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BACKGROUND RESULTS CONCLUSION Mango fruits undergo numerous postharvest quality losses during storage. Hence, the present study aimed to increase the shelf life of mango fruits by applying hexanal‐based enhanced freshness formulations (EFF) in combination with hot water treatment (HWT).The findings revealed that, among all the tested applications, the combination of EFF 1.0% + HWT reduced the weight loss, decay incidence, and activity of cell wall degrading enzymes of mango fruits. Also, the combined treatment was effective in maintaining the fruit quality parameters such as soluble solid contents, titratable acidity, ascorbic acid and activity of antioxidant compounds.The present study concludes that the postharvest application of EEF 1.0% in combination with HWT can be used in extending the shelf life of mango cv. ‘Langra,’ fruits stored at 12° C and 85–90% relative humidity for 35 days. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (SM) bloodstream infections (BSIs) contribute to significant mortality in hematologic malignancy (HM) and hematopoietic stem cell transplantation (HSCT) patients. A risk score to predict SM BSI could reduce time to appropriate antimicrobial therapy (TTAT) and improve patient outcomes. A single center cohort study of hospitalized adults with HM/HSCT was conducted. Patients had ≥ 1 blood culture with a Gram-negative (GN) organism. A StenoSCORE was calculated for each patient. The StenoSCORE2 was developed using risk factors for SM BSI identified via logistic regression. Receiver operating characteristic (ROC) curves were plotted. Sensitivity and specificity for the StenoSCORE and StenoSCORE2 were calculated. Thirty-six SM patients and 534 non-SM patients were assessed. A StenoSCORE ≥ 33 points was 80% sensitive, 68% specific, and accurately classified 69% of GN BSIs. StenoSCORE2 variables included acute leukemia, prolonged neutropenia, mucositis, ICU admission, recent meropenem and/or cefepime exposure. The StenoSCORE2 performed better than the StenoSCORE (ROC AUC 0.84 vs. 0.77). A StenoSCORE2 ≥ 4 points was 86% sensitive, 76% specific, and accurately classified 77% of GN BSIs. TTAT was significantly longer for patients with SM BSI compared with non-SM BSI (45.16 h vs. 0.57 h; p < 0.0001). In-hospital and 28-day mortality were significantly higher for patients with SM BSI compared to non-SM BSI (58.3% vs. 18.5% and 66.7% vs. 26.4%; p-value < 0.0001). The StenoSCORE and StenoSCORE2 performed well in predicting SM BSIs in patients with HM/HSCT and GN BSI. Clinical studies evaluating whether StenoSCORE and/or StenoSCORE2 implementation improves TTAT and clinical outcomes are warranted. [ABSTRACT FROM AUTHOR]

Tea is being grown on the gentle slopes of Himachal Pradesh located in the north-western region of mighty Himalaya, since 1850s. However, degrading soil health due to rampant usage of agrochemicals, and long-run tea cultivation adversely affects the productivity potential of the region. Analyzing soil-nutrient status is of great value to meet the crop nutrient demand. The research aimed to identify the vulnerable soil properties and their assessment for soil restoration under major tea estates of the North-western Himalaya. The study examined the physico-chemical and biological properties of soils of 37 tea estates. The large variation among different sites for physical parameters signifies the textural difference between the sites under study. Meanwhile, the soil pH of tea estates varied from extremely acidic to slightly acidic reaction, with an overall pH (H2O) of 5.33 in the top soils and 5.47 in the subsoils. High OC (13.35 g kg−1) under overall soil depth of tea estates presumably correlated with higher concentration of available nutrients, i.e. N (r = 0.641), K (r = 0.492), and S (r = 0.623) alongside exchangeable Ca (r = 0.724) and Mg (r = 0.718). The substrate carbon availability due to higher amount of organic matter in the top soils (16.1 g kg−1) leads to increased biological activity (MBC and DHA) in the surface soils as compared to subsoils. The unscientific approach of fertilizer application led to huge variability in green leaf yield across different tea estates. Thus, to achieve higher yield, it should be necessary to adopt nutrient application in a judicial manner in the tea plantations. [ABSTRACT FROM AUTHOR]

Tissue buckling is an increasingly appreciated mode of morphogenesis in the embryo, but it is often unclear how geometric and material parameters are molecularly determined in native developmental contexts to generate diverse functional patterns. Here, we study the link between differential mechanical properties and the morphogenesis of distinct anteroposterior compartments in the intestinal tract--the esophagus, small intestine, and large intestine. These regions originate from a simple, common tube but adopt unique forms. Using measured data from the developing chick gut coupled with a minimal theory and simulations of differential growth, we investigate divergent lumen morphologies along the entire early gut and demonstrate that spatiotemporal geometries, moduli, and growth rates control the segment-specific patterns of mucosal buckling. Primary buckling into wrinkles, folds, and creases along the gut, as well as secondary buckling phenomena, including period-doubling in the foregut and multiscale creasing-wrinkling in the hindgut, are captured and well explained by mechanical models. This study advances our existing knowledge of how identity leads to form in these regions, laying the foundation for future work uncovering the relationship between molecules and mechanics in gut morphological regionalization. [ABSTRACT FROM AUTHOR]

• Perceptions of pedestrian safety interacting with self- vs. human-driven vehicles. • Deception experiment to measure implicit attitudes (Autonomy Bias). • Autonomy Bias exists, is negative on average, and varies widely across individuals. • Autonomy Bias is more related to technological orientation than socio-demographics. • Implicit and explicit attitudes are strongly related but distinct. Ensuring comfort and safety for pedestrians is essential to the responsible introduction of automated or self-driving vehicles (SDV). Few studies have attempted to isolate the effect of vehicle automation on perceptions of pedestrian interactions with SDV, separate from the potentially confounding effects of vehicle operation or appearance, and we still have limited understanding of the explicit and implicit attitudes mediating those perceptions. The objectives of this study are to determine 1) if there is an "Autonomy Bias" in the population of British Columbia, Canada (i.e., whether people perceive pedestrian-SDV interactions as inherently more or less comfortable and safe than otherwise equivalent interactions with human-driven vehicles or HDV), and if so, 2) which personal attributes influence Autonomy Bias. We isolate the effect of vehicle autonomy on perceptions using a novel deception-based experiment in which 1,133 participants rate 8 video clips of pedestrian interactions in a crosswalk; all clips show HDV, but a random half of the videos for each participant are described as SDV. Results show that Autonomy Bias varies widely across the population, with a small but significantly (p < 0.05) negative mean value (i.e., SDV interactions are perceived as less comfortable and safe). To ensure that an average person is as comfortable crossing with SDV as they currently are with HDV (i.e., to offset their Autonomy Bias), SDV must allow at least 0.4 s additional passing time at crosswalks; at least 3.7 s additional time is needed to ensure equivalent comfort for 85 % of the population. The implicit attitude of Autonomy Bias is strongly related to but distinct from explicit, self-reported attitudes toward technology and SDV, and may improve with SDV familiarity. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is a common surgery for osteoarthritis, with increasing prevalence expected in the near future. This systematic review and meta‐analysis compared the effectiveness of computerized TKA versus traditional TKA, focusing on postoperative outcomes measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and the Knee Society score (KSS). A search on PubMed and Cochrane databases on November 14, 2023 for retrospective randomized controlled trials (RCTs) yielded data on WOMAC and KSS. The search strategy was predefined, and methodological quality of studies was critically appraised. Two researchers extracted data. Unpaired t‐testing assessed the mean monthly changes in KSS and WOMAC for computer‐aided versus traditional TKA. Review Manager 5.3 was used for data synthesis and analysis. Out of 729 records, five RCTs enrolling 339 patients were eligible and analyzed using a random effects meta‐analysis. The mean monthly ΔKSS score differed significantly between the traditional and computerized groups (11.47 ± 8.76 vs. 9.26 ± 6.05, respectively; p < 0.01). However, the pooled mean difference estimate showed no significant differences (D = 0.20, 95% CI = −0.53 to 0.93, p = 0.59), with high heterogeneity (I2 = 85%, p < 0.001). The mean monthly ΔWOMAC score also differed significantly (−14.18 ± 21.54 vs. −18.43 ± 20.65, respectively; p < 0.05), but again, no significant differences were found in the pooled estimate (D = 0.17, 95% CI = −0.46 to 0.79, p = 0.60), with moderate heterogeneity (I2 = 28%, p = 0.24).There is no significant difference in KSS or WOMAC outcomes between traditional and computerized TKA. The study suggests the need for further research with longer follow‐up periods, more timepoints, and a broader range of patient outcome measures to fully evaluate the advantages and disadvantages of each method. [ABSTRACT FROM AUTHOR]

Olfactory oscillations may enhance cognitive processing through coupling with beta (β, 15–30 Hz) and gamma (γ, 30–160 Hz) activity in the hippocampus (HPC). We hypothesize that coupling between olfactory bulb (OB) and HPC oscillations is increased by cholinergic activation in control rats and is reduced in kainic‐acid‐treated epileptic rats, a model of temporal lobe epilepsy. OB γ2 (63–100 Hz) power was higher during walking and immobility‐awake (IMM) compared to sleep, while γ1 (30–57 Hz) power was higher during grooming than other behavioral states. Muscarinic cholinergic agonist pilocarpine (25 mg/kg ip) with peripheral muscarinic blockade increased OB power and OB‐HPC coherence at β and γ1 frequency bands. A similar effect was found after physostigmine (0.5 mg/kg ip) but not scopolamine (10 mg/kg ip). Pilocarpine increased bicoherence and cross‐frequency coherence (CFC) between OB slow waves (SW, 1–5 Hz) and hippocampal β, γ1 and γ2 waves, with stronger coherence at CA1 alveus and CA3c than CA1 stratum radiatum. Bicoherence further revealed a nonlinear interaction of β waves in OB with β waves at the CA1‐alveus. Beta and γ1 waves in OB or HPC were segregated at one phase of the OB‐SW, opposite to the phase of γ2 and γ3 (100–160 Hz) waves, suggesting independent temporal processing of β/γ1 versus γ2/γ3 waves. At CA1 radiatum, kainic‐acid‐treated epileptic rats compared to control rats showed decreased theta power, theta‐β and theta‐γ2 CFC during baseline walking, decreased CFC of HPC SW with γ2 and γ3 waves during baseline IMM, and decreased coupling of OB SW with β and γ2 waves at CA1 alveus after pilocarpine. It is concluded that β and γ waves in the OB and HPC are modulated by a slow respiratory rhythm, in a cholinergic and behavior‐dependent manner, and OB‐HPC functional connectivity at β and γ frequencies may enhance cognitive functions. [ABSTRACT FROM AUTHOR]

Background: Low sperm motility, one of the common causes of male infertility, is associated with abnormal sperm quality. Currently, important sperm/semen biomarkers are sperm chromatin status and oxidation‒reduction potential (ORP) in semen. Because the association between sperm motility and these biomarkers is still not fully clarified, our study was designed to verify the distribution and risk of sperm DNA fragmentation (SDF) and oxidative stress in semen in asthenozoospermic men. Materials and methods: This study was carried out on discharged sperm cells of asthenozoospermic men (isolated asthenozoospermia or coexisted with reduced sperm number and/or morphology), nonasthenozoospermic men (reduced total sperm count and/or sperm morphology) (experimental groups) and normozoospermic men (proven and presumed fertility) (control group). Basic semen analysis was evaluated according to the 6th edition of the World Health Organization manual guidelines. SDF was assessed using the sperm chromatin dispersion test, while static(s) ORP in semen was measured by means of a MiOXSYS analyser. Results: The men from the asthenozoospermic group had lower basic semen parameters than those from the control and nonasthenozoospermic groups. In men with poor sperm motility SDF and sORP, prevalence and risk for > 20% SDF (high level of DNA damage) and for > 1.37 sORP (oxidative stress) were significantly higher than those of control and nonasthenozoospermic subjects. The risk for sperm DNA damage and oxidative stress in asthenozoospermic men was over 10‐fold higher and almost 6‐fold higher than those in control subjects and almost or over 3‐fold higher than those in nonasthenozoospermic men. Conclusions and discussion: Poor human sperm motility coexisted with low basic sperm quality. Sperm DNA damage and oxidative stress in semen were much more frequent in asthenozoospermia. These abnormalities can decrease the sperm fertilizing capability under both natural and medically assisted reproduction conditions. Thus, in asthenozoospermia, the evaluation of sperm chromatin status and oxidation–reduction potential in semen is justified and inevitable, and the appropriate antioxidant therapy can be suggested. [ABSTRACT FROM AUTHOR]

The parametric and traditional CAD approaches are fundamental for pattern construction. This paper empirically analyses their geometric data entry, construction space, methods, workflow, and outputs, highlighting differences between the two. The results show that the traditional approach offers faster data entry but lacks editability, while the parametric approach prioritizes data modification efficiency despite requiring more time for initial entry. The traditional approach allows quicker construction but becomes time-consuming for significant pattern changes, whereas the parametric approach, although slower to construct, offers editable blocks for efficient modification. The parametric approach captures both geometric shapes and block logic, in contrast to the traditional approach's focus solely on geometric shapes. The parametric approach supports the creation of custom garments, reducing waste and promoting sustainability, while the traditional approach leads to static blocks necessitating recreation for each new wearer. Accordingly, educational institutions should spearhead the transition to the parametric approach. [ABSTRACT FROM AUTHOR]

We continue our investigation of binary actions of simple groups. In this paper, we demonstrate a connection between the graph Γ ⁢ ( C ) \Gamma(\mathcal{C}) based on the conjugacy class 풞 of the group 퐺, which was introduced in our previous work, and the notion of a strongly embedded subgroup of 퐺. We exploit this connection to prove a result concerning the binary actions of finite simple groups that contain a single conjugacy class of involutions. [ABSTRACT FROM AUTHOR]

This study explores the instructional implications of using podcasts framed by a critical media literacy framework in a high school social justice classroom. This 10‐week, critical media‐framed study examines how eight 16–18‐year‐old students, taught synchronously on Zoom, engaged in weekly podcast‐based lesson activities, selecting podcast episodes as supplemental course texts related to the current classroom topics of study (two episodes per unit topic). Findings indicate that podcasts opened spaces for students to hear various voices, particularly marginalized narratives on controversial topics. Additionally, by engaging in critical media literacy practices, students' own voices were elevated, and students questioned the role of texts in their understanding of the world around them. These findings are of particular value to educators looking to understand the classroom implications of critical media literacy practices and who want to provide counter‐hegemonic narratives in their classrooms. [ABSTRACT FROM AUTHOR]

Previous research has indicated the suitability of behavioural activation (BA) as an intervention for reducing depression in older adults. However, little research has investigated the potential of BA to increase active engagement and well-being in older adults. The current pilot study sought to investigate the usefulness and acceptability of BA to promote well-being in a group of non-clinical older adults. Participants (N = 18) aged between 65 and 86 (M = 77.82, SD = 5.59) who were retired and living independently in the community were provided a 6-week BA program predominantly delivered online. Treatment retention, self-ratings, and participants' compliance to treatment principles indicate preliminary feasibility for the use of BA as an approach for increasing active engagement in older adult populations. Participants also provided feedback on their experiences with the program post-intervention via individual structured interviews. Thematic analysis of these data revealed that participants found the program to be beneficial in terms of increased self-awareness and social engagement, and provided several recommendations for improving acceptability of the program and workbook. The unexpected events relating to the first wave of the novel coronavirus (COVID-19) led to necessary adaptations to delivery modalities, and provided the researchers with an opportunity to investigate the use of a structured well-being program on a high-risk population during a pandemic. Our findings support the proposition that BA is a suitable intervention for increasing engagement and well-being in older adults, provide insight into adapting programs for older adults, and suggest next steps for testing intervention efficacy. [ABSTRACT FROM AUTHOR]

Background and aims Design, setting and participants Measurements Findings Conclusions With the prevalence of e‐cigarette use among Australian youth increasing significantly in recent years, greater attention is being paid to encouraging and supporting cessation. However, research to inform such efforts is lacking. The present study sought to (i) measure desire to quit e‐cigarette use and actual quitting attempts among young Australians and (ii) explore correlates of quitting‐related cognitions and behaviours.This was a cross‐sectional on‐line survey conducted in Australia. The participants were 14−25‐year‐old e‐cigarette users (n = 602; 53% women).Desire to quit vaping and attempts to quit vaping were the primary dependent variables. The independent variables included several individual (e.g. harm perceptions, perceived appeal of vapes), social (descriptive norms) and environmental (e.g. ease of e‐cigarette access) factors.A majority of respondents (61%) expressed a desire to quit vaping, and just over half (55%) had made a quit attempt. Finding vapes easy to access was associated with both a lack of desire [odds ratio (OR) = 0.71] and attempts to quit (OR = 0.77), while self‐reported addiction to vaping (OR = 1.42 and OR = 3.11) and perceiving vaping to be associated with mental health risks (OR = 1.30 and OR = 1.40) were positively correlated with these variables. Perceiving that vaping is common among people of one’s age (OR = 0.82) and finding vapes appealing (OR = 0.55) were associated with a lack of desire to quit, while perceiving vaping to have physical health risks was positively associated with quitting desire (OR = 1.58). School‐based education on vaping was associated with reporting an attempt/s to quit (OR = 0.47).This survey of young Australian e‐cigarette users suggests a high level of desire to quit using e‐cigarettes and attempts to quit. Increasing knowledge regarding the physical and mental health risks associated with e‐cigarette use may assist with promoting quitting‐related intentions. Changing social norms, reducing the accessibility of e‐cigarettes and reducing the appeal of the products also constitute potential means of increasing the desire to quit. [ABSTRACT FROM AUTHOR]

The mainstream media and local health campaigns in Singapore racialize heart health disparities. Journalists and campaigners report differences in heart health outcomes from a model of race governance known as the Chinese, Malay, Indian, and Others (CMIO) model. This model is then used to frame heart health inequities as an outcome of poor cultural practices and behaviors tied to race. To (un)do the racializing frames of heart health as outcomes of cultural behaviors and practices, I instead center stories of heart health management by Malay participants from lower-income households, identifying the role information asymmetries play in incomplete heart health information retrieval during interactions with providers (social service providers, healthcare workers, doctors, nurses). Cultural and community resources were discussed as critical resources for alleviating urgent heart health episodes or assisting as guides for preventative heart health information. Health campaigners must delve deeper into these findings for more structurally responsive heart health interventions and move away from racializing health disparities based on the CMIO model. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 swiftly spread in Wuhan, China, leading to a pandemic crisis worldwide. Genome sequence analysis of this virus revealed a close analogy with its closely related strains, SARS-COV and MERS-COV. In the case of SARS-CoV-2, Nonstructural protein 13 (NSP13), also known as helicase, has been identified as a target for reducing the severity of infection due to its high sequence conservation and essential role in viral replication. NSP13 helicase structure in SARS-CoV-2 differs only by one amino acid from the SARS-CoV helicase structure. Targeting NSP13 with natural compounds holds significant potential for developing safe and effective antiviral therapies utilizing advanced computational approaches. The properties of 8 different natural compounds, i.e. Imidazole, Pyrrole, Tropolone, Benzotriazole, Imidazodiazepine, Phenothiazine, Acridone and Bananin were screened by applying Lipinski's rule of five, ADME (absorption, distribution, metabolism, and excretion) properties, and Radar plots to discover their drug efficacy at a target site, safety, and absorption. Docking studies confirmed Bananin with a binding affinity of -7 kcal/mol as a potential inhibitor of NSP13 of SARS-CoV-2 with better pharmacokinetics, drug likeliness, and oral bioavailability. Based on the in silico study, it is suggested that Bananin shows promising effects against NSP13 protein, forming a maximum number of hydrogen bonds exhibiting higher binding affinity. This stronger affinity indicates a stronger interaction between the compound and its target, potentially leading to enhanced biological activity and therapeutic efficacy. This novel study has unlocked the door for a prospective SARS-CoV-2 inhibition strategy and developing antiviral interventions targeting NSP13 based on molecular docking. [ABSTRACT FROM AUTHOR]

This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by facilitating drug transport across the blood–brain barrier. Despite substantial advancements in targeted delivery and vaccine efficacy, challenges remain in scalability, regulatory approval, and transitioning from preclinical studies to clinical applications. The future of chitosan-based nanomedicines hinges on advancing clinical trials, fostering interdisciplinary collaboration, and innovating in nanoparticle design to overcome these hurdles and realize their therapeutic potential. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Intensive rehabilitation aims to improve and maintain functioning in young people who experience disability due to illness or injury. Day rehabilitation may have advantages for families and healthcare systems over inpatient models of rehabilitation. METHODS: This study evaluated the goals and outcomes of a cohort of young people in Western Australia who attended a specialist intensive day rehabilitation programme ("iRehab") at Perth Children's Hospital. Analysis of the iRehab service database was performed. Rehabilitation goals and outcomes were recorded as per the Canadian Occupational Performance Measure (COPM), Children's Functional Independence Measure (WeeFIM), and Goal Attainment Scale (GAS). RESULTS: There were 586 iRehab admissions between August 11, 2011, and December 31, 2018. Admissions were divided by diagnosis: Cerebral Palsy (228, 38.5%), Acquired Brain Injury (125, 21.3%), Spinal Cord Disorders (91, 15.5%), and Other (141, 24.2%). Mean COPM Performance increased by 2.78 points from admission to discharge (95% CI 2.58 to 2.98, p < 0.001). Mean COPM Satisfaction was 3.29 points higher at discharge than admission (95% CI 3.07 to 3.51, p < 0.001). Mean total WeeFIM score improved by 6.51 points between admission and discharge (95% CI 5.56 to 7.45, p < 0.001), and by 3.33 additional points by six months post discharge (95% CI 2.14 to 4.53, p < 0.001). Mean GAS T-scores increased by 27.85 (95% CI 26.73 to 28.97, p < 0.001) from admission to discharge, and by 29.64 (95% CI 28.26 to 31.02, p < 0.001) from admission to six months post discharge, representing improvement consistent with team expectations. CONCLUSION: This study describes a model by which intensive rehabilitation can be delivered in a day rehabilitation setting. A diverse population of young people who experienced disability achieved significant improvements in occupational performance, independence, and goal attainment after accessing intensive day rehabilitation. Improvements were measured in all diagnostic subgroups and were maintained six months after discharge. [ABSTRACT FROM AUTHOR]

The long‐term conservation of species at risk relies on numerous, and often concurrent, management actions to support their recovery. Generally, these actions are habitat‐based while others are focused on a species' position within its ecological community. Less studied are the impacts from human presence, despite evidence that human activity may reduce the area functionally available for occupancy or resource acquisition. In the winter of 2020/2021, COVID‐19‐related travel restrictions led to a reduction in helicopter‐assisted back‐country skiing (heli‐skiing). We examined how these reductions in heli‐skiing (termed the anthropause) affected the movement ecology and resource selection of southern mountain caribou (Rangifer tarandus caribou) as compared to two prior years (2018/2019 and 2019/2020) and the following year when heli‐skiing resumed (2021/2022). We found that home‐range size was on average 80–120% larger during the anthropause than in years of normal heli‐ski operations. Movement rates also varied among periods, with movement during the anthropause (11.9 km2/day) being higher than in 2019/2020 (7.8 km2/day) and 2021/2022 (8.7 km2/day), though similar to 2018/2019 (12.2 km2/day). Resource selection among periods did not differ, with caribou consistently selecting old forests, high elevations and gentle terrain. These results suggest that back‐country recreation, specifically heli‐skiing, may be limiting access to resources for southern mountain caribou. This limitation arises through reduced home‐range size within suitable late‐winter habitat, relative to when heli‐skiing is reduced or not occurring – consistent with Encounter Theory. While the demographic effects of reduced home‐range size and movement were not examined here, reduced access to resources likely compounds other stressors known to affect population viability of caribou. The results of this study demonstrate the impact that recreation can have on wildlife and highlight the need to consider heli‐skiing and other forms of recreation when developing recovery plans. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC. Methods We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR–Egger, Contamination Mixture). We used multivariable MR for the mediation analyses. Results Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08–1.24, P -value = 1.4 × 10−5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2–13%) of the association], smoking (31%, 4–57%) and PA (7%, 2–11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA. Conclusions The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI–CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation. [ABSTRACT FROM AUTHOR]

This article delves into the relationship between heritage and decoloniality in Sri Lanka, focusing on the influence of colonialism and external exploitation on society and heritage in South Asia. The authors, who come from diverse backgrounds, share their personal experiences and perspectives on the topic, emphasizing the importance of cross-community conversations and a critical examination of history and heritage. The text also touches on the perception of a new Chinese colonialism in Sri Lanka. The authors argue that the current understanding of heritage in Sri Lanka is rooted in colonial knowledge and institutions, and advocate for questioning and transforming these institutions as part of the decolonization process. They also stress the need for critical thinking and reflection when engaging with colonial institutions and addressing the diverse history of Sri Lanka. [Extracted from the article]

This article examines the role of assessment in schools and the use of data to measure student progress. The authors argue that relying solely on scores and grades is insufficient and propose a more comprehensive approach that includes frequent formative checks and low-stakes retrieval opportunities. They emphasize the importance of clear communication and understanding among teachers and leaders regarding data collection. The article also discusses the challenges and limitations of using data in education, suggesting the use of multiple sources of data and recognizing the strengths and limitations of data. It raises questions about the purpose of data collection and the importance of teachers' day-to-day inferences. The article acknowledges the pressures of accountability and changing expectations, urging educators to prioritize accurate assessments and informed decision-making. [Extracted from the article]

This article examines the application of the intersectionality framework to the Indian statutory institutional environmental public hearing (EPH) process that seeks to promote environmental justice. Intersectionality provides a framework to capture the processes of gender marginalization and exclusion. It critically demonstrates how the required gender participation in the regulatory EPH process is failing rural women in the state of Gujarat, India, thereby exacerbating discrimination and inequality. Building on the researchers' mixed‐methods (quantitative and qualitative) data, the article creates an evidence‐based 'fresh dossier' reflecting the non‐existent or limited participatory involvement of women as valuable stakeholders in the EPH process. Drawing on the evidence of lived experiences creates spaces for women's voices that are excluded from the social system due to dominant powers and institutional structures. We argue that respecting the diversity of interests and identities of rural Gujarati women within the institutionalized public sphere would promote participation and recognition of their knowledge and role as crucial stakeholders. [ABSTRACT FROM AUTHOR]

In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging. Our study elucidates the intricate immunological dynamics of the CD4/Treg axis in frail older adults compared to comparable age-matched healthy older adults. By utilizing publicly available RNA sequencing and single-cell RNA sequencing (scRNAseq) data from peripheral blood mononuclear cells (PBMCs), we identified a specific Treg cell subset and transcriptional landscape contributing to the dysregulation of CD4+ T-cell responses. We explored the molecular mechanisms underpinning Treg dysfunction, revealing that Tregs from frail older adults exhibit reduced mitochondrial protein levels, impairing mitochondrial oxidative phosphorylation. This impairment is driven by the TNF/NF-kappa B pathway, leading to cumulative inflammation. Further, we gained a deeper understanding of the CD4/Treg axis by predicting the effects of gene perturbations on cellular signaling networks. Collectively, these findings highlight the age-related relationship between mitochondrial dysfunction in the CD4/Treg axis and its role in accelerating aging and frailty in older adults. Targeting Treg dysfunction offers a critical basis for developing tailored therapeutic strategies aimed at improving the quality of life in older adults. [ABSTRACT FROM AUTHOR]

This research focuses on enhancing the wear resistance of EN8 steel, commonly used in agricultural implements by applying WC-12Co and WC-10Co-4Cr coatings using the high-velocity oxy-fuel (HVOF) spraying technique. The microstructural characterization, EDS mapping, microhardness, fracture toughness, slurry abrasion, and dry sliding of all coated and uncoated samples were evaluated. Results demonstrate that coated specimens outperform the uncoated EN8 steel in terms of wear resistance. Slurry abrasion tests reveal that the coatings hardness and fracture toughness contribute to their excellent performance. In dry sliding tests, the coated specimens exhibit lower friction coefficients and less mass loss, further emphasizing their better wear resistance. Further, wear mechanisms were found to be different between the materials, with EN8 steel exhibiting ductile wear, primarily due to plastic deformation and chipping, while the coated specimens display brittle wear characteristics, with the detachment of hard coating material and abrasive interactions contributing to wear. [ABSTRACT FROM AUTHOR]

The transition from concentric primary flow to non-tangential secondary flow of blood was investigated using experimental steady shear rheometry and numerical modelling. The aims were to: assess the difference in secondary flow in a Newtonian versus shear-thinning blood analogue; and measure the secondary flow in the blood. Both experiments and numerical modelling showed that the transition from primary to secondary flow was the same in a Newtonian fluid and a shear-thinning blood analogue. Experiments showed whole blood transitioned to secondary flow at lower modified Reynolds numbers than the Newtonian fluid; and transition was haematocrit dependent with higher RBC concentrations transitioning at lower modified Reynolds numbers. These results indicate that modelling blood as a purely shear-thinning fluid does not predict the correct secondary flow fields in whole blood; non-Newtonian effects beyond shear-thinning behaviour are influential, and incorporating effects such as multiphase contributions and viscoelasticity, yield stress and thixotropy is necessary. [ABSTRACT FROM AUTHOR]

This article introduces the concept of 'freelance feminism': a term we use to highlight how a combination of casualised precarious labour and platformised entrepreneurialism constitute a key terrain through which contemporary feminist work is enacted. The article proposes that this term can be a way to understand new formations and constellations of activity which are being shaped in the intersections between precarity, feminism and entrepreneurialism. How, in what ways, and with what consequences are feminist activism and platformised entrepreneurialism becoming entwined? How are new forms of self-promotion, self-branding and precarity shaping feminist cultures? Are entrepreneurial projects more broadly taking on feminist forms and, if so, how can we understand their politics? To explore these issues, the article examines in turn (1) neoliberal, short-term, precarious labour in the cultural industries and its exacerbation during the pandemic, (2) contemporary entrepreneurial 'platformisation' and (3) the increased visibility of feminism in contemporary popular culture. It concludes by introducing the range of articles in the special issue. [ABSTRACT FROM AUTHOR]

We integrate the existing detrital zircon data from multiple modern river sediment samples on Viti Levu, Fiji, with the most current available geological and topographic mapping of the respective river drainage basins to compare detrital populations with potential bedrock sources. The temporal and spatial variations in zircon geochemistry supplement what is known from igneous rocks and confirm the petrological differences between plutonic and volcanic rocks from the Eocene to early Oligocene (Yavuna age, >30 Ma), middle Oligocene to middle Miocene (Wainimala age, 30–12.5 Ma), late Miocene (Colo age, 12.5–6.5 Ma) and latest Miocene (Namosi age, 6.5–5 Ma). The >30 Ma Yavuna-age zircons are restricted to areas that drain the previously mapped Yavuna Group. The 30–12.5 Ma zircons are found across central Viti Levu from west to east, and the 30–15 Ma zircons have distinctively low U/Yb and high Dy/Yb ratios. They are the best radiometric evidence of widespread early to middle Miocene arc magmatism in Fiji that was relatively U-poor. Peak deconvolution of the Colo age zircons from individual basins suggests the following ages for undated or poorly dated plutons from central Viti Levu. The large Mavuvu pluton is probably composed of multiple intrusions in the 12–10 Ma range, the Waiqa pluton is probably ca 10 Ma, and the Noikoro pluton is probably ca 9 Ma. There are zircons from unknown plutonic or volcanic sources between 8 and 7 Ma in western Viti Levu that have distinct Eu/Eu* ratios. We attribute the highest U/Yb ratios in some Colo age zircons to crustal anatexis. Namosi-age zircons are abundant in the Medrausucu Group and can be found scattered across Viti Levu. Detrital zircon samples have aided geological mapping of the tropical and poorly exposed terrain in Fiji and elucidated the magmatic history. Detrital zircons indicate widespread early to middle Miocene arc magmatism across central Viti Levu. Detrital zircon ages have provided further constraints on the ages of 12-9 Ma plutons in central Viti Levu. Detrital zircon ages indicate that there is an unknown igneous source of 8-7 Ma zircons in western Viti Levu. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. Current treatment options are limited to either symptom management or surgery. A promising treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, there remains a gap in knowledge as to whether MSCs from different tissue sources have similar responses to the low pH microenvironment of the IVD and the possible mechanisms governing these responses. To study this, MSCs from three different tissue sources: adipose (adipose‐derived mesenchymal stem cell), bone marrow (bone marrow mesenchymal stem cells), and amnion (amniotic membrane mesenchymal stem cell) were cultured at low pHs representative of IVDD. MSCs were assessed for survival, senescence, apoptosis, metabolic activity, and cytokine release profile. Additionally, western blot was utilized to assess acid sensing ion channel 1 and 3 expression. The results of this study indicated that MSC viability, cell proliferation, senescence, and metabolic activity is negatively affected by low pH and alters MSC cytokine production. This study also demonstrated that MSCs behavior is dependent on tissue source. Understanding how MSC behavior is altered by pH will allow further research aimed at increasing the efficacy of MSC therapy to promote in situ IVD tissue regeneration to combat IVDD. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusion The aim of the present study was to compare a novel tapered, double‐threaded self‐tapping tissue‐Level design implant (TLC) to a well‐established parallel walled tissue‐level (TL) implant in terms of primary and secondary stability over time.Test TLC (n = 10/per timepoint) and control TL (n = 10/per timepoint) implants were placed in the mandible of minipigs and left for submerged healing for 3, 6, and 12 weeks. Maximum insertion torque and implant stability quotient (ISQ) were measured for each implant at placement. Osseointegration and cortical bone maintenance were histologically evaluated by measuring total bone‐to‐implant contact (BIC) and first bone‐to‐implant contact (fBIC).A significantly higher maximum insertion torque was measured for the test implant TLC compared to the control TL implant (57.83 ± 24.73 Ncm and 22.62 ± 23.16 Ncm, respectively; p < .001). The mean ISQ values were comparable between the two implant types (75.00 ± 6.70 for TL compared to 75.40 ± 3.20 for TLC, p = .988). BIC was comparable between both implant types at each of the evaluated time points. The fBIC was found to be significantly more coronal at 12 weeks for the TLC implant compared to the TL implant (0.31 ± 0.83 mm for TLC compared to −0.22 ± 0.85 for TL, p = .027).The novel tapered tissue level design implant showed improved primary stability and an overall improved crestal bone height maintenance compared to the parallel walled design at 12 weeks. [ABSTRACT FROM AUTHOR]

AbstractCompared to studying other forms of illegal violence, terrorism research faces unique data challenges. Notably, consistent police data are generally lacking, victims often have no direct knowledge of attacks and are sometimes killed, and perpetrators are difficult to interview and are often unreliable sources. In the face of these data challenges, the increasing availability of open source data on terrorist attacks and perpetrators has profoundly affected the scientific study of terrorism. Over time, a growing proportion of published academic research on terrorism—especially more heavily quantitative studies—relies on open source data. Moreover, the growing availability of individual-level terrorism data has allowed empirical tests of psychological and social-psychological theories of radicalization. In this paper, we assess the impact of open source data on the study of terrorism. We begin with an overview, providing a brief history of terrorist attack and perpetrator open source data bases. We then consider the major strengths and weaknesses of both types of open source data and suggest ways of countering the weaknesses. We close with observations about the impact of open source data on terrorism research and future opportunities for improvement. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To examine gender differences in Australian football (AF)‐related concussion presentations to EDs in regional Australia.A prospective observational study of patients presenting to 1 of the 10 EDs in Western Victoria, Australia, with an AF‐related concussion was conducted. Patients were part of a larger study investigating AF injuries over a complete AF season, including pre‐season training and practice matches. Information regarding concussion injuries was extracted from patient medical records, including clinical features, concurrent injuries, mechanism and context of injury. Female and male data were compared with chi‐squared and Fisher's exact tests. P < 0.05 was considered significant.From the original cohort of 1635 patients with AF‐related injuries (242 female and 1393 male), 231 (14.1%) patients were diagnosed with concussion. Thirty‐eight (15.7%) females had concussions versus 193 (13.9%) males (P > 0.05). Females over the age of 16 were more likely to be concussed than males in the same age range (females n = 26, 68.4% vs males n = 94, 48.7%; P = 0.026). Neurosurgically significant head injury was rare (one case). Similar rates of concurrent injury were found between females 15 (39.5%) and males 64 (33.2%), with neck injury the single most common in 24 (10.3%) concussions. Sixty‐nine patients (29%) were admitted for observation or to await the results of scans. The majority of concussions occurred in match play (87.9%). Females were more likely injured in contested ball situations (63.2% vs 37.3%; P < 0.05).Concussion rates for community‐level AF presentations to regional EDs were similar between genders. Serious head injury was rare, although hospital admission for observation was common. Concurrent injuries were common, with associated neck injury most often identified. Match play accounted for the majority of head injuries. [ABSTRACT FROM AUTHOR]

Human activities are causing taxonomic rearrangements across ecosystems that often result in the emergence of novel communities (assemblies with no historical representative). It is commonly assumed that these changes in the taxonomic makeup of ecosystems also inevitably lead to changes in other aspects of biodiversity, namely functional and phylogenetic diversity. However, this assumption is not always valid, as the changes in functional and phylogenetic composition resulting from taxonomic shifts depend on the level of redundancy in the evaluated community. Therefore, we need improved theoretical frameworks to predict when we can expect coordinated or decoupled responses among these three facets of biodiversity. To advance this understanding, we discuss the conceptual and methodological issues that complicate establishing a link between taxonomic rearrangements driven by human activities and the associated functional and phylogenetic changes. Here, we show that is crucial to consider the expected changes in functional and phylogenetic composition as communities are reshaped owing to human drivers of biodiversity loss to forecast the impacts of novel assemblages on ecosystem functions and the services they provide to humanity. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'. [ABSTRACT FROM AUTHOR]

Background: Remote forms of breastfeeding support, such as helplines and social media, offer a flexible and convenient form of support to offer help at critical points, e.g., when the risk of breastfeeding cessation is high. Currently, there is little known about who accesses different forms of remote breastfeeding support and what factors impact overall satisfaction. As part of an evaluation of the UK National Breastfeeding Helpline (NBH) (which offers breastfeeding support via a helpline and online media), we aimed to (a) understand who accesses different forms of NBH support, and (b) identify key factors associated with overall satisfaction for helpline and online media support. Methods: All service users who contacted the NBH between November 2021 and March 2022 were invited to participate in the evaluation via an online survey. Survey questions explored the type and timing of support, reasons for the contact, attitudes towards the help and support received, impact of the support on breastfeeding experiences and demographic factors. Chi-squared and Mann–Whitney tests explored variations in who accessed the helpline or online media. Multiple linear regression models were fitted to explore the factors related to the service users' 'overall satisfaction'. The quantitive data were combined with qualitative comments into descriptive themes. Results: Overall, online media users were significantly more likely to be younger, White, multiparous, less educated and have English as a first language compared to those who contact the helpline. Similar factors that significantly influenced overall satisfaction for both support models were the service being easy to access, receiving helpful information that met expectations, resolving breastfeeding issues, and feeling reassured and more confident. Significant factors for the helpline were callers feeling understood and more knowledgeable about breastfeeding following the call, being able to put into practice the information provided, feeling encouraged to continue breastfeeding, feeling that the volunteer gave the support that was needed, and seeking out additional support. Conclusions: Online and helpline forms of breastfeeding support suit different demographics and call purposes. While optimal breastfeeding support needs to be accessible, flexible and instrumental, helpline users need real-time relational support to deal with more complex challenges. [ABSTRACT FROM AUTHOR]

Extracting biological interactions from published literature helps us understand complex biological systems, accelerate research, and support decision-making in drug or treatment development. Despite efforts to automate the extraction of biological relations using text mining tools and machine learning pipelines, manual curation continues to serve as the gold standard. However, the rapidly increasing volume of literature pertaining to biological relations poses challenges in its manual curation and refinement. These challenges are further compounded because only a small fraction of the published literature is relevant to biological relation extraction, and the embedded sentences of relevant sections have complex structures, which can lead to incorrect inference of relationships. To overcome these challenges, we propose GIX, an automated and robust Gene Interaction Extraction framework, based on pre-trained Large Language models fine-tuned through extensive evaluations on various gene/protein interaction corpora including LLL and RegulonDB. GIX identifies relevant publications with minimal keywords, optimises sentence selection to reduce computational overhead, simplifies sentence structure while preserving meaning, and provides a confidence factor indicating the reliability of extracted relations. GIX's Stage-2 relation extraction method performed well on benchmark protein/gene interaction datasets, assessed using 10-fold cross-validation, surpassing state-of-the-art approaches. We demonstrated that the proposed method, although fully automated, performs as well as manual relation extraction, with enhanced robustness. We also observed GIX's capability to augment existing datasets with new sentences, incorporating newly discovered biological terms and processes. Further, we demonstrated GIX's real-world applicability in inferring E. coli gene circuits. [ABSTRACT FROM AUTHOR]

Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy. Here, primary mouse cortical microglia were cultured with a GFP-functionalized PODS for 24 h. Cell counts, cell morphology and Iba1 expression were all unaltered in treated cultures, indicating a lack of acute toxicity or microglial activation. Microglia exhibited internalisation of the PODS, with both cytosolic and perinuclear localisation. No evidence of adverse effects on cellular morphology was observed. Overall, 20–40% of microglia exhibited uptake of the PODS, but extracellular/non-internalised PODS were routinely present after 24 h, suggesting that extracellular drug delivery may persist for at least 24 h. [ABSTRACT FROM AUTHOR]

Background: Mendelian randomisation (MR) is the use of genetic variants as instrumental variables. Mode-based estimators (MBE) are one of the most popular types of estimators used in univariable-MR studies and is often used as a sensitivity analysis for pleiotropy. However, because there are no plurality valid regression estimators, modal estimators for multivariable-MR have been under-explored. Methods: We use the residual framework for multivariable-MR to introduce two multivariable modal estimators: multivariable-MBE, which uses IVW to create residuals fed into a traditional plurality valid estimator, and an estimator which instead has the residuals fed into the contamination mixture method (CM), multivariable-CM. We then use Monte-Carlo simulations to explore the performance of these estimators when compared to existing ones and re-analyse the data used by Grant and Burgess (2021) looking at the causal effect of intelligence, education, and household income on Alzheimer's disease as an applied example. Results: In our simulation, we found that multivariable-MBE was generally too variable to be much use. Multivariable-CM produced more precise estimates on the other hand. Multivariable-CM performed better than MR-Egger in almost all settings, and Weighted Median under balanced pleiotropy. However, it underperformed Weighted Median when there was a moderate amount of directional pleiotropy. Our re-analysis supported the conclusion of Grant and Burgess (2021), that intelligence had a protective effect on Alzheimer's disease, while education, and household income do not have a causal effect. Conclusions: Here we introduced two, non-regression-based, plurality valid estimators for multivariable MR. Of these, "multivariable-CM" which uses IVW to create residuals fed into a contamination-mixture model, performed the best. This estimator uses a plurality of variants valid assumption, and appears to provide precise and unbiased estimates in the presence of balanced pleiotropy and small amounts of directional pleiotropy. [ABSTRACT FROM AUTHOR]

This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such as doxorubicin and paclitaxel. This manuscript details the design and benefits of various LNP systems, including solid lipid–polymer hybrids, which offer controlled release and enhanced drug encapsulation. Despite achievements in reducing tumor size and enhancing survival, challenges such as manufacturing complexity, biocompatibility, and variable clinical outcomes persist. Future directions are aimed at refining targeting capabilities, expanding combinatorial therapies, and integrating advanced manufacturing techniques to tailor treatments to individual patient profiles, thus promising to transform lung cancer therapy through interdisciplinary collaboration and regulatory innovation. [ABSTRACT FROM AUTHOR]

The United Nations Subcommittee on the Prevention of Torture visits signatory nations to the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment (OPCAT). Its role is to monitor and support signatory nations in implementing and complying with the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment (CAT). In October 2022, the United Nations Subcommittee on the Prevention of Torture visited Australia but was barred from visiting mental health wards in Queensland and all detention facilities in New South Wales leading to the termination of its visit. This breach of Australia's obligations under the OPCAT presents a significant setback for the rights of people with mental illness and other involuntarily detained populations. This piece sets out to demonstrate the relevance of OPCAT to the mental health system in Australia. Individuals who are detained for compulsory treatment in locked facilities such as acute psychiatric inpatient wards and forensic mental health facilities are deprived of their liberty, often out of public view. Thus, it highlights the ethical and professional obligations of all mental health professionals, especially psychiatrists, to safeguard the human rights of individuals being detained in mental health facilities as enshrined in Australia's international legal obligations under the OPCAT. Adhering to these obligations diminishes the risk of future human rights violations of people with mental illness. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support (MCS) devices can bridge the gap to transplant whilst awaiting a viable donor heart. The Realheart Total Artificial Heart is a novel positive-displacement MCS that generates pulsatile flow via bileaflet mechanical valves. This study developed a combined computational fluid dynamics and fluid-structure interaction (FSI) methodology for simulating positive displacement bileaflet valves. Overset meshing discretised the fluid domain, and a blended weak-strong coupling FSI algorithm was combined with variable time-stepping. Four operating conditions of relevant stroke lengths and rates were assessed. The results demonstrated this modelling strategy is stable and efficient for modelling positive-displacement artificial hearts. [ABSTRACT FROM AUTHOR]

Background In vitro–in vivo discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P <.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L). Conclusions Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome. [ABSTRACT FROM AUTHOR]

There is a growing evidence base that identifying positive experiences in providing care can have a beneficial influence on carer wellbeing. However, there is a need to better understand what carers identify as the positive aspects of care-giving. The aim of this study is to explore the satisfying aspects of providing care to people with dementia. This study utilised Time 1 data from 1,277 carers of people in the mild-to-moderate stages of dementia taking part in the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort study. Responses from 900 carers who answered the open-ended question 'What is your greatest satisfaction in caring for your relative/friend?' were analysed using thematic analysis. From the responses, 839 carers detailed satisfactions. Eight themes were identified, pertaining to three groups of beneficiaries: carers, people with dementia and the dyad. Perceived benefits for carers included identifying aspects of personal growth, seeing glimpses of the person, feeling they were making a difference and doing their duty. For the person with dementia, these included retaining independence, receiving good quality care and being happy. Dyadic benefits concerned the continuation of the relationship between carer and person with dementia. The findings highlight the need to take a dyadic approach when conceptualising positive experiences in providing care. Further research is needed to understand the role these positive experiences play and to develop interventions. Professionals working with carers should identify and validate these experiences. [ABSTRACT FROM AUTHOR]

Research Summary: This paper describes Rainier Beach: A Beautiful Safe Place for Youth (ABSPY), a community‐led, place‐based, data‐driven initiative to improve community safety and reduce crime involving young people at hot spots in Seattle, Washington. The ABSPY model puts crime prevention into the hands of the community, compared to traditional problem‐solving approaches that may involve community stakeholders but are led by the police. We evaluated the initiative using a quasi‐experimental research design comparing the five hot spots in the Rainier Beach neighborhood, where ABSPY was implemented, to five similarly situated hot spots elsewhere in the city. We used 9 years of police calls for service and offense reports, from 2011 to 2019, to assess ABSPY's effects on crime and a five‐wave community survey conducted pre‐ and 4 years post‐implementation to examine community perceptions. Although there were no significant effects on calls for service or crime, ABSPY significantly improved community members' perceptions of serious crime and the police in the short and medium term. Policy Implications: Our results show positive changes in community perceptions that offer a foundation for relationship and capacity building in problem‐solving efforts. Although ABSPY is not associated with reductions in crime, our results suggest that even communities with entrenched crime problems can leverage this capacity to reduce crime in the longer term. Community coalitions also offer some benefits relative to police‐led efforts, such as shared culture and values; stability; and consistency. However, community coalitions must build capacity for action as well as community engagement, and consider if and how the police should be involved, ensuring that the specific expertise of each coalition member is leveraged. Furthermore, our study highlights the importance of identifying measures of crime that are not affected by increased trust and collaboration between the police and the community. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether leukocytospermia (defined as the presence of ≥ 1 × 106 white blood cells/mL) affects clinical and embryologic outcomes in in vitro fertilization (IVF) cycles with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A). Methods: This was a retrospective cohort study including 5425 cycles between January 2012 to December 2021 at a single large university-affiliated fertility clinic. The primary outcome was live birth rate (LBR). Results: The prevalence of leukocytospermia was 33.9% (n = 1843). Baseline characteristics including female age, BMI, AMH, Day 3 FSH, and male partner's age were similar in cycles with and without leukocytospermia. The LBR after the first euploid embryo transfer was similar in those with and without leukocytospermia (62.3% vs. 63% p = 0.625). Secondary outcomes including clinical pregnancy rate (CPR), sustained implantation rate (SIR), fertilization (2PN) rate, blastulation rate, and aneuploidy rate were also evaluated. The CPR (73.3% vs 74.9%, p = 0.213) and SIR (64.6% vs. 66%, p = 0.305) were similar in both groups. The 2PN rate was also similar in both groups (85.7% vs. 85.8%, p = 0.791), as was the blastulation rate per 2PN (56.7% vs. 57.5%, p = 0.116). The aneuploidy rate was not significantly different between groups (25.7% vs 24.4%, p = 0.053). A generalized estimation equation with logistic regression demonstrated that the presence leukocytospermia did not influence the LBR (adjusted OR 0.878; 95% CI, 0.680–1.138). Conclusion: Leukocytospermia diagnosed just prior to an IVF cycle with PGT-A does not negatively impact clinical or embryologic outcomes. [ABSTRACT FROM AUTHOR]

Objective: Most states prohibit sales of alcohol to customers who are apparently intoxicated, and many require training in responsible beverage service (RBS), with the aim of reducing driving while intoxicated (DWI) and other harms. Sales to apparently intoxicated patrons were assessed in onsite alcohol sales establishments and compared across three states. Method: A sample of 180 licensed onsite alcohol establishments was selected in California (n = 60), New Mexico (n = 60), and Washington State (n = 60). States had different RBS training histories, content, and procedures. Research confederates, trained to feign cues of intoxication, visited each establishment twice. The pseudo-intoxicated patron (PP) ordered an alcoholic beverage while displaying intoxication cues. Sale of alcohol was the primary outcome. Results: At 179 establishments assessed, PPs were served alcohol during 56.5% of 356 visits (35.6% of establishments served and 22.6% did not serve at both visits). Alcohol sales were less frequent in New Mexico (47.9% of visits; odds ratio [OR] = 0.374, p = .008) and Washington State (49.6%; OR = 0.387, p = .012) than in California (72.0%). Servers less consistently refused service at both visits (6.8%) in California than New Mexico (33.9%) or Washington (27.1%), χ²(4, n = 177) = 16.72, p = .002. Alcohol sales were higher when intoxication cues were less obvious (p < .001). Conclusions: Overservice of alcohol to apparently intoxicated customers was frequent and likely elevated risk of DWI and other harms. The lower sales in New Mexico and Washington than California may show that a policy approach prohibiting sales to intoxicated customers combined with well-established RBS training can reduce overservice. Further efforts are needed to reduce overservice. [ABSTRACT FROM AUTHOR]

This document provides information on various compounds, specifically N-formyl derivatives, and their spectroscopic data. The compounds mentioned include a wide range of derivatives with different functional groups. The compounds were purified and their spectroscopic data were compared to existing literature, confirming their identities. The document also acknowledges the scholarship awarded to one of the researchers. [Extracted from the article]

The article discusses the launch of the funding opportunities by the National Institute on Aging (NIA) targeting clinician-scientists focused on aging research from a diverse array of specialties and disciplines. Topics include the Grants for Early Medical and Surgical Specialists' Transition to Aging Research (GEMSSTAR) initiative of the NIA, the expansion made by the NIA on its commitment to support a wider range of clinician-scientists, and the infrastructure grant launched by the NIA.

Background: The risk of incident dementia after surgery in older adults is unclear. The study objective was to examine the rate of incident dementia among older adults after elective surgery compared with a matched nonsurgical control group. Methods: We conducted a population‐based, propensity‐matched retrospective cohort study using data from linked administrative databases in Ontario, Canada. All community‐dwelling individuals aged 66 years and older who underwent one of five major elective surgeries between April 1, 2007 and March 31, 2011 were included. Each surgical patient was matched 1:1 on surgical specialty of the surgeon at consultation, age, sex, fiscal year of entry, and propensity score with a patient who attended an outpatient visit with a surgeon of the same surgical specialty but did not undergo surgery. Patients were followed for up to 5 years after cohort entry for the occurrence of a new dementia diagnosis, defined from administrative data. Cause‐specific hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between surgery and the hazard of incident dementia. Subgroup and sensitivity analyses were performed. Results: A total of 27,878 individuals (13,939 matched pairs) were included in the analysis. A total of 640 (4.6%) individuals in the surgical group and 965 (6.9%) individuals in the control group developed dementia over the 5‐year follow‐up period. Individuals who underwent surgery had a reduced rate of incident dementia compared with their matched nonsurgical controls (HR 0.88; 95% CI 0.80–0.97; p = 0.01). This association was persistent in most subgroups and after sensitivity analyses. Conclusions: Elective surgery did not increase the rate of incident dementia when compared with matched nonsurgical controls. This could be an important consideration for patients and surgeons when elective surgery is considered. See related editorial by Tammy Hshieh and article by Tang et al. in this issue. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5–99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93–1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58–1.21, P  = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5–99.6%). LIMITATIONS, REASONS FOR CAUTION Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(s) None. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]