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Abstract M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT.

Introduction

ABSTRACT As one of the most threatened mammalian taxa, lemurs of Madagascar are facing unprecedented anthropogenic pressures. To address conservation imperatives such as this, researchers have increasingly relied on conservation genomics to identify populations of particular concern. However, many of these genomic approaches necessitate high‐quality genomes. While the advent of next‐generation sequencing technologies and the resulting reduction in associated costs have led to the proliferation of genomic data and high‐quality reference genomes, global discrepancies in genomic sequencing capabilities often result in biological samples from biodiverse host countries being exported to facilities in the Global North, creating inequalities in access and training within genomic research. Here, we present the first published reference genome for the endangered red‐fronted brown lemur (Eulemur rufifrons) from sequencing efforts conducted entirely within the host country using portable Oxford Nanopore sequencing. Using an archived E. rufifrons specimen, we conducted long‐read, nanopore sequencing at the Centre ValBio Research Station near Ranomafana National Park, in rural Madagascar, generating over 750 Gb of sequencing data from 10 MinION flow cells. Exclusively using this long‐read data, we assembled 2.157 gigabase, 2980‐contig nuclear assembly with an N50 of 101.6 Mb and a 17,108 bp mitogenome. The nuclear assembly had 30× average coverage and was comparable in completeness to other primate reference genomes, with a 96.1% BUSCO completeness score for primate‐specific genes. As the first published reference genome for E. rufifrons and the only annotated genome available for the speciose Eulemur genus, this resource will prove vital for conservation genomic studies while our efforts exhibit the potential of this protocol to address research inequalities and build genomic capacity.

Abstract The rational and controlled synthesis of metallo‐organic cages using polyaromatic ligands is well established in the literature. There is a strong interest to advance this field towards the use of chiral ligands capable of yielding cages in a stereoselective manner. Herein, we demonstrate that the classical approach for designing metallo‐organic cages can be translated to polyproline peptides, a biocompatible class of chiral ligands. We have successfully designed a series of polyprolines, which mimic the topology of ditopic polyaromatic ligands, to achieve the stereoselective synthesis of a novel Pd lantern cage. This cage exhibits excellent stability in water and demonstrates the stabilization of a highly reactive species in solution. This work will pave the way towards the stereospecific synthesis of more complex, functionalized peptide‐based metallo‐cages.

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections. Methods: Data were drawn from a surveillance study of households with children (N = 1913) recruited from 12 U.S. cities during the initial year of the pandemic and followed for 28 weeks (data collection: 1-May-2020 through 22-Feb-2021). Caregivers rated how much they worried about family members getting COVID-19 and subsequently reported household levels of outside-the-home social activities that could increase risk for SARS-CoV-2 transmission at 14 follow-ups. Caregivers collected household nasal swabs on a fortnightly basis and peripheral blood samples at study conclusion to monitor for SARS-CoV-2 infections by polymerase chain reaction and serology. Primary analyses used generalized linear and generalized mixed-effects modelling. Results: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with lower COVID-19 worry had higher odds of (a) reporting discretionary outside-the-home social interaction and (b) SARS-CoV-2 infection. Conclusions: This was, to our knowledge, the first study showing that caregiver COVID-19 illness worry was predictive of both COVID-19 mitigation compliance and laboratory-determined household infection. Findings should inform studies weighing the adaptive value of worrying about infectious disease outbreaks against established detrimental health effects.

Objective Non-alcoholic fatty liver disease (NAFLD) is estimated to affect a third of Australian adults, and its prevalence is predicted to rise, increasing the burden on the healthcare system. The LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD) trialled a community-based fibrosis assessment service using FibroScan to reduce the time to diagnosis of high-risk NAFLD and improve patient outcomes.Methods We conducted a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD diagnosis and assessment. Participants had suspected NAFLD and were referred to a hepatology clinic in one of three major hospitals in South-East Queensland. Eligible consenting participants were randomised to receive usual care or the intervention (LOCATE). Participants in the intervention arm received a FibroScan outside of the hospital setting, with results provided to their primary care provider and the referring hepatologist. All participants were followed up 12 months after randomisation to measure their clinical and patient-reported outcomes.Results 97 participants were recruited from October 2020 to December 2022. Of the 50 participants randomised to the intervention arm, one failed to attend their appointment, and of the 48 (98%) who had a FibroScan 13 (27%) had a liver stiffness measurement of 8.0 kPa or greater. The HR for the time to diagnosis of high risk was 1.28 (95% CI 0.59 to 2.79), indicating a faster average time to diagnosis with the intervention, but failing to conclusively demonstrate a faster time. The intervention did greatly reduce the time to FibroScan by almost 1 year (median difference 0.92 years, 95% CI 0.56 to 1.45). Other clinical outcomes showed minimal changes.Conclusion The LOCATE model shows potential for impact, particularly in reducing waiting times for patients at high risk of developing severe liver disease due to NAFLD. A larger sample and longer follow-ups are needed to measure additional clinical outcomes.Trial registration number ACTRN12620000158965.

ABSTRACT Aims To examine the predictability of categorical and quantitative study variables on acute stroke knowledge amongst study participants. Design Non‐experimental, descriptive correlational. Methods A convenience sample of registered nurses caring for adult, hospitalized patients recruited from the urban Southeast. A three‐part survey was emailed to the nurses: demographics, stroke education and experience, and the Acute Stroke Management Questionnaire. Results Intensive Care Unit and Emergency Department nurses had the highest level of stroke knowledge. Nurses reporting three or more post‐licensure education modalities had higher stroke knowledge scores than those reporting two or less. Practice setting, self‐perception of stroke knowledge, self‐identified knowledge of acute stroke management and three items related to code stroke were significantly correlated with stroke knowledge. Conclusion Various methods of training and reinforcement of learning using varying teaching styles are effective in increasing nurses' stroke knowledge. Further stroke education is needed for nurses across the acute care setting. Implications Future studies should explore lived experiences of nurses to gain understanding of nonquantifiable factors that nurses feel have strengthened their stroke knowledge. Impact What Problem Did the Study Address? ○Addressing the gap in the knowledge of predictors of nurse stroke knowledge. Main Findings? Practice setting, post‐licensure stroke education, code stroke familiarity, confidence and understanding were all predictive of the overall stroke knowledge. Whom Will the Research Have an Impact? Nurses, nurse educators, patients experiencing and at risk for stroke. Reporting Method The STROBE checklist was used to strengthen the reporting of the results. Patient or Public Contribution Nurses voluntarily participated in this study by completing the online questionnaire. What Does This Paper Contribute to the Wider Global Clinical Community? Provides predictors of stroke knowledge for nurse leaders to have a better understanding of nurses' educational needs. Provides evidence of a quick, effective measure of nurses' stroke knowledge.

Mentorship is critical to fostering professional growth and career development in academia. However, academic mentorship is often an informal activity that is overlooked and under researched. There is much ambiguity and uncertainty surrounding mentorship roles and strategies in academia. This paper provides recommendations and strategies to reframe and advance academic mentorship to support new and early career faculty.

Objective To evaluate modified versions of the Belimumab International Study in Lupus Nephritis (BLISS-LN) belimumab study primary efficacy renal response (mPERR) and complete renal response (mCRR) criteria (excluding mandatory corticosteroid tapering) as predictors of real-world, long-term renal outcomes among patients with lupus nephritis (LN).Methods This retrospective, observational study (GSK Study 212866) used deidentified data between 1970 and 2015 from the University of Toronto Lupus Cohort from adults diagnosed with systemic lupus erythematosus and biopsy-proven Class III±V, IV±V or V LN. At 24 months postbiopsy, patients were retrospectively indexed as responders/non-responders based on mPERR (estimated glomerular filtration rate (eGFR) ≤20% below biopsy value/≥60 mL/min/1.73 m2 and urine protein:creatinine ratio (uPCR) ≤0.7 g/day) or mCRR (eGFR ≤10% below biopsy value/≥90 mL/min/1.73 m2 and uPCR ≤0.5 g/day) criteria. The association between index mPERR (primary outcome) or mCRR (secondary outcome) status and long-term (up to 25 years, until censoring or death) renal survival (no progression to end-stage kidney disease (eGFR

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1-6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus. These data included 206 biopsies in Barrett's oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case-control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett's-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.

Understanding mechanistic details of the nickel-catalyzed coupling reactions of Csp3 alcohol derivatives is key to developing selective reactions of this widely prevalent functional group. In this manuscript, we utilize a combination of experimental data and DFT studies to define the key intermediates, stereochemical outcome, and competing pathways of a nickel-catalyzed cross-electrophile coupling reaction of 1,3-dimesylates. Stereospecific formation of a 1,3-diiodide intermediate is achieved in situ by the Grignard reagent. The overall stereoablative stereochemical outcome is due to a nickel-catalyzed halogen atom abstraction with a radical rebound that is slower than epimerization of the alkyl radical. Finally, lifetimes of this alkyl radical intermediate are compared to radical clocks to enhance the understanding of the lifetime of the secondary alkyl radical.

ObjectiveTo compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality.Summary of background dataPHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF.MethodsAdults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades.ResultsAmong 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality.ConclusionsIn this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Introdução: O uso desnecessário e inadequado de antimicrobianos de amplo espectro em hospitais contribuem para a seleção e disseminação de microrganismos resistentes, além de trazer risco de eventos adversos aos pacientes e riscos financeiros para as instituições de saúde. O Time Out é uma intervenção que consiste na avaliação e revisão periódica do tratamento antimicrobiano conforme a evolução clínica do paciente e resultados laboratoriais. Informações como indicação, dose, via de administração, duração da terapia e possibilidade de descalonamento são avaliadas para adequar a terapia e evitar o uso desnecessário de antimicrobianos. A ceftazidima-avibactam é um antimicrobiano de amplo espectro e alto custo que requer atenção especial dos programas de gerenciamento devido à importância de preservar sua eficácia frente ao crescente desafio da resistência bacteriana. Objetivo: Avaliar o impacto do Time Out na utilização de ceftazidima-avibactam em um hospital particular e filantrópico de alta complexidade. Método: Estudo intervencional prospectivo incluindo pacientes adultos internados em uso de ceftazidima-avibactam por mais de 72h no período de Junho/2023 a Março/2024. O Time Out foi realizado por farmacêuticos clínicos e as intervenções farmacêuticas foram registradas e analisadas. O consumo de ceftazidima-avibactam foi medido em Dose Diária Definida (DDD) e Dias de Terapia (DOT). Resultados: Foram realizadas 191 avaliações para um total de 105 pacientes no período referido. Um total de 61 intervenções farmacêuticas de relevância clínica foram registradas com a realização do Time Out. As principais intervenções foram relacionadas a ajustes posológicos (56%, em sua maioria baseada na função renal) e indicação terapêutica (31%, majoritariamente devido ao término do tempo de tratamento). Observou-se uma tendência de redução do consumo (DDD e DOT) no período, sendo mais acentuada de Dezembro/2023 a Março/2024. Conclusão: A realização do Time Out a partir de 72h do início da terapia antimicrobiana se mostrou uma ferramenta eficaz na identificação de possíveis intervenções farmacêuticas, principalmente relacionadas ao ajuste posológico e tempo de tratamento. Essas intervenções contribuíram para a otimização terapêutica e redução do consumo desnecessário de ceftazidima-avibactam. O Time Out de antimicrobianos pode ser implementado na prática clínica visando uma utilização mais racional e eficaz dos recursos terapêuticos, sendo uma estratégia eficiente de gestão de antimicrobianos em ambiente hospitalar.

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

BackgroundLysosomal storage diseases (LSDs) are inherited metabolic disorders that may lead to severe multi-organ disease. Current ERTs are limited by anti-drug antibodies, the blood-brain barrier, and early disease onset and progression before ERT is started. We have opened a phase I clinical trial of enzyme replacement therapy (ERT) for fetuses with LSDs (NCT04532047). We evaluated the attitudes of parents and patients with LSDs towards fetal clinical trials and therapies.MethodsA multidisciplinary team designed a survey which was distributed by five international patient advocacy groups. We collected patients' demographic, diagnostic, and treatment information. Associations between respondent characteristics and attitudes towards fetal therapies/trials were analyzed using multivariate ordinal logistic regression.ResultsThe survey was completed by 181 adults from 19 countries. The majority of respondents were mothers from the United States. The most common diseases were MPS1 (26%), MPS3 (19%), and infantile-onset Pompe (14%). Most patients (88%) were diagnosed after birth, at a median of 21 months. Altogether, 65% of participating patients and children of participants had received ERT, 27% a stem cell transplant, and 4% gene therapy. We found that half (49%) of respondents were unlikely to terminate a future affected pregnancy, 55% would enroll in a phase I clinical trial for fetal ERT, and 46% would enroll in a fetal gene therapy trial. Respondents who received postnatal ERT were significantly more likely enroll in a trial for fetal ERT or gene therapy (ERT OR 4.48, 95% CI 2.13-9.44, p

Abstract The loss and degradation of forests and other ecosystems worldwide threaten both global biodiversity and the livelihoods of people who use natural resources. Understanding how natural resource use impacts landscape provisioning services for both people and wildlife is thus critical for designing comprehensive resource management strategies. We used data from community focus groups, botanical plots and an inventory of plant species consumed by the Critically Endangered red‐ruffed lemur (Varecia rubra) to assess the availability of key provisioning services for people and endemic wildlife on the Masoala Peninsula, a rainforest transformation landscape, in northeastern Madagascar (Masoala National Park and 13 surrounding communities). We constructed Poisson regression mixed models to evaluate the impact of community factors (i.e. community population size, plot distance to community) and changes over time on the count and species richness of timber trees, medicinal plants and red‐ruffed lemur food trees within botanical plots. Over three‐quarters of all plant species could be used for at least one purpose by local communities (n = 238 species). Of the 59 V. rubra food tree species, only 15% had no reported human use. Timber and ruffed lemur food tree availability declined both with community population size and time and were predicted to be lower outside of Masoala National Park. In contrast, medicinal plant availability was not strongly predicted by any tested factors. Provisioning service availability also differed strongly across sites, suggesting that additional, untested proxies of human pressure likely also have an effect. Our results highlight the importance of evaluating natural resource availability from a community‐based perspective and by resource purpose to inform forest landscape restoration efforts that can support both people and wildlife. Read the free Plain Language Summary for this article on the Journal blog.

Coffee quality, which ultimately is reflected in the beverage aroma, relies on several aspects requiring multiple approaches to check it, which can be expensive and/or time-consuming. Therefore, this study aimed to develop and calibrate an electronic nose (e-nose) coupled with chemometrics to approach coffee-related quality tasks. Twelve different metal oxide sensors were employed in the e-nose construction. The tasks were (i) the separation of Coffea arabica and Coffea canephora species, (ii) the distinction between roasting profiles (light, medium, and dark), and (iii) the separation of expired and non-expired coffees. Exploratory analysis with principal component analysis (PCA) pointed to a fair grouping of the tested samples according to their specification, indicating the potential of the volatiles in grouping the samples. Moreover, a supervised classification employing soft independent modeling of class analogies (SIMCA), partial least squares discriminant analysis (PLS-DA), and least squares support vector machine (LS-SVM) led to great results with accuracy above 90% for every task. The performance of each model varies with the specific task, except for the LS-SVM models, which presented a perfect classification for all tasks. Therefore, combining the e-nose with distinct classification models could be used for multiple-purpose classification tasks for producers as a low-cost, rapid, and effective alternative for quality assurance.

Limited contemporary data has compared similarities and differences between total laparoscopic (LDP), hand-assisted (HALDP), and open distal pancreatectomy (ODP). This study aimed to examine similarities and differences in outcomes between these three approaches in a contemporary cohort. Methods: Patients undergoing elective LDP, HALDP, and ODP in the NSQIP dataset (2014−2019) were included. Descriptive statistics and multivariate regression analyses were employed to compare postoperative outcomes. Results: Among 5636 patients, 33.9% underwent LDP, 13.1% HALDP, and 52.9% ODP. Compared with the LDP approach, surgical site infections were more frequent in HALDP and ODP approaches (1.2% vs. 2.6% vs. 2.8%, respectively, p < 0.01). After adjustment, the LDP approach was associated with a significantly lower likelihood of surgical site infection (OR 0.25, p = 0.03) when compared to ODP. There was no difference in the likelihood of surgical site infection when HALDP was compared to ODP (OR 0.59, p = 0.40). Unadjusted operative times were similar between approaches (LDP = 192 min, HALDP = 193 min, ODP = 191 min, p = 0.59). After adjustment, the LDP approach had a longer operative time (+10.3 min, p = 0.04) compared to ODP. There was no difference in the adjusted operative time between HALDP and ODP approaches (+5.4 min, p = 0.80). Conclusions: Compared to ODP, LDP was associated with improved surgical site infection rates and slightly longer operative times. There was no difference in surgical site infection rates between ODP and HALDP. Surgeon comfort and experience should decide the operative approach, but it is important to discuss the differences between these approaches with patients.

BackgroundFalls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk.MethodsWe assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL.ResultsFor recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months.ConclusionsAcross a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects.Clinicaltrialsgov identifier: NCT02475850.

The purpose of this investigation was to explore through a historical case study the ways in which one principal mentored and built capacity with a school-based cohort of teachers who became school leaders themselves in a variety of capacities. Findings reveal a generative female leader who embraced strong philosophical and theoretical foundations enacted in an enriching, innovative culture. This case study illustrates the nested activity of leadership in the development of a learning organization focused on strong relationships, continuous adult learning, and practical leading capacities. This nested activity contributed to leadership dispersion, strong community identity, and personal transformative experiences for teachers who chose to become leaders as well. Findings suggest ways in which principals in contemporary schools can mentor and develop teachers to become teacher leaders and learning-centered administrators.

Infants growing up in low- and middle-income countries are at increased risk of suffering adverse childhood experiences, including exposure to environmental pollution and lack of cognitive stimulation. In this study, we aimed to examine the levels of metals in the human milk of women living in São Paulo City, Brazil, and determine the effects on infants’ neurodevelopment. For such, a total of 185 human milk samples were analyzed for arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd) using inductively coupled plasma mass spectrometry (ICP-MS). We applied the Bayley scales of infant and toddler development Third Edition (Bayley-III) to assess developmental milestones. In our analysis, we found a mean (standard deviation) concentration of As in human milk equal to 2.76 (4.09) μg L−1, followed by Pb 2.09 (5.36) and Hg 1.96 (6.68). Cd was not detected. We observed that infants exposed to Pb presented language trajectories lower than non-exposed infants (β = −0.413; 95% CI -0.653, −0.173) after adjustment for infant age, maternal education, socioeconomic status, infant sex, and sample weights. Our results report As, Pb, and Hg contamination in human milk, and that infant exposure to Pb decreased infants’ language development. These results evidence maternal-child environmental exposure and its detrimental impact on infants’ health.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Abstract Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage‐induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4‐fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and growth of a charismatic mega moth (Anthereae polyphemus). This work suggests that changes to the phytochemical landscape of forests, mediated by invasive outbreak insects, are likely to negatively impact native insects, with potential repercussions for community diversity and ecosystem function across expansive scales.

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is associated with an increased risk of extrahepatic morbidity. We compared the incidence of cancers in adults admitted to Queensland hospitals with MASLD with that for the Queensland population and examined the association between cirrhosis and type 2 diabetes and the development of extrahepatic cancers. Methods In this retrospective study, we identified all cancers (Queensland Cancer Registry) after the first hospitalization with MASLD during Jul‐2007 to Dec‐2019, estimated age‐standardized incidence (ASI) of cancers, and compared that with the ASI in the Queensland population (incidence rate ratios [IRR]). Among the MASLD cohort, we examined the association between diabetes and cancer risk (Cox regression). Median follow‐up was 3.8 years (54 204 person‐years). Results Totally 1104 new cancers were diagnosed in 1018 patients (8.9% of 9771 non‐cirrhotic and 1712 adults with cirrhosis). The ASI (all cancers) of 1668.2 per 100 000 person‐years in men (95% CI 1523.7–1827.4) and 1284.0 per 100 000 person‐years in women (95% CI 1169.6–1408.2) was 2‐fold higher than that of the Queensland population (IRR = 1.94, 95% CI 1.75–2.16 and IRR = 1.99, 95% CI 1.78–2.22, respectively). Incidence of stomach cancer, unknown primary, and pancreas was 3‐ to 5‐fold higher compared to the general population (all P

Background Tracking the spread of antibiotic resistant bacteria is critical to reduce global morbidity and mortality associated with human and animal infections. There is a need to understand the role that wild animals in maintenance and transfer of antibiotic resistance genes (ARGs). Methods This study used metagenomics to identify and compare the abundance of bacterial species and ARGs detected in the gut microbiomes from sympatric humans and wild mouse lemurs in a forest-dominated, roadless region of Madagascar near Ranomafana National Park. We examined the contribution of human geographic location toward differences in ARG abundance and compared the genomic similarity of ARGs between host source microbiomes. Results Alpha and beta diversity of species and ARGs between host sources were distinct but maintained a similar number of detectable ARG alleles. Humans were differentially more abundant for four distinct tetracycline resistance-associated genes compared to lemurs. There was no significant difference in human ARG diversity from different locations. Human and lemur microbiomes shared 14 distinct ARGs with highly conserved in nucleotide identity. Synteny of ARG-associated assemblies revealed a distinct multidrug-resistant gene cassette carrying dfrA1 and aadA1 present in human and lemur microbiomes without evidence of geographic overlap, suggesting that these resistance genes could be widespread in this ecosystem. Further investigation into intermediary processes that maintain drug-resistant bacteria in wildlife settings is needed.

IntroductionCeftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum β-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible.MethodsAntimicrobial susceptibility was determined through agar dilution and broth microdilution, while blaPER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of blaPER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. ResultsTwenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried blaPER. One isolate carried blaPER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their blaPER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of blaPER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the in vitro evolved isolate. DiscussionPER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other β-lactams.

Introduction: Ambulatory mobility aids are several devices the elderly may use in order to improve their walking pattern, balance, or safety while mobilizing independently. Objectives: To assess the effect of ambulatory mobility aid devices on cardiovascular parameters, walking speed, perceived exertion, and balance of older adult men. Methods: A sample of 156 old men was studied. Data were obtained through measurement of the participants’ walking speed (distance covered/second), cardiovascular parameters (blood pressure), perceived exertion (difficulty or ease in breathing), and balance (ease in standing) after walking with and without the selected walking aid devices. Analysis was done to compare the effect of the walking aid devices on the selected dependent variables. Results: Results showed ambulation with mobility aid devices resulted in increase in the heart rate and blood pressure with the greatest increase observed when walking with Zimmer frame. Ambulation with mobility aid devices resulted in decrease of the walking speed of the participants when compared to ambulation without devices. Perceived exertion of participants after using Zimmer frame and walking cane was within 4.06 ± 1.35 and 3.98 ± 1.26, respectively, as opposed to 3.08 ± 0.73 after ambulation without aid. Use of Zimmer frame provided enough balance for participants. Conclusion: Ambulatory mobility devices caused difference in cardiovascular parameters when compared to ambulation at rest and without aid. It was recommended that selection of ambulatory mobility aid devices should depend on objective mobility assessments and periodical re-evaluation to ensure that it suits a person’s functional requirements and physical capabilities.