre-post time series analysis of missed visits before and after a pilot study rideshare intervention within a clinic specializing in the care of teenage parents and their children. We compared the number of missed visits during the study with the number during the preceding year (July 2019–March 2020), as well as the cost difference of missed visits, adjusting for inflation and clinic census. Of 153 rides scheduled, 106 (69.3%) were completed. Twenty-nine (29.9%) of 97 clinic visits were missed during the study period, compared to 145 (32.7%) of 443 comparison period visits (p-value = 0.59). The estimated cost difference of missed visits including intervention costs was a net savings of $90,830.32. However, the standardized cost difference was a net excess of $6.90 per clinic visit. We found no difference in rates of missed visits or costs, though likely impacted by the low census during the SARS-CoV-2 pandemic. Given the potential to improve health disparities exacerbated by the pandemic, further research is warranted into the impact and utility of clinic-offered rideshare interventions.

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) and financial hardship are associated with increased likelihood of heavier alcohol use and health challenges in adulthood among persons living with HIV (PWH). We examined whether retrospectively captured lifetime drinking trajectories are a pathway through which childhood hardships affect current health in a sample of 365 adult PWH. Childhood economic hardship and ACEs were used as main predictors. Measures of alcohol use included age at first drink and lifetime drinking trajectories. Health indicators included health-related quality of life, frailty, number of comorbidities, and symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD). Structural equation modeling (SEM) was applied to estimate both direct and indirect pathways between childhood hardship and physical and mental health. Participants were mostly male; Black (84%); and averaged 48 years of age. SEM results supported both direct and indirect pathways between childhood experiences and adult health. ACEs were connected to physical health directly and mental health both directly and indirectly through age at first drink and drinking heaviness during ages 10–20. Childhood economic hardship related to mental health indirectly through higher drinking levels during ages 10–20. Childhood adverse experiences, economic hardship, and early drinking patterns appear to accumulate, resulting in later life physical and mental health concerns for PWH. Findings support taking a life course approach to health. This includes considering individual trauma histories in HIV care engagement and taking preventative approaches which support the economic and social well-being of vulnerable children to improve health in subsequent decades. [ABSTRACT FROM AUTHOR]

Since 1971, the decennial censuses of England and Wales have underpinned the construction of various local level deprivation measures. Many policy-related and academic studies have used deprivation scores calculated cross-sectionally to identify geographical areas in need of regeneration and to explain spatial variations in health outcomes. However, such an approach masks the sometimes very distinct challenges faced in areas with different deprivation histories. There is, therefore, a need to consider the deprivation trajectories of areas over a long time run. This can then enable, for example: monitoring the effects of industry closure; assessing the impacts of area-based planning initiatives; and determining whether a change in the level of deprivation leads to changes in health outcomes. It can also be used to consider what interventions may be linked with positive changes and which could then possibly be implemented elsewhere. Here we extend previous work to cover a 50-year period using input variables relating to employment, housing, and car accessibility, from the six censuses from 1971 to 2021. We identify areas of persistent (dis-)advantage, those areas which have improved their deprivation situation, and those places where the situation has worsened. We cross-classify the changing deprivation measurements with the Office for National Statistics (ONS) Supergroups area classification to thereby determine how different types of area are faring. On average, areas are less deprived in 2021 than in 1971. However, the trajectories of the input variables and of overall deprivation are not linear. The earlier decades are distinctive in rapid falls in non-home ownership and lack of car access but rises and falls in unemployment. The more recent decades have seen rises in non-home ownership and household overcrowding. Geographically, there has been a shift from a widespread level of deprivation, including in more rural areas in 1971, to being more concentrated in urban areas in the 21st Century. [ABSTRACT FROM AUTHOR]

At the start of the Zika virus (ZIKV) epidemic in 2015, ZIKV spread across South and Central America, and reached parts of the southern United States placing pregnant women at risk for fetal microcephaly, fetal loss, and other adverse pregnancy outcomes associated with congenital ZIKA syndrome (CZS). For this reason, testing of a safe and efficacious ZIKV vaccine remains a global health priority. Here we report that a single immunization with Ad26.M.Env ZIKV vaccine, when administered prior to conception, fully protects pregnant rhesus macaques from ZIKV viral RNA in blood and tissues with no adverse effects in dams and fetuses. Furthermore, vaccination prevents ZIKV distribution to fetal tissues including the brain. ZIKV associated neuropathology was absent in offspring of Ad26.M.Env vaccinated dams, although pathology was limited in fetuses from non-immunized, challenged dams. Vaccine efficacy is associated with induction of ZIKV neutralizing antibodies in pregnant rhesus macaques. These data suggest the feasibility of vaccine prevention of CZS in humans. [ABSTRACT FROM AUTHOR]

The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development. Fetal brain development is dependent on the maternal supply of long chain polyunsaturated fatty acids (LC-PUFAs). Here, the authors show that pregnancy-induced liver-X-receptor (LXR) signaling in the maternal liver promotes the synthesis of LC-PUFA-containing phospholipids for export to the fetus. [ABSTRACT FROM AUTHOR]

Saturn's mid-sized icy moons have complex relationships with Saturn's interior, the rings, and with each other, which can be expressed in their shapes, interiors, and geology. Observations of their physical states can, thus, provide important constraints on the ages and formation mechanism(s) of the moons, which in turn informs our understanding of the formation and evolution of Saturn and its rings. Here, we describe the cratering records of the mid-sized moons and the value and limitations of their use for constraining the histories of the moons. We also discuss observational constraints on the interior structures of the moons and geologically-derived inferences on their thermal budgets through time. Overall, the geologic records of the moons (with the exception of Mimas) include evidence of epochs of high heat flows, short- and long-lived subsurface oceans, extensional tectonics, and considerable cratering. Curiously, Mimas presents no clear evidence of an ocean within its surface geology, but its rotation and orbit indicate a present-day ocean. While the moons need not be primordial to produce the observed levels of interior evolution and geologic activity, there is likely a minimum age associated with their development that has yet to be determined. Uncertainties in the populations impacting the moons makes it challenging to further constrain their formation timeframes using craters, whereas the characteristics of their cores and other geologic inferences of their thermal evolutions may help narrow down their potential histories. Disruptive collisions may have also played an important role in the formation and evolution of Saturn's mid-sized moons, and even the rings of Saturn, although more sophisticated modeling is needed to determine the collision conditions that produce rings and moons that fit the observational constraints. Overall, the existence and physical characteristics of Saturn's mid-sized moons provide critical benchmarks for the development of formation theories. [ABSTRACT FROM AUTHOR]

Three manufacturers sell artificial pancreas systems in the United States for management of Type 1 Diabetes. Given the life-saving task required of an artificial pancreas there needs to be a high level of trust and safety in the devices. This evaluation sought to find the adjusted safety event reporting rate and themes along with device-associated risk in events reported utilizing the MAUDE database. We searched device names in the MAUDE database over the period from 2016 until August 2023 (the date of retrieval). Thematic analysis was performed using dual-reviewer examination with a 96% concurrence. Relative risk (RR) was calculated for injury, malfunction, and overall, for each manufacturer, as well as adjusted event rate per manufacturer. Most events reported related to defects in the manufacturing of the casing materials which resulted in non-delivery of therapy. Tandem Diabetes Care, Inc. had an adjusted event rate of 50 per 100,000 units and RR of 0.0225. Insulet had an adjusted event rate of 300 per 100,000 units and RR of 0.1684. Medtronic has an adjusted event rate of 2771.43 per 100,000 units and RR of 20.7857. The newer Medtronic devices show improvements in likely event rate. While the artificial pancreas is still in its infancy, these event rates are not at an acceptable level for a device which can precipitate death from malfunctions. Further exploration into safety events and much more research and development is needed for devices to reduce the event rates. Improved manufacturing practices, especially the casing materials, are highly recommended. The artificial pancreas holds promise for millions but must be improved before it becomes a true life-saving device that it has the potential to become. [ABSTRACT FROM AUTHOR]

Tissue engineered scaffolds are needed to support physiological loads and emulate the micrometer-scale strain gradients within tissues that guide cell mechanobiological responses. We designed and fabricated micro-truss structures to possess spatially varying geometry and controlled stiffness gradients. Using a custom projection microstereolithography (μSLA) system, using digital light projection (DLP), and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel monomers, three designs with feature sizes < 200 μm were formed: (1) uniform structure with 1 MPa structural modulus (E ) designed to match equilibrium modulus of healthy articular cartilage, (2) E = 1 MPa gradient structure designed to vary strain with depth, and (3) osteochondral bilayer with distinct cartilage (E = 1 MPa) and bone (E = 7 MPa) layers. Finite element models (FEM) guided design and predicted the local mechanical environment. Empty trusses and poly(ethylene glycol) norbornene hydrogel-infilled composite trusses were compressed during X-ray microscopy (XRM) imaging to evaluate regional stiffnesses. Our designs achieved target moduli for cartilage and bone while maintaining 68–81% porosity. Combined XRM imaging and compression of empty and hydrogel-infilled micro-truss structures revealed regional stiffnesses that were accurately predicted by FEM. In the infilling hydrogel, FEM demonstrated the stress-shielding effect of reinforcing structures while predicting strain distributions. Composite scaffolds made from stiff μSLA-printed polymers support physiological load levels and enable controlled mechanical property gradients which may improve in vivo outcomes for osteochondral defect tissue regeneration. Advanced 3D imaging and FE analysis provide insights into the local mechanical environment surrounding cells in composite scaffolds. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes. Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database. Results: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of postoperative complications did not differ between the NAST- and upfront surgery-treated patients (55% vs. 51%; p = 0.643), and steroid treatment for drug toxicity did not influence the complication rate (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.4–3; p = 0.826). No significant differences in postoperative morbidity were observed in terms of seroma (23% vs. 11%; p = 0.570) or lymphedema (36% vs. 51%; p = 0.550). The rate of achieving a textbook outcome was comparable for the two groups (61% vs. 57%; p = 0.641). Conclusions: The surgical outcomes after lymph node dissections were comparable between the patients who received NAST and those who had upfront surgery, indicating that surgery can be safely performed after NAST with TT or ICI for stage III melanoma. [ABSTRACT FROM AUTHOR]

Cassava is a crucial food crop in the western region of Kenya, producing 60% of the country's production. It is mainly grown by small-scale farmers for subsistence use, with any surplus being sold. Many cassava landraces from the western region have been seriously affected by two viral diseases, cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) but have not been conserved, together with associated farmer knowledge, in national or international germplasm repositories. This study aimed at collecting landraces and associated farmers' knowledge, identifying collected cultivars and determining their genetic diversity. In addition, the incidence and distribution of CMD and CBSD was determined. A collection mission was undertaken covering five counties of western Kenya; Kakamega, Bungoma, Busia, Migori and Homabay. A total of 256 cassava samples were collected from 203 households. In addition, leaf samples were taken from 210 perceived improved varieties and genotyped with the landraces using DArTSeq to confirm whether any of the landraces were infact improved varieties. Stakes from the collected landraces were established in the glasshouse for sprouting and subsequent virus indexing. Molecular diagnostics revealed that 60.5% of collected samples were CMD positive with 33.2% of these being East African Cassava Mosaic Virus and 27.3% being African Cassava Mosaic Virus, and 22.7% were CBSD positive with 12.1% being Cassava Brown Streak Virus and 10.6% being Ugandan Cassava Brown Streak Virus. Interestingly CMD causing viruses were found in all the counties but CBSD-associated viruses were not detected in Kakamega or Bungoma counties. Dual infection of the CMD and CBSD-causing viruses were also found on collected cassava landraces from Busia, Homabay and Migori. These results confirm the urgent need for deployment of varieties with dual resistance to CMD and CBSD. Key informant interviews highlight the importance of cooking as well as eating properties of cassava and yield and time to maturity amongst other characteristics. A total of 57 unique genotypes (39 landraces and 18 improved varieties) were identified. Cassava germplasm from western Kenya was found to have low genetic variability, and this, coupled with the incidences of CMD and CBSD emphasizes the urgent development and deployment of varieties with dual virus resistance. Farmer and consumer preferences should be used to inform priority traits in cassava breeding programmes for the region. [ABSTRACT FROM AUTHOR]

Introduction: Multiparametric MRI (mpMRI) parameters of pT3a prostate cancer have not been examined in large cohort studies. Therefore, we aimed to identify factors associated with up-staging of mpMRI cT3a in post-operative histopathological confirmation. Methods: Retrospective analysis of a prospectively maintained database of a single UK cancer centre. Only cT3a cases who underwent robotic-assisted radical prostatectomy (RARP) were included (N = 383). MRI and specimen histopathology was reviewed independently by expert uro-radiologists and uro-histopathologists, respectively. Factors included age, BMI, prostate-specific antigen (PSA) level, biopsy international society of urological pathology (ISUP) grade, Prostate Imaging Reporting & Data System (PI-RADS®) score, tumour size, tumour coverage of gland (%), gland weight and surgical margins were analysed as predictors of pT3a prostate cancer. Results: N = 383. Mean age 66 years (58–71), mean BMI 27.1 kg/m2 (25.0–30.0). 314 (82.0%) cases down- unchanged or down-staged, and 69 (18.0%) cases upstaged. PSA level (P = 0.002), PI-RADS score (P < 0.001) and ISUP grade (P < 0.001) are positively associated with upstage categories. ISUP grade ≥3 (OR 5.45, CI 1.88, 9.29, P < 0.002), PI-RADS score ≥4 (OR 3.92, CI 1.88–9.29, P < 0.001) and tumour coverage (OR 1.06, CI 1.05–1.08, P < 0.001) significantly positively associated with upstaging disease, with concurrent decreased probability of downstaging (OR 0.55, 0.14, 0.44, respectively, P < 0.05). Tumour coverage was positively correlated with increasing positive surgical margins (P < 0.05). Capsular contact > 15 mm was very unlikely to be upstaged (OR 0.36, CI 0.21–0.62, P < 0.001), aligning with published results past the widely accepted significant level for extracapsular disease on MRI. Conclusion: The study has identified PSA level, ISUP, PI-RADS score, tumour volume and percentage coverage are key predictive factors in cT3a upstaging. This study uniquely shows tumour coverage percentage as a predictor of cT3a upstaging on mpMRI. ISUP is the strongest predictor, followed by PI-RADS score and tumour coverage of gland. Multi-institutional studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Low skeletal muscle index/density (SMI/SMD) is prevalent in cancer, adversely prognostic and associated with tumour stage and the systemic inflammatory response (SIR). Age and SMI/SMD has not been widely studied. The present study analyses the association between age and SMI/SMD after adjustment for other clinicopathological factors. Patients undergoing resectional surgery for TNM Stage I-III disease within the West of Scotland between 2011 and 2014 were identified. A single CT slice was obtained from each patients staging CT scan. SMI and SMD were stratified normal/abnormal. The SIR was stratified using Systemic Inflammatory Grade (SIG). When stratified by age (< 50/50s/60s/70s/80+), 39%/38%/48%/62%/74% and 27%/48%/64%/82%/92% of patients had a low SMI and SMD respectively (both p < 0.001). Older age (OR 1.47, p < 0.001), female sex (OR 1.32, p = 0.032), lower socioeconomic deprivation (OR 1.15, p = 0.004), higher ASA (OR 1.30, p = 0.019), emergency presentation (OR 1.82, p = 0.003), lower BMI (OR 0.67, p < 0.002) and higher SIG (OR 1.23, p < 0.001) were independently associated with low SMI. Older age (OR 2.28, p < 0.001), female sex (OR 1.38, p = 0.038), higher ASA (OR 1.92, p < 0.001), emergency presentation (OR 1.71, p = 0.023), and higher SIG (OR 1.37, p < 0.001) were independently associated with lower SMD. Tumour factors were not independently associated with either SMI/SMD. Age was a major factor associated with low SMI/SMD in patients with colon cancer. Therefore, in these patients it is likely that this represents largely constitutional body composition as opposed to being a disease mediated effect. Adjustment for age is required when considering the cancer mediated effect on SMI/SMD in patients with colon cancer. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries (LiBs) are used globally as a key component of clean and sustainable energy infrastructure, and emerging LiB technologies have incorporated a class of per- and polyfluoroalkyl substances (PFAS) known as bis-perfluoroalkyl sulfonimides (bis-FASIs). PFAS are recognized internationally as recalcitrant contaminants, a subset of which are known to be mobile and toxic, but little is known about environmental impacts of bis-FASIs released during LiB manufacture, use, and disposal. Here we demonstrate that environmental concentrations proximal to manufacturers, ecotoxicity, and treatability of bis-FASIs are comparable to PFAS such as perfluorooctanoic acid that are now prohibited and highly regulated worldwide, and we confirm the clean energy sector as an unrecognized and potentially growing source of international PFAS release. Results underscore that environmental impacts of clean energy infrastructure merit scrutiny to ensure that reduced CO2 emissions are not achieved at the expense of increasing global releases of persistent organic pollutants. A new class of PFAS (bis-perfluoroalkyl sulfonamides) used in lithium-ion batteries have been released to the environment internationally. This places lithium-ion batteries at the nexus of CO2 reduction and release of recalcitrant aquatic contaminants. [ABSTRACT FROM AUTHOR]

Paracetamol is one of the most commonly used over-the-counter medications. Experimental studies suggest a possible stress-suppressing effect of paracetamol in humans facing experimental stress-inducing paradigms. However, no study has investigated whether paracetamol and steroid hormones covary over longer time frames and under real-life conditions. This study addresses this gap by investigating associations between steroid hormones (cortisol, cortisone, and testosterone) and paracetamol concentrations measured in human hair, indexing a timeframe of approximately three months. The data came from a large community sample of young adults (N = 1002). Hair data were assayed using liquid chromatography–tandem mass spectrometry. Multiple regression models tested associations between paracetamol and steroid hormones, while adjusting for a wide range of potential confounders, such as sex, stressful live events, psychoactive substance use, hair colour, and body mass index. Almost one in four young adults from the community had detectable paracetamol in their hair (23%). Higher paracetamol hair concentrations were robustly associated with more cortisol (β = 0.13, ηp = 0.016, p < 0.001) and cortisone (β = 0.16, ηp = 0.025, p < 0.001) in hair. Paracetamol and testosterone hair concentrations were not associated. Paracetamol use intensity positively correlated with corticosteroid functioning across several months. However, a potential corticosteroid-inducing effect of chronic paracetamol use has yet to be tested in future experimental designs. [ABSTRACT FROM AUTHOR]

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59–0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57–0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66–0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63–1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72–1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain. [ABSTRACT FROM AUTHOR]

The webinar series and workshop titled "Trust Your Gut: Establishing Confidence in Gastrointestinal Models - An Overview of the State of the Science and Contexts of Use" was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting. [ABSTRACT FROM AUTHOR]

Summary: There is imminent refracture risk in elderly individuals for up to six years, with a decline thereafter except in women below 75 who face a constant elevated risk. Elderly men with fractures face the highest mortality risk, particularly those with hip and vertebral fractures. Targeted monitoring and treatment strategies are recommended. Purpose: Current management and interventions for osteoporotic fractures typically focus on bone mineral density loss, resulting in suboptimal evaluation of fracture risk. The aim of the study is to understand the progression of fractures to refractures and mortality in the elderly using multi-state models to better target those at risk. Methods: This prospective, observational study analysed data from the AGES-Reykjavik cohort of Icelandic elderly, using multi-state models to analyse the evolution of fractures into refractures and mortality, and to estimate the probability of future events in subjects based on prognostic factors. Results: At baseline, 4778 older individuals aged 65 years and older were included. Elderly men, and elderly women above 80 years of age, had a distinct imminent refracture risk that lasted between 2–6 years, followed by a sharp decline. However, elderly women below 75 continued to maintain a nearly constant refracture risk profile for ten years. Hip (30–63%) and vertebral (24–55%) fractures carried the highest 5-year mortality burden for elderly men and women, regardless of age, and for elderly men over 80, lower leg fractures also posed a significant mortality risk. Conclusion: The risk of refracture significantly increases in the first six years following the initial fracture. Elderly women, who experience fractures at a younger age, should be closely monitored to address their long-term elevated refracture risk. Elderly men, especially those with hip and vertebral fractures, face substantial mortality risk and require prioritized monitoring and treatment. [ABSTRACT FROM AUTHOR]

Here we introduce graphPAF, a comprehensive R package designed for estimation, inference and display of population attributable fractions (PAF) and impact fractions. In addition to allowing inference for standard population attributable fractions and impact fractions, graphPAF facilitates display of attributable fractions over multiple risk factors using fan-plots and nomograms, calculations of attributable fractions for continuous exposures, inference for attributable fractions appropriate for specific risk factor → mediator → outcome pathways (pathway-specific attributable fractions) and Bayesian network-based calculations and inference for joint, sequential and average population attributable fractions in multi-risk factor scenarios. This article can be used as both a guide to the theory of attributable fraction estimation and a tutorial regarding how to use graphPAF in practical examples. [ABSTRACT FROM AUTHOR]

Purpose: Intimate partner violence (IPV) interventions for young people involved with the child welfare and legal systems are critical. However, researchers have yet to systematically assess this knowledge area. Methods: We conducted a systematic review to identify IPV interventions targeting young people involved with the legal and/or child welfare system. Six electronic databases were searched for quantitative and qualitative peer-reviewed articles that focused on IPV victimization and/or perpetration; included child welfare and/or legal system-involved young people aged 10 to 24 years; delivered an intervention; and reported outcome(s). Three researchers independently screened captured article abstracts; two researchers conducted full-text eligibility assessments. Data were extracted and findings were narratively summarized and compared. Results: We identified seven eligible studies: two child welfare and five legal system studies. Three studies focused on IPV perpetration only; two on IPV victimization and perpetration; two on IPV victimization only. Only two studies mentioned IPV types. One intervention was culturally-tailored. Two studies assessed IPV as an outcome, with the one focused on educating about power dynamics in romantic relationships and improving communication skill deficits reporting significant IPV reductions. Other improved outcomes were present across studies (e.g., IPV knowledge, trauma symptoms, condom use). Conclusion: Few IPV interventions focus on young people involved with the child welfare and/or legal system. We call for more research on this topic that is trauma-informed, culturally relevant, and includes all genders. It should also include components related to gender and power and healthy communication and target multiple types of IPV victimization and perpetration. [ABSTRACT FROM AUTHOR]

Introduction: Patients with proctocolectomy and ileal pouch-anal anastomosis (PC-IPAA) face unique challenges in managing prostate cancer due to their hostile abdomens and heightened small bowel mucosa radiosensitivity. In such cases, external beam radiation therapy (EBRT) is contraindicated, and while brachytherapy provides a safer option, its oncologic effectiveness is limited. The Single-Port Transvesical Robot-Assisted Radical Prostatectomy (SP TV-RARP) offers promise by avoiding the peritoneal cavity. Our study aims to evaluate its feasibility and outcomes in patients with PC-IPAA. Methods: A retrospective evaluation was done on patients with PC-IPAA who had undergone SP TV-RARP from June 2020 to June 2023 at a high-volume center. Outcomes and clinicopathologic variables were analyzed. Results: Eighteen patients underwent SP TV-RARP without experiencing any complications. The median hospital stay was 5.7 h, with 89% of cases discharged without opioids. Foley catheters were removed in an average of 5.5 days. Immediate urinary continence was seen in 39% of the patients, rising to 76 and 86% at 6- and 12-month follow-ups. Half of the cohort had non-organ confined disease on final pathology. Two patients with ISUP GG3 and GG4 exhibited detectable PSA post-surgery and required systemic therapy; both had SVI, multifocal ECE, and large cribriform pattern. Positive surgical margins were found in 44% of cases, mostly Gleason pattern 3, unifocal, and limited. After 11.1 months of follow-up, no pouch failure or additional BCR cases were found. Conclusion: Patients with PC-IPAA often exhibit aggressive prostate cancer features and may derive the greatest benefit from surgical interventions, particularly given that radiation therapy is contraindicated. SP TV-RARP is a safe option for this group, reducing the risk of bowel complications and promoting faster recovery. [ABSTRACT FROM AUTHOR]

This study compared the use of delivering a single instruction (e.g., Who is it?) versus varied instructions (e.g., What's their name? Who is this? What about this one?) when teaching three children diagnosed with autism spectrum disorder (ASD) novel expressive label targets via direct telehealth. The present investigation utilized an adapted alternating treatments design nested into a multiple probe design, to teach participants to expressively label pictures of cartoon characters using either a single instruction or varied instructions. The goal of this study was to evaluate the acquisition, effectiveness, and efficiency of the two different procedures for each participant. The results demonstrated that while students learned all targets in both conditions, skill acquisition rates were slightly higher for the majority of participants using varied instructions via telehealth. [ABSTRACT FROM AUTHOR]

In this study, we took a close look at the Ocean Networks Canada's earthquake early warning system in southwestern British Columbia through analysis of the magnitude estimates by this system and characterization of site conditions for both onshore and offshore stations. Using magnitude values estimated at each station, over hundreds of notifications, we provided station terms to correct the magnitudes for stations that systematically generate high or low magnitude values. Moreover, by compiling a rich ground motion amplitude dataset and applying the horizontal-to-vertical spectral ratio method from Fourier amplitude of acceleration and response spectral acceleration, we investigated site characterization through evaluation of non-linear site response behavior and estimation of the site dominant frequency (fpeak) and its peak amplitude (Apeak) for each station. In general, no strong evidence of non-linearity is observed at any stations considering the magnitude-distance distribution of ground motions in this study. Offshore sites show fpeak and Apeak in the range of approximately 1.7–6 Hz and 0.4–1.2 (in base-10 log unit), respectively, whereas onshore sites show approximately 1–6 Hz for fpeak and 0.3–0.7 (in base-10 log unit) for Apeak. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK). Methods: Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28 days prior to surgery with continued treatment for 84 days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3 months) and 168 (6 months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3 months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS). Results: Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3 months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures. Conclusion: VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial. Plain Language Summary: Laser in situ keratomileusis (LASIK) is a very successful refractive surgery option for patients hoping to reduce or eliminate their need for spectacles. Signs and symptoms of dry eye disease are very common after LASIK owing to the transection of corneal nerves that occurs during the procedure, and many patients are advised to manage it with frequent instillation of artificial tears. This study evaluated the use of a varenicline solution nasal spray, a recently introduced pharmacologic option that stimulates natural tear production through activation of the trigeminal nerve pathway. This is the first study to evaluate the use of the varenicline solution nasal spray in patients after refractive surgery and demonstrates that it could represent a favorable, ocular surface-sparing option for patients to minimize the signs and symptoms of dry eye following LASIK, a procedure known to trigger symptoms of dry eye disease. [ABSTRACT FROM AUTHOR]

To develop a strategy for improvement of cassava (Manihot esculenta Crantz) productivity for climate change preparedness in Lamu County, Kenya, it was important to understand which cultivars farmers are growing. Landraces should be collected and conserved prior to replacement by improved cultivars to avoid erosion of genetic resources and associated farmer knowledge. In this study, 58 samples of landraces were collected from five administrative wards in Lamu County. These were SNP genotyped using low-density Diversity Array Technologies (DArT) DaRTSeq™ together with a reference set of 48 breeding lines, eight coastal and 45 inland landraces to aid identification of the collected samples. Genotyping results defined nine clades of duplicates and six unique clones. The most representative clone was selected from each clade of duplicates and combined with the unique clones giving a set of 15 different genotypes. None of the landraces or improved cultivars used in the reference panel were found in the genotyped collection. Discriminant Analysis of Principal Components revealed four clusters; Lamu germplasm, breeding lines, inland landraces and coastal landraces with low levels of differentiation between them. According to Wrights' F Statistics landraces from Lamu were most closely related to other coastal landraces (Fst = 0.0300), with greater differentiation from breeding lines (Fst = 0.0578) and inland landraces (Fst = 0.0632). Expected heterozygosity was highest for the breeding lines (0.275) and lowest for Lamu landraces (0.240), indicating a narrow genetic base. The results provide valuable information on genetic diversity and identify germplasm for conservation and future use. [ABSTRACT FROM AUTHOR]

Purpose: Describe spirituality’s role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors. Methods: This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants’ lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2–5 years ago were virtually recruited for participation. Participants completed virtual semi-structured interviews about their experiences with hope during cancer treatments and cancer survivorship and prepared narratives about their experiences. Thematic analyses were iteratively performed across the data set to identify final themes. Results: Ten Hispanic AYA cancer survivors (mean age 30.2, SD = 4.5) years participated in this pilot study. Seven participants (70%) were female, and three participants (30%) were male. Six participants (60%) experienced non-hematologic malignancies, and four participants (40%) experienced hematologic malignancies. Eight (80%) participants’ language preference was Spanish, while two (20%) participants’ language preference was English. The theme spirituality and subthemes living by faith, god as a resource, and spiritual gratitude were identified as concepts participants linked to their conceptualization of hope during cancer treatment and survivorship. Conclusions: Hope and spirituality may be conceptually linked to coping behaviors among Hispanic AYA cancer survivors. Hope through faith may be a learned spiritual value in Hispanic AYAs and might play a role in their spiritual and cognitive development. Further research is needed to explore the potentially protective value of hope and spirituality for the Hispanic AYA population. [ABSTRACT FROM AUTHOR]

The use of opportunistic computed tomography (CT) image-based biomarkers may be a low-cost strategy for screening older individuals at high risk for osteoporotic fractures and populations that are not sufficiently targeted. This review aimed to assess the discriminative ability of image-based biomarkers derived from existing clinical routine CT scans for hip, vertebral, and major osteoporotic fracture prediction. A systematic search in PubMed MEDLINE, Embase, Cochrane, and Web of Science was conducted from the earliest indexing date until July 2023. The evaluation of study quality was carried out using a modified Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. The primary outcome of interest was the area under the curve (AUC) and its corresponding 95% confidence intervals (CIs) obtained for four main categories of biomarkers: areal bone mineral density (BMD), image attenuation, volumetric BMD, and finite element (FE)-derived biomarkers. The meta-analyses were performed using random effects models. Sixty-one studies were included in this review, among which 35 were synthesized in a meta-analysis and the remaining articles were qualitatively synthesized. In comparison to the pooled AUC of areal BMD (0.73 [95% CI 0.71–0.75]), the pooled AUC values for predicting osteoporotic fractures for FE-derived parameters (0.77 [95% CI 0.72–0.81]; p < 0.01) and volumetric BMD (0.76 [95% CI 0.71–0.81]; p < 0.01) were significantly higher, but there was no significant difference with the pooled AUC for image attenuation (0.73 [95% CI 0.66–0.79]; p = 0.93). Compared to areal BMD, volumetric BMD and FE-derived parameters may provide a significant improvement in the discrimination of osteoporotic fractures using opportunistic CT assessments. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to 231,841 deaths and 940,243 hospitalisations in England, by the end of March 2023. This paper calculates the real-time infection hospitalisation risk (IHR) and infection fatality risk (IFR) using the Office for National Statistics Coronavirus Infection Survey (ONS CIS) and the Real-time Assessment of Community Transmission Survey between November 2020 to March 2023. The IHR and the IFR in England peaked in January 2021 at 3.39% (95% Credible Intervals (CrI): 2.79, 3.97) and 0.97% (95% CrI: 0.62, 1.36), respectively. After this time, there was a rapid decline in the severity from infection, with the lowest estimated IHR of 0.32% (95% CrI: 0.27, 0.39) in December 2022 and IFR of 0.06% (95% CrI: 0.04, 0.08) in April 2022. We found infection severity to vary more markedly between regions early in the pandemic however, the absolute heterogeneity has since reduced. The risk from infection of SARS-CoV-2 has changed substantially throughout the COVID-19 pandemic with a decline of 86.03% (80.86, 89.35) and 89.67% (80.18, 93.93) in the IHR and IFR, respectively, since early 2021. From April 2022 until March 2023, the end of the ONS CIS study, we found fluctuating patterns in the severity of infection with the resumption of more normative mixing, resurgent epidemic waves, patterns of waning immunity, and emerging variants that have shown signs of convergent evolution. The severity of SARS-CoV-2 infection varied over the course of the pandemic due to factors such as changes in variant characteristics and population immunity from previous infection or vaccination. Here, the authors estimate infection hospitalisation and infection fatality rates in England over time from the start of the pandemic until March 2023. [ABSTRACT FROM AUTHOR]

Evolution is one of the controversial topics in biology primarily because of the perceived conflict between religion and evolution. Religiosity is one of the biggest predictors of evolution acceptance, i.e., the more religious an individual, the less accepting they are of evolution. Most students in the United States are religious, so how evolution is taught in the classroom is essential for a more inclusive experience. However, educators do not have a way to measure what factors influence students' evolution acceptance. We developed a survey instrument with validity evidence called the "predictive Factors of Evolution Acceptance and Reconciliation" (pFEAR). Using this measure, with data from eight religiously affiliated institutions in the United States, educators can understand how their religious and scientific worldview factors influence their students' views on evolution acceptance. Our study showed that religious influence was the most statistically significant predictor of evolution acceptance among religious students by a factor of 2, when compared to students scientific worldviews and the perceived conflict between science and religion. It also showed that perceived conflict between science and religion and being influenced by science were significant positive predictors of evolution acceptance. Further, this study identifies ways educators can use the pFEAR in the classroom to better understand their student's views and better modify how they approach teaching evolution in their classroom. [ABSTRACT FROM AUTHOR]

Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

The rail industry in Australia screens workers for probable obstructive sleep apnea (OSA) due to known safety risks. However, existing criteria to trigger screening only identify a small proportion of workers with OSA. The current study sought to examine the relationship between OSA risk and rail incidents in real-world data from Australian train drivers, and conducted a proof of concept analysis to determine whether more conservative screening criteria are justified. Health assessment (2016–2018) and subsequent rail incident data (2016–2020) were collected from two passenger rail service providers. Predictors included OSA status (confirmed no OSA with a sleep study, controlled OSA, unknown OSA [no recorded sleep assessment data] and confirmed OSA with no indication of treatment); OSA risk according to the current Standard, and OSA risk according to more conservative clinical markers (BMI threshold and cardiometabolic burden). Coded rail safety incidents involving the train driver were included. Data were analysed using zero-inflated negative binomial models to account for over-dispersion with high 0 counts, and rail safety incidents are reported using Incidence Risk Ratios (IRRs). A total of 751 train drivers, typically middle-aged, overweight to obese and mostly men, were included in analyses. There were 43 (5.7%) drivers with confirmed OSA, 62 (8.2%) with controlled OSA, 13 (1.7%) with confirmed no OSA and 633 (84.4%) drivers with unknown OSA. Of the 633 train drivers with unknown OSA status, 21 (3.3%) met 'at risk' criteria for OSA according to the Standard, and incidents were 61% greater (IRR: 1.61, 95% Confidence Interval (CI) 1.02–2.56) in the years following their health assessment compared to drivers who did not meet 'at risk' criteria. A more conservative OSA risk status using lower BMI threshold and cardiometabolic burden identified an additional 30 'at risk' train drivers who had 46% greater incidents compared to drivers who did not meet risk criteria (IRR (95% CI) 1.46 (1.00–2.13)). Our more conservative OSA risk criteria identified more workers, with greater prospective incidents. These findings suggest that existing validated tools could be considered in future iterations of the Standard in order to more sensitively screen for OSA. [ABSTRACT FROM AUTHOR]

Orcs are monsters with origins in Irish folklore popularized in the Lord of the Rings book and movie series, and also widely used in the Dungeons and Dragons (D&D) game systems. In recent years, controversies have arisen regarding whether orcs involve racist depictions or may promote racism in real life. Recent evidence from other studies finds that playing D&D is not associated with real-life racism, and most people including people of color don't find depictions of orcs to be offensive or racist. However, it may still be possible that racist stereotypes are used in visual depictions of orcs. The current study sought to address this with a content analysis of 78 images of orcs from the D&D game or from the Lord of the Rings and Hobbit movies from the 1970s and 2000s. Use of racist stereotypes were very rare in visual depictions of orcs and incidental when they did occur. Evidence did not support that visual depictions of orcs depended upon visual stereotypes of real-life human groups. [ABSTRACT FROM AUTHOR]

Purpose: Statins are commonly prescribed medications with recognised side effects including muscle weakness. Despite this, little is known about their effect on the physical activity and falls risk in the older population. This paper aims to explore the relationship between statin use and the physical activity and falls risk in adults aged 65 and older. Methods: MEDLINE, Embase, CINAHL and PsycINFO were searched on 21/11/2022 to obtain relevant articles. Data considered appropriate included that relating to muscle strength, grip strength, gait speed, balance and falls incidence. Reference and citation searches were performed to identify further relevant papers, and all eligible articles were subject to a Critical Appraisal Skills Programme (CASP) to assess potential bias. With the data being highly heterogeneous, no attempt to measure effect size was made and a narrative synthesis approach was used. The review proposal was registered with PROSPERO: CRD42022366159. Results: Twenty articles were included. Data were inconsistent throughout, with the overall trend suggesting no significant negative effects of statins on the parameters of physical activity, or on falls risk. This was especially true in matched and adjusted cohorts, where potential confounders had been accounted for. Conclusion: This review did not identify a relationship between statin use and physical activity and falls risk in people aged 65 years and older. Ultimately, the risks and benefits of every medication should be considered in the context of each individual. [ABSTRACT FROM AUTHOR]

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm. Current guidelines recommend stereotactic radiosurgery for brain metastasis measuring less than 3 cm but there is significant variability in outcomes following treatment. This study shows that in treatment naïve brain metastasis less than 3 cm, intrinsic biological differences across multiple histologies may influence response to stereotactic radiosurgery. [ABSTRACT FROM AUTHOR]

External spacecraft materials play an important role in satellite protection from the harsh space environment.Research has shown that the physical, chemical, and optical properties of matter change continuously as a result of exposure to solar radiation and aggressive chemical species produced in Earth's upper atmosphere. Thorough knowledge of the material properties evolution throughout a planned mission lifetime helps to improve the reliability of spacecraft. Moreover, the establishment of correlation factors between true space exposure and accelerated space weather experiments at ground facilities enables accurate prediction of on-orbit material performance based on laboratory-based testing. The presented work evaluates the radiation effects of different doses of high-energy electron exposure on surface morphology, optical, and charge transport properties of two materials from the PET family, Melinex®454 and Mylar®M021. [ABSTRACT FROM AUTHOR]

Background: 5-Fluorouracil (5-FU) remains a core component of systemic therapy for colorectal cancer (CRC). However, response rates remain low, and development of therapy resistance is a primary issue. Combinatorial strategies employing a second agent to augment the therapeutic effect of chemotherapy is predicted to reduce the incidence of treatment resistance and increase the durability of response to therapy. Methods: Here, we employed quantitative proteomics approaches to identify novel druggable proteins and molecular pathways that are deregulated in response to 5-FU, which might serve as targets to improve sensitivity to chemotherapy. Drug combinations were evaluated using 2D and 3D CRC cell line models and an ex vivo culture model of a patient-derived tumour. Results: Quantitative proteomics identified upregulation of the mitosis-associated protein Aurora B (AURKB), within a network of upregulated proteins, in response to a 24 h 5-FU treatment. In CRC cell lines, AURKB inhibition with the dihydrogen phosphate prodrug AZD1152, markedly improved the potency of 5-FU in 2D and 3D in vitro CRC models. Sequential treatment with 5-FU then AZD1152 also enhanced the response of a patient-derived CRC cells to 5-FU in ex vivo cultures. Conclusions: AURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC. [ABSTRACT FROM AUTHOR]

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. [ABSTRACT FROM AUTHOR]

Although the work of G.F.C. Griss is commonly understood as a program of negationless mathematics, close examination of Griss's work suggests a more fundamental feature is its executability, a requirement that mental constructions are possible only if corresponding mental activity can be actively carried out. Emphasizing executability reveals that Griss's arguments against negation leave open several types of negation—including D. Nelson's strong negation—as compatible with Griss's intuitionism. Reinterpreting Griss's program as one of executable mathematics, we iteratively develop a pair of bilateral constructive logics and argue for their adequacy as accounts of the propositional basis of Griss's work. We conclude by observing connexive features exhibited by the two bilateral logics and by investigating the difficulties connexive principles reveal for the development of executable mathematics. [ABSTRACT FROM AUTHOR]

Introduction: High-intensity interval training (HIIT) and sprint interval training (SIT) consistently elevate post-exercise metabolism compared to moderate-intensity continuous training (MICT) in young adults (18–25 years), however few studies have investigated this in middle-aged adults. Purpose: To assess the effect of exercise intensity on post-exercise metabolism following submaximal, near-maximal, and supramaximal exercise protocols in middle-aged adults. Methods: 12 participants (8 females; age: 44 ± 10 years; V ˙ O2max: 35.73 ± 9.97 mL·kg−1 min−1) had their oxygen consumption ( V ˙ O2) measured during and for 2 h following 4 experimental sessions: (1) no-exercise control (CTRL); (2) MICT exercise (30 min at 65% V ˙ O2max); (3) HIIT exercise (10 × 1 min at 90% maximum heart rate with 1 min rest); and (4) modified-SIT exercise (8 × 15 s "all-out" efforts with 2 min rest). Between session differences for V ˙ O2 and fat oxidation were compared. Results: O2 consumed post-exercise was elevated during the 1st h and 2nd h following HIIT (15.9 ± 2.6, 14.7 ± 2.3 L; P < 0.036, d > 0.98) and modified-SIT exercise (16.9 ± 3.3, 15.30 ± 3.4 L; P < 0.041, d > 0.96) compared to CTRL (13.3 ± 1.9, 12.0 ± 2.5 L) while modified-SIT was also elevated vs HIIT in the 1st h (P < 0.041, d > 0.96). Total post-exercise O2 consumption was elevated following all exercise sessions (MICT: 27.7 ± 4.1, HIIT: 30.6 ± 4.8, SIT: 32.2 ± 6.6 L; P < 0.027, d > 1.03) compared to CTRL (24.9 ± 4.1 L). Modified-SIT exercise increased fat oxidation (0.103 ± 0.019 g min−1) compared to all sessions post-exercise (CTRL: 0.059 ± 0.025, MICT: 0.075 ± 0.022, HIIT: 0.081 ± 0.021 g·min−1; P < 0.007, d > 1.30) and HIIT exercise increased compared to CTRL (P = 0.046, d = 0.87). Conclusion: Exercise intensity has an important effect on post-exercise metabolism in middle-aged adults. [ABSTRACT FROM AUTHOR]

The study compares the three deep learning approaches and assesses their relative performance solving the 1-D magnetotellurics (MT) inverse problem. MT data from a 1-D geothermal-type structure are used as an example to examine Variational Autoencoder (VAE), Residual Network (Res-Net), and U-Net architectures, adapted for 1-D MT inversion. Root Mean Square Error (RMSE) and Pearson correlation coefficient are applied as misfit measure and similarity criterion, and box plot tools are used to parameterize individual model parameters. The results show that the U-Net provides the most successful recovery of the 1-D resistivity models, even though all three approaches can produce accurate inversions of MT data. To investigate applicability of results to real data sets, the models performance are examined for the case of data containing noise. Three deep learning algorithms are robust with respect to data noise, although the U-Net is relatively superior. The study results provide a platform for more complex magnetotelluric inverse problems and ones involving real data sets. [ABSTRACT FROM AUTHOR]

The affect misattribution procedure (AMP) is a measure of implicit evaluations, designed to index the automatic retrieval of evaluative knowledge. The AMP effect consists in participants evaluating neutral target stimuli positively when preceded by positive primes and negatively when preceded by negative primes. After multiple prior tests of intentionality, Hughes et al. (Behav Res Methods 55(4):1558–1586, 2023) examined the role of awareness in the AMP and found that AMP effects were larger when participants indicated that their response was influenced by the prime than when they did not. Here we report seven experiments (six preregistered; N = 2350) in which we vary the methodological features of the AMP to better understand this awareness effect. In Experiments 1–4, we establish variability in the magnitude of the awareness effect in response to variations in the AMP procedure. By introducing further modifications to the AMP procedure, Experiments 5–7 suggest an alternative explanation of the awareness effect, namely that awareness can be the outcome, rather than the cause, of evaluative congruency between primes and responses: Awareness effects emerged even when awareness could not have contributed to AMP effects, including when participants judged influence awareness for third parties or primes were presented post hoc. Finally, increasing the evaluative strength of the primes increased participants' tendency to misattribute AMP effects to the influence of target stimuli. Together, the present findings suggest that AMP effects can create awareness effects rather than vice versa and support the AMP's construct validity as a measure of unintentional evaluations of which participants are also potentially unaware. [ABSTRACT FROM AUTHOR]

Introduction: The Veterans Health Administration (VHA) distributes video-enabled tablets to individuals with barriers to accessing care. Data suggests that many tablets are under-used. We surveyed Veterans who received a tablet to identify barriers that are associated with lower use, and evaluated the impact of a telephone-based orientation call on reported barriers and future video use. Methods: We used a national survey to assess for the presence of 13 barriers to accessing video-based care, and then calculated the prevalence of the barriers stratified by video care utilization in the 6 months after survey administration. We used multivariable modeling to examine the association between each barrier and video-based care use and evaluated whether a telephone-based orientation modified this association. Results: The most prevalent patient-reported barriers to video-based care were not knowing how to schedule a visit, prior video care being rescheduled/canceled, and past problems using video care. Following adjustment, individuals who reported vision or hearing difficulties and those who reported that video care does not provide high-quality care had a 19% and 12% lower probability of future video care use, respectively. Individuals who reported no interest in video care, or did not know how to schedule a video care visit, had an 11% and 10% lower probability of being a video care user, respectively. A telephone-based orientation following device receipt did not improve the probability of being a video care user. Discussion: Barriers to engaging in virtual care persist despite access to video-enabled devices. Targeted interventions beyond telephone-based orientation are needed to facilitate adoption and engagement in video visits. [ABSTRACT FROM AUTHOR]

Shift work, involving night work, leads to impaired sleep, cognition, health and wellbeing, and an increased risk of occupational incidents. Current countermeasures include circadian adaptation to phase shift circadian biomarkers. However, evidence of real-world circadian adaptation is found primarily in occupations where light exposure is readily controlled. Despite this, non-photic adaptation to shift work remains under researched. Other markers of shift work adaptation exist (e.g., improvements in cognition and wellbeing outcomes) but are relatively unexplored. Timeframes for shift work adaptation involve changes which occur over a block of shifts, or over a shift working career. We propose an additional shift work adaptation timeframe exists which encompasses acute within shift changes in markers of adaptation. We also propose that physical activity might be an accessible and cost-effective countermeasure that could influence multiple markers of adaptation across three timeframes (Within Shift, Within Block, Within Work-span). Finally, practical considerations for shift workers, shift work industries and future research are identified. This Perspective proposes that shift work adaptation occurs within-shift, over a block of shifts, or over a shift working career and offers physical activity as an accessible countermeasure to support adaptation across these timeframes. [ABSTRACT FROM AUTHOR]

Purpose: Pathogen transmission during cardio-pulmonary exercise testing (CPET) is caused by carrier aerosols generated during respiration. Methods: Ten healthy volunteers (age range: 34 ± 15; 4 females) were recruited to see if the physiological reactions to ramp-incremental CPET on a cycle ergometer were affected using an in-line filter placed between the mouthpiece and the flow sensor. The tests were in random order with or without an in-line bacterial/viral spirometer filter. The work rate aligned, time interpolated 10 s bin data were compared throughout the exercise period. Results: From rest to peak exercise, filter use increased only minute ventilation ( V ˙ E) (Δ V ˙ E = 1.56 ± 0.70 L/min, P < 0.001) and tidal volume (VT) (ΔVT = 0.10 ± 0.11 L, P = 0.014). Over the entire test, the slope of the residuals for V ˙ CO2 was positive (0.035 ± 0.041 (ΔL/L), P = 0.027). During a ramp-incremental CPET in healthy subjects, an in-line filter increased V ˙ E and VT but not metabolic rate. Conclusion: In conclusion, using an in-line filter is feasible, does not affect appreciably the physiological variables, and may mitigate risk of aerosol dispersion during CPET. [ABSTRACT FROM AUTHOR]