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IntroductionLymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.MethodsWe retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.ResultsFrom June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin’s lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2–4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2–4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).DiscussionAs the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

Background Physician underprescribing and patient nonadherence are major barriers to the benefits of guideline‐directed medical therapy. An important contributor to both underprescribing and patient nonadherence is concern about medication‐related side effects. Yet, there are few to no data on approaches used by physicians to: (1) elicit medication‐related side effects, (2) attribute these side effects to specific medications, and (3) take appropriate action. Methods and Results The authors conducted semistructured interviews with physicians to identify facilitators and barriers to each critical step of heart failure medication management: elicitation of side effects, attribution of side effects to a medication, and action in response to attributed side effects. Interviews were transcribed and coded using directed content analysis. For elicitation of potential side effects, limited patient communication and family discordance in reporting were key barriers, whereas guiding questions, measurement, and open channels of communication were key facilitators. For attribution of side effects, confounding from other medications, limited time for clinical encounters, and nonspecific symptoms were key barriers, whereas time‐limited medication discontinuation trials and medication rechallenges were key facilitators. For taking action, challenges with weighing risks and benefits and physician fear about causing harm or interfering with other clinicians were barriers, whereas patient‐physician communication and the results of a medication discontinuation trials and medication rechallenge were facilitators. Conclusions This study generated key facilitators and barriers to 3 key aspects of heart failure medication management related to side effects that should drive future work to improve heart failure medication management.

BackgroundParasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome.MethodsA matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community.ResultsIn simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia.ConclusionThe findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.

Key Clinical Message This case demonstrated the rare “shark fin” ECG pattern, an ST‐segment elevation typically seen in acute myocardial infarction. We reported a case of takotsubo cardiomyopathy secondary to influenza A infection with multiple organ failure, showing the shark fin sign and resulting in in‐patient mortality and various complication.

Background and purpose: It is still debatable which is the least invasive approach to the hip joint in arthroplasty for a femoral neck fracture (FNF). We compared the traditional direct lateral approach (DLA) with the direct anterior approach (DAA) regarding creatine kinase (CK), C-reactive protein (CRP), and hemoglobin (Hb). Methods: In a randomized controlled trial, 130 elderly patients with dislocated FNFs treated with total hip arthroplasty (THA) were included. CK, CRP, and Hb were measured preoperatively and on postoperative days 1 to 4 and were compared between the DAA and DLA groups using repeated measures mixed-effect models. Results: The CK level was significantly higher on the 1st postoperative day in the DLA group, 597 U/L (95% confidence interval [CI] 529–666) vs 461 U/L (CI 389–532), estimated mean difference (MD) 136 U/L (CI 38–235). The CRP levels were significantly higher on postoperative days 3 and 4 in the DLA group, 207 mg/L (CI 189–226) vs 161 mg/L (CI 143–180), estimated MD 46 mg/L (CI 19–72) and 162 mg/L (CI 144–181) vs 121 (CI 102–140), estimated MD 41 mg/L (CI 15–68). Blood loss, expressed as difference in Hb, did not differ between the groups. Conclusion: In an elderly population with FNFs, we found that the DAA, compared with the DLA, results in less CK and CRP increase, but no change in Hb.

RESUMO: O texto examina a dinâmica político-ideológica e o conteúdo da hegemonia empresarial na política para o ensino médio em Pernambuco. A análise se debruça sobre os intelectuais organizadores da política, os aparelhos privados de hegemonia, as orientações político-ideológicas e o comportamento dos setores e representantes dos subalternos frente ao Procentro e, posteriormente, ao Programa de Educação Integral. Para tanto, foi realizada a análise de documentos oficiais e de instituições privadas à luz de categorias gramscianas, com destaque para revolução passiva e transformismo. Conclui-se que a hegemonia empresarial na política em tela expressa um movimento de modernização-restauradora da racionalidade gerencial, revisando aspectos ideológicos secundários à hegemonia empresarial para incorporar, residualmente, demandas dos subalternos. Isso resulta num projeto, no plano da aparência, mais “social” e “inclusivo” de gerencialismo que, por sua vez, ocasiona fenômenos de transformismos como expressões de apassivamento das oposições ao modelo gerencial. Destaca-se, também, que o movimento de modernização-restauradora analisada em Pernambuco é parte de um bloco histórico dirigido por setores progressivos da política e da sociedade civil que caracteriza uma revolução passiva à brasileira e seu social-liberalismo (CASTELO, 2011).

BackgroundDigital Mental Health (DMH) tools are an effective, readily accessible, and affordable form of mental health support. However, sustained engagement with DMH is suboptimal, with limited research on DMH engagement. The Health Action Process Approach (HAPA) is an empirically supported theory of health behavior adoption and maintenance. Whether this model also explains DMH tool engagement remains unknown. ObjectiveThis study examined whether an adapted HAPA model predicted engagement with DMH via a self-guided website. MethodsVisitors to the Mental Health America (MHA) website were invited to complete a brief survey measuring HAPA constructs. This cross-sectional study tested the adapted HAPA model with data collected using voluntary response sampling from 16,078 sessions (15,619 unique IP addresses from United States residents) on the MHA website from October 2021 through February 2022. Model fit was examined via structural equation modeling in predicting two engagement outcomes: (1) choice to engage with DMH (ie, spending 3 or more seconds on an MHA page, excluding screening pages) and (2) level of engagement (ie, time spent on MHA pages and number of pages visited, both excluding screening pages). ResultsParticipants chose to engage with the MHA website in 94.3% (15,161/16,078) of the sessions. Perceived need (β=.66; P

# Background Limitations exist with current ACLR functional testing assessments that may be mitigated by including single-leg multi-directional testing. # Hypothesis/Purpose To compare Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI) scores, limb symmetry index (LSI) of the single-leg vertical jump (SLVJ), single-leg medial rotation hop (SLMRH), single-leg lateral hop (SLLH), and isokinetic quadriceps strength between participants with an ACLR and healthy controls and assess predictors of quadriceps strength asymmetry. It was hypothesized that ACL-RSI scores and LSIs for all tests would differ between ACLR and healthy control groups and within the ACLR group a strong correlation would exist between all outcome measures and quadriceps strength. # Study Design Cross-Sectional Study # Methods Twenty-six participants with an ACLR (median 13 months after surgery) and twenty-six matched healthy controls were recruited to participate in this study. Performance was assessed via SLVJ, SLMRH, SLLH, and isokinetic quadriceps strength. Between-group comparisons were made with independent t-tests and Mann-Whitney U test. Within the ACLR group, bivariate correlation and multivariate regression analysis were performed to assess the relationship between the outcome measures and quadriceps strength asymmetry. # Results Significant between-limb differences were only identified in the ACLR group (p< 0.05): SLVJ LSI: 88.5%, SLMRH LSI: 93.6%, SLLH LSI: 92.7%, quadriceps strength LSI 80.9% - 83.9%, which were significantly lower (p 0.05) correlation with quadriceps strength (r= 0.12-0.30). # Conclusion Single-leg multidirectional test LSIs were less in ACLR participants than matched healthy controls and all were directly related to quadriceps strength. Psychological readiness to return to sport was not related to quadriceps strength.

Introduction: Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice. Methods: A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020. Results: A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38). Conclusions: During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.

Gender-based violence (GBV) is prevalent in South Africa, primarily attributed to historical systems of social inequality, patriarchy and racism that dominated during the apartheid regimes, with lasting impacts persisting today. Thus, this study explored the intricate dynamics and prevalence of GBV in the context of South Africa. To realize this objective, the study employed a qualitative research methodology. To collect data, the study employed a secondary data technique such as a literature review of existing sources. Different datasets were used such as Google Scholar, National Institutes of Health, Google, and Scopus. The criterion employed to source information was the use of keywords which are shedding light on the social, cultural, and economic factors contributing to GBV. The study explored the root causes and manifestations of violence against women and girls. It is found that South Africa is grappling with high rates of GBV due to poverty, unemployment, cultural beliefs, and legal factors. To mitigate the prevalence and causes of GBV, efforts to combat GBV should encompass legal reforms and protection, prevention education, awareness, and NGO programmes that address the profoundness and complexity of violence against women and girls. The study has a vast potential to contribute to the production of new knowledge on forms, causes and mitigation measures for GBV. It will also contribute by addressing gaps or limitations in the existing literature on the phenomenon being studied.

Abstract: Introduction: This study analyzes the effects of personality traits on the stockpiling of groceries in the United Kingdom during the COVID–19 pandemic. The sample is representative of the UK population in terms of age, gender, and residential area. Methods: We collected the data through five rounds of web surveys during the spring of 2020 (N = 1025). We used the Big Five Inventory (BFI–10) to measure personality traits. We analyzed the data using independent t-tests and logistic regression. Results: The independent t-tests show that “stockpilers” have a higher degree of Neuroticism and a lower degree of Agreeableness and Conscientiousness than “nonstockpilers.” Logistic regressions moreover show that differences in Neuroticism are related to other personality traits, and that differences in Agreeableness are largely related to age and residential area. The low degree of Conscientiousness among “stockpilers” remains, after we controlled for other factors in the model (i.e., personality traits, gender, age, and residential area). Discussion: We discuss the findings regarding previous research. Understanding personality traits and stockpiling is important to prepare and manage similar extraordinary situations that may occur in the future.

Abstract Kelvin probe force microscopy (KPFM) is a well‐established scanning probe technique, used to measure surface potential accurately; it has found extensive use in the study of a range of materials phenomena. In its conventional form, KPFM frustratingly precludes imaging samples or scenarios where large surface potential or surface potential gradients exist outside the typical ±10 V window. If the potential regime measurable via KPFM can be expanded, to enable precise and reliable metrology, through a high voltage KPFM (HV‐KPFM) adaptation, it can open up pathways toward a range of novel experiments, where the detection limit of regular KPFM has so far prevented the use of the technique. In this work, HV‐KPFM is realized and shown to be capable of measuring large surface potential and potential gradients with accuracy and precision. The technique is employed to study a range of materials (positive temperature coefficient of resistivity ceramics, charge storage fluoropolymers, and pyroelectrics) where accurate, spatially resolved mapping of surface potential within high voltage regime facilitates novel physical insight. The results demonstrate that HV‐KPFM can be used as an effective tool to fill in existing gaps in surface potential measurements while also opening routes for novel studies in materials physics.

This study investigates the moderating role of stakeholder support in the relationship between supply chain integration and organizational resources and capabilities. This study collected two hundred and five usable responses from top and senior managers of brewery companies and their key suppliers. Structural equation modelling was used to assess the hypothesized causal paths. The findings indicate that stakeholder support positively moderates the relationship between supply chain integration and organizational resources, as well as the relationship between organizational resources and organizational capabilities. The study has demonstrated that the effect of supply chain integration on organizational resources and capabilities is contingent on the direct and indirect support from both primary and secondary stakeholders in the supply chain. This study contributes to the literature on supply chain management by providing insights into the moderating role of stakeholder support in the relationship between supply chain integration and organizational resources and capabilities. The study highlights the importance of stakeholder support in building the necessary capabilities for a firm to provide competitive services to its customers.

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Objective: To compare the basic airway management skill score of Thai medical students who learned airway management utilizing blended peer-to-peer teaching with those who learned by the standard face-to-face approach. The learners’ pre- and post-learning confidence, satisfaction with the learning, and stress levels were evaluated. Materials and Methods: A randomized crossover study was conducted with third-year medical students in Thailand. Basic airway management was taught, including oropharyngeal and nasopharyngeal airway insertion, and bag-mask ventilation skills. After the learning, two blinded and independent experts rated the learners on performing the procedures. Results: In total, 32 participants took part in the study. The blended group had significantly lower skill scores for oropharyngeal airway (8.69 ±1.078 and 9.69 ± 0.479, p-value 0.004) and nasopharyngeal airway (7.87 ± 1.408 and 9.38 ± 0.500, p-value 0.001) management, respectively. The bag-mask ventilation skills scores were also lower in the blended group. The confidence level was increased in both groups. Learning with the face-to-face method was found to be slightly less stressful. Overall, the majority of the students preferred learning by the standard method. Conclusion: Unlike Western students, Thai learners can learn basic airway management skills more effectively with the face-to-face instructor-led method than with the peer-oriented blended method.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p

Lithification of artificial ground comprising by-products of legacy iron and steel workings presents a range of opportunities including atmospheric carbon dioxide (CO2) storage. The natural environmental processes altering these waste sites can also pose challenges such as ecotoxic metal leaching, and so it is important to characterise these largely undocumented anthropogenically-derived rocks. This study documents the lithification mechanisms, as well as mineralogical and geochemical characteristics across a legacy coastal iron and steel slag deposit (in Warton, England). X-Ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) analysis of the slag deposit, as well as thermogravimetric analysis (TGA) of the cream-coloured material covering the deposit, shows lithification both on the top surface and the seaward side above the mean high-water mark (MHWM), which is the result of carbonate mineralisation. This process is driven by water weathering slag minerals (gehlenite, åkermanite, and pseudowollastonite), which release calcium (Ca). Ingassed and hydroxylated atmospheric CO2 reacts with the leached Ca to form calcite that is slightly to strongly depleted in 13C (δ13C values: -6.4 ‰ to -22.7 ‰), following partial dissolved inorganic carbonate (DIC) equilibrium. Calcium-silicate-hydrate (CSH) precipitation was responsible for lithifying the deposit where more frequent and abundant seawater washing prevents subsequent slag mineral dissolution and carbonate precipitation. This work shows that legacy iron and steel slag deposits are prone to lithification, particularly in coastal settings. This lithification can draw down atmospheric CO2 and has the potential to slow the release of toxic metals from CSH precipitation, enhancing the possibility for repurposing legacy industrial waste for CO2 storage and coastal defence applications.

This article recommends institutional changes to higher education related to time, learning, and risk that would better serve the contemporary student population and increase opportunities for life-long and interdisciplinary learning. To begin, the changing demographic of university students will be outlined, along with suggestions about how traditional institutional arrangements are no longer conducive to optimal learning environments. Next, a review of the history of the academic year will be provided, that will show a snapshot of post-secondary academic calendars in Canada. Relatedly, a discussion of the potential drawbacks and benefits to accelerated courses will be deliberated, as well as the role of risk in terms of how this shapes students’ course selection. Finally, an example of a pilot program at McMaster University, a large research-intensive university in Ontario, Canada, which is specifically designed to account for the pitfalls outlined above, will be discussed. Taken together, it will be argued that having full-course offerings on a year-round basis, providing various options for course lengths, and adjusting evaluations to reduce students’ conceptions of ‘risk’ will better adapt institutes of higher education for the twenty-first century.

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass the four types of ncRNAs associated with the disease. Our comprehensive search and analysis reveal that ncRNAs not only play crucial roles in the pathogenesis of AD but also hold potential as biomarkers for its early detection and as novel therapeutic targets. Specifically, the findings underscore the significance of miRNAs in regulating genes involved in key AD pathways such as activin receptor signaling pathway, actomyosin contractile ring organization, and advanced glycation endproducts-receptor advanced glycation endproducts (AGE-RAGE) signaling pathway. This review also highlights the potential of ncRNAs in unveiling novel diagnostic and therapeutic strategies, emphasizing the need for further research to validate their clinical utility. Our systematic exploration provides a foundation for future bioinformatic analyses and the development of ncRNA-based precision medicine approaches for AD, offering new insights into the disease’s molecular pathology and paving the way for innovative treatment strategies.Systematic review registrationPROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42022355307.

Abstract Urban evolutionary ecology is inherently interdisciplinary. Moreover, it is a field with global significance. However, bringing researchers and resources together across fields and countries is challenging. Therefore, an online collaborative research hub, where common methods and best practices are shared among scientists from diverse geographic, ethnic, and career backgrounds would make research focused on urban evolutionary ecology more inclusive. Here, we describe a freely available online research hub for toolkits that facilitate global research in urban evolutionary ecology. We provide rationales and descriptions of toolkits for: (1) decolonizing urban evolutionary ecology; (2) identifying and fostering international collaborative partnerships; (3) common methods and freely‐available datasets for trait mapping across cities; (4) common methods and freely‐available datasets for cross‐city evolutionary ecology experiments; and (5) best practices and freely available resources for public outreach and communication of research findings in urban evolutionary ecology. We outline how the toolkits can be accessed, archived, and modified over time in order to sustain long‐term global research that will advance our understanding of urban evolutionary ecology.

Background: The effects of climate change are major threats to health and well-being. While the profession of pharmacy can make a difference through patient care activities or sustainability and advocacy efforts, literature detailing U.S. pharmacist and student pharmacist views on this topic is scant. Objectives: To assess Ohio pharmacy interns’ knowledge and beliefs regarding climate change and human health as well as its relevance to pharmacy practice and education, and to compare and contrast their perceptions with those of Ohio pharmacists previously surveyed. Methods: An anonymous 31-item electronic survey was emailed to a random sample of 500 pharmacy interns registered in Ohio with questions regarding climate change and health, climate change policy, potential roles for pharmacists and pharmacy interns, pharmacy education, and selected demographics. Data were analyzed using descriptive and nonparametric statistics, and responses collected from this study were compared with those from the Ohio pharmacist study conducted the previous year. Results: Ninety-two interns completed the survey. The majority of respondents thought climate change is happening (87%), will harm human health in their community (68%), and is relevant to pharmacists or pharmacy practice (62%). Compared to registered pharmacists, pharmacy interns more often acknowledged these statements and more often identified roles in climate action. Sixty-two percent somewhat or strongly agreed that there should be more education about climate change and health in the pharmacy curriculum. Conclusion: Ohio pharmacy interns participating in this survey recognized the impact of climate change on health, believed they roles in mitigating its effects, and wanted to learn more about it. As these are the first data assessing U.S. pharmacy interns’ perceptions of this topic, additional studies should be performed in other parts of the country. Increased education among student pharmacists may help propel the pharmacy profession to become a leader in climate action and sustainability.

ABSTRACT Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N′-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.IMPORTANCEThis paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

Coastal water level information is crucial for understanding flood occurrences and changing risks. Here, we validate the preliminary version (0.9) of NOAA’s Coastal Ocean Reanalysis (CORA), which is a 43-year reanalysis (1979–2021) of hourly coastal water levels for the Gulf of Mexico and Atlantic Ocean (i.e., the Gulf and East Coast region, or GEC). CORA-GEC v0.9 was conducted by the Renaissance Computing Institute using the coupled ADCIRC+SWAN coastal circulation and wave model. The model uses an unstructured mesh of nodes with varying spatial resolution that averages 400 m near the coast and is much coarser in the open ocean. Water level variations associated with tides and meteorological forcing are explicitly modeled, while lower-frequency water level variations are included by dynamically assimilating observations from NOAA’s National Water Level Observation Network. We compare CORA to water level observations that were either assimilated or not, and find that the reanalysis generally performs better than a state-of-the-art global ocean reanalysis (GLORYS12) in capturing the variability on monthly, seasonal, and interannual timescales as well as the long-term trend. The variability of hourly non-tidal residuals is also shown to be well resolved in CORA when compared to water level observations. Lastly, we present a case study of extreme water levels and coastal inundations around Miami, Florida to demonstrate an application of CORA for studying flood risks. Our assessment suggests that NOAA’s CORA-GEC v0.9 provides valuable information on water levels and flooding occurrence from 1979–2021 in areas that are experiencing changes across multiple time scales. CORA potentially can enhance flood risk assessment along parts of the U.S. Coast that do not have historical water level observations.

Advanced cholangiocarcinoma (CCA) presents a clinical challenge due to limited treatment options, necessitating exploration of innovative therapeutic approaches. Bispecific T cell engager (BTE)-armed T cell therapy shows promise in hematological and solid malignancies, offering potential advantages in safety over continuous BTE infusion. In this context, we developed a novel BTE, targeting CD3 on T cells and integrin αvβ6, an antigen elevated in various epithelial malignancies, on cancer cells. The novel BTE was generated by fusing an integrin αvβ6-binding peptide (A20) to an anti-CD3 (OKT3) single-chain variable fragment (scFv) through a G4S peptide linker (A20/αCD3 BTE). T cells were then armed with A20/αCD3 BTE (A20/αCD3-armed T cells) and assessed for antitumor activity. Our results highlight the specific binding of A20/αCD3 BTE to CD3 on T cells and integrin αvβ6 on target cells, effectively redirecting T cells towards these targets. After co-culture, A20/αCD3-armed T cells exhibited significantly heightened cytotoxicity against integrin αvβ6-expressing target cells compared to unarmed T cells in both KKU-213A cells and A375.β6 cells. Moreover, in a five-day co-culture, A20/αCD3-armed T cells demonstrated superior cytotoxicity against KKU-213A spheroids compared to unarmed T cells. Importantly, A20/αCD3-armed T cells exhibited an increased proportion of the effector memory T cell (Tem) subset, upregulation of T cell activation markers, enhanced T cell proliferation, and increased cytolytic molecule/cytokine production, when compared to unarmed T cells in an integrin αvβ6-dependent manner. These findings support the potential of A20/αCD3-armed T cells as a novel therapeutic approach for integrin αvβ6-expressing cancers.

Introduction: Voluntary medical male circumcision (VMMC) is one of the key interventions against heterosexual spread of HIV. However, its prevalence in South Sudan is not clearly understood. This study aimed to assess the prevalence and perceptions of VMMC among University of Juba students. Method: A cross sectional descriptive study design was adopted. Data from randomly selected students from six schools of the University of Juba were collected using a respondent-administered structured questionnaire. IBM SPSS Statistics version 23.0 was used for data analysis. Chi-squared tests were performed to determine variables significantly associated with VMMC. Results: Amongst 390 students interviewed, the prevalence of VMMC was 41.8% and the overall male circumcision rate was 83.8%. Most respondents expressed positive attitudes and perceptions towards VMMC. The respondents believe VMMC is an important health programme. The decision to get circumcised is associated with age, marital status, religion and state of origin (p

Abstract Background In Kenya, diarrhoeal disease is the third leading cause of child mortality after malaria and pneumonia, accounting for nearly 100 deaths daily. We conducted a cross-sectional study in Mukuru informal settlements to determine the bacteria associated with diarrhea and their ASTs to provide data essential for implementing appropriate intervention measures. Methods Diarrheagenic children (≤ 5 years) were purposively recruited from outpatient clinics of Municipal City Council, Mukuru kwa Reuben, Medical Missionaries of Mary, and Mama Lucy Kibaki Hospital, Nairobi. A total of 219 stool samples were collected between May 2021 and August 2021. Stool culture was done on MacConkey and Salmonella Shigella agar, while the recovered bacteria were identified using VITEK®2GNID and polymerase chain reaction (PCR) used for E. coli pathotyping. Antibiotic Susceptibility Testing was done using VITEK®2AST-GN83. Results At least one bacterial organism was recovered from each of the 213 (97%) participants, with 115 (56%) participants having only one bacterial type isolated, 90 (43%) with two types of bacteria, and 2 (1%) with three types of bacteria recovered. The most predominant bacteria recovered was 85% (93/109) non-pathogenic E.coli and 15% (16/109)of pathogenic E.coli, with 2 (1%) were Enterohemorrhagic E.coli (EHEC), 6 (3%) were Enteroaggregative E.coli (EAEC), and 8 (4%) were Enteropathogenic E.coli (EPEC). Other potentially pathogenic bacteria included Enterobacter sp (27.8%), Klebsiella sp 33(11%), and Citrobacter sp 15(4.7%). Pathogenic isolates such as Salmonella 7 (2%), Proteus mirabilis 16 (6%), Providencia alcalifaciens 1 (0.3%), and Shigella 16 (4.7%) were detected. Isolates such as Pantoea spp 2(0.67%), Raoultella planticola 1(0.33%), and Kluyvera 6(2%) rarely reported but implicated with opportunistic diarrhoeal disease were also recovered. Ampicillin, cefazolin, and sulfamethoxazole-trimethoprim were the least effective antimicrobials at 64%, 57%, and 55% resistance, respectively, while meropenem (99%), amikacin (99%), tazobactam piperacillin (96%), and cefepime (95%) were the most effective. Overall, 33(21%) of all enterics recovered were multidrug-resistant. Conclusion The study documented different bacteria potentially implicated with childhood diarrhea that were not limited to E. coli, Shigella, and Salmonella, as previously observed in Kenya. The strains were resistant to the commonly used antibiotics, thus narrowing the treatment options for diarrheal disease.

Abstract Background Critical illness is a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and potential for reversibility. The burden of critical illness is high, especially in low- and middle-income countries. Critical care can be provided as Essential Emergency and Critical Care (EECC)– the effective, low-cost, basic care that all critically ill patients should receive in all parts of all hospitals in the world– and advanced critical care– complex, resource-intensive care usually provided in an intensive care unit. The required resources may be available in the hospital and yet not be ready in the wards for immediate use for critically ill patients. The ward readiness of these resources, although harder to evaluate, is likely more important than their availability in the hospital. This study aimed to assess the ward readiness for EECC and the hospital availability of resources for EECC and for advanced critical care in hospitals in Tanzania. Methods An in-depth, cross-sectional study was conducted in five purposively selected hospitals by visiting all wards to collect data on all the required 66 EECC and 161 advanced critical care resources. We defined hospital-availability as a resource present in the hospital and ward-readiness as a resource available, functioning, and present in the right place, time and amounts for critically ill patient care in the wards. Data were analyzed to calculate availability and readiness scores as proportions of the resources that were available at hospital level, and ready at ward level respectively. Results Availability of EECC resources in hospitals was 84% and readiness in the wards was 56%. District hospitals had lower readiness scores (less than 50%) than regional and tertiary hospitals. Equipment readiness was highest (65%) while that of guidelines lowest (3%). Availability of advanced critical care resources was 31%. Conclusion Hospitals in Tanzania lack readiness for the provision of EECC– the low-cost, life-saving care for critically ill patients. The resources for EECC were available in hospitals, but were not ready for the immediate needs of critically ill patients in the wards. To provide effective EECC to all patients, improvements are needed around the essential, low-cost resources in hospital wards that are essential for decreasing preventable deaths.

Abstract Waves are omnipresent in avalanches on Earth and other planets. The dynamic nature of waves makes them dangerous in geological hazards such as debris flows, turbidity currents, lava flows, and snow avalanches. Extensive research on granular waves has been carried out by using theoretical and numerical approaches with idealized assumptions. However, the mechanism of waves in realistic complex situations remains intangible, as it is notoriously difficult to capture complex granular waves on real terrain. Here, we leverage a recently developed hybrid Eulerian-Lagrangian numerical scheme and an elastoplastic constitutive model to investigate the processes involved in waves of snow avalanches, including erosion, deposition, and flow instability induced by terrain irregularity. This enables us to naturally simulate roll-waves, erosion-deposition waves, and their transitions in a single large-scale snow avalanche on real terrain. Simulated wave features show satisfactory consistency with field data obtained with different radar technologies. Based on a dimensionless analysis, the wave mechanics is not only controlled by the Froude number and local topography but also by the mass of the wave which governs the entrainment propensity. This study offers new insights into wave mechanisms of snow avalanches and provides a novel and promising pathway for exploring transient waves in granular mass movements.

Breast cancer is the most common malignant tumour in women in the world, with an incidence of 13.5% in India. For patients diagnosed with breast cancer, surgical options include breast conserving therapy (BCT) or modified radical mastectomy (MRM). This study aims to compare early post-operative complications in carcinoma breast patients undergoing MRM vs BCS at a tertiary care center in India. Patients undergoing BCS and MRM for carcinoma breast were prospectively studied over an 18-month period and postoperatively followed up for 3 months. Incidence of early post-operative complications such as seroma, flap necrosis, wound dehiscence and quality of life (QOL) were compared between the two groups. 106 patients were included in this study, of which 75 underwent MRM and 31 underwent BCS. There was no significant difference noted between these two groups with respect to the following; seroma formation (16.1% BCS vs. 13.3% MRM; p value =0.710), flap necrosis (3.2% vs. 2.7%; p value =0.87), wound dehiscence (3.2% vs. 5.3%; p value =0.63), wound infection (6.5% vs. 5.3% p value =0.823), average number of days of lymphorrhoea (15 ±9.76 vs. 15.7 ±7.49) and QOL post-surgery. Comparison of cost (> Rs.50,000) showed that expense of surgical treatment was significantly higher in MRM (24.0%) compared to BCS (9.7%). Early postoperative complications seen in BCS and MRM are comparable, with the most common early complication being seroma and lymphorroea. Patients should be educated regarding breast conservative surgery, its comparable results with MRM and social and physical impact irrespective of age and menstrual status.

Steel slit damper (SSD) is specifically engineered to absorb and disperse energy to mitigate the possibility of structural damage and collapse during seismic events. However, the effectiveness of these dampers are compromised due to wear, corrosion and other forms of material degradation and failure mechanisms. For this reason, it is important to consistently monitor its condition and conduct maintenance and repairs to guarantee safety and dependability of the structures it is installed with. Now, vibration-based techniques have emerged as a promising structural health monitoring (SHM) strategy. It involves methodologies for detecting changes in functions and analyzing vibrations to discover potential problems. This study entails a comprehensive examination of the most recent advancements and breakthroughs in vibration-based methodologies used in SHM. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), we identified several key techniques and technologies that show promise in enhancing the maintenance and monitoring of steel– or steel and metal surfaces- slit dampers. The pros and cons of these methods are presented to be applicable when monitoring an SSD. This paper presents notable figures and their corresponding discussions to achieve enhanced understanding of the advancements in SHM towards sensor technologies, monitoring techniques, and applications in civil infrastructure. Furthermore, this paper reviews the applications and functions framework for real-time SHM of SSDs together with their practical implementations and applications using diverse monitoring technologies to promote innovation. Finally, the optimal sensor selection criteria, data gathering methodologies, experimental settings, innovative approaches with comparative analyses, and a proposed maintenance standard for SSDs are described in this study.

Purpose: To evaluate and correlate the structural changes between peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) + inner plexiform layer (IPL) in different stages of glaucoma using PanoMap® optical coherence tomography (OCT). Design: Retrospective observational study. Methods: Glaucoma diagnostic test data were collected from early to moderate open-angle glaucoma patients. The average and minimum GCL + IPL thickness, sectoral GCL + IPL thickness, and the average and sectoral RNFL thickness were correlated with the different glaucoma stages. Results: This study included 157 eyes from 157 glaucoma patients. Patients were grouped into pre-perimetric, early, and moderate glaucoma. The mean average RNFL thickness, RNFL thickness per sector, average GCL + IPL thickness, and minimum GCL + IPL thickness were different between the three groups (P < 0.001), except for the nasal sector (P = 0.643).The mean GCL + IPL thickness in all six sectors showed differences between the groups (P < 0.001), except the superonasal sector (P < 0.002).The inferior GCL + IPL sector is the thinnest, followed by the inferotemporal sector. There was a strong correlation between the mean average RNFL and the average GCL + IPL thickness in the pre-perimetric group (r = 0.4963, P < 0.001) and the moderate group (r = 0.6534, P < 0.001).The early glaucoma group did not show significant correlation (r = 0.2963, P = 0.0536). Conclusion: Peripapillary RNFL and macular GCL + IPL thinning was evident in different stages of glaucoma, with more thinning observed with increasing glaucoma severity. The peripapillary RNFL and macular GCL + IPL average thickness values were highly correlated in the pre-perimetric and moderate stages of glaucoma.

Abstract Background The Russian Federation’s invasion of Ukraine is characterized by indiscriminate attacks on civilian infrastructure, including hospitals and clinics that have devastated the Ukrainian health system putting trauma care at risk. International healthcare providers responded to the need for help with the increasing numbers of trauma patients. We aimed to describe their experiences during the conflict to explore the gaps in systems and care for trauma patients to refine the Global Trauma System Evaluation Tool (G-TSET) tool. Methods We conducted qualitative key informant interviews of healthcare providers and business and logistics experts who volunteered since February 2022. Respondents were recruited using purposive snow-ball sampling. Semi-structured, in-depth interviews were conducted virtually from January-March 2023 using a modified version of the G-TSET as an interview guide. Interviews were transcribed verbatim and deductive thematic content analysis was conducted using NVivo. Findings We interviewed a total of 26 returned volunteers. Ukraine’s trauma system is outdated for both administrative and trauma response practices. Communication between levels of the patient evacuation process was a recurrent concern which relied on handwritten notes. Patient care was impacted by limited equipment resources, such as ventilators, and improper infection control procedures. Prehospital care was described as highly variable in terms of quality, while others witnessed limited or no prehospital care. The inability to adequately move patients to higher levels of care affected the quality of care. Infection control was a key issue at the hospital level where handwashing was not common. Structured guidelines for trauma response were lacking and lead to a lack of standardization of care and for trauma. Although training was desired, patient loads from the conflict prohibited the ability to participate. Rehabilitation care was stated to be limited. Conclusion Standardizing the trauma care system to include guidelines, better training, improved prehospital care and transportation, and supply of equipment will address the most critical gaps in the trauma system. Rehabilitation services will be necessary as the conflict continues into its second year.

Abstract Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood–brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showcasing its remarkable antioxidative and anti-inflammatory properties, its ability to fortify the BBB and its direct influence on neural preservation and adaptability. These diverse effects collectively translate into enhancements in both motor and cognitive functions. This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and cognitive impairment associated with diabetes.

Acquired perforating dermatosis (APD) is an adult skin disease characterized by an umbilicated papulonodular rash with transepidermal elimination of dermal components such as collagen and/or elastin. It is frequently associated with multiple medications and diseases such as diabetes and chronic renal failure. It is a disabling disease with severe pruritus in 83.3% of cases and generalized ulcerating lesions that are associated with infections and scarring. Nearly 10% of renal patients are affected. Supportive measurements of disease activity and previous medications failed to halt its natural progression. In our study, we documented significant improvements in the severity of the disease as measured by the eczema area and severity index (EASI), in 32 patients with the renal disease through the use of mycophenolate mofetil (MMF), with EASI decreasing from 31 [interquartile range (IQR) = 4] to 3 (IQR = 4) by the 3rd month. Moreover, such changes persisted for up to 2 years despite a decrease in the dose of MMF to half after 1 year. In conclusion, our study showed that MMF is a safe and effective immunosuppressive drug for short- and intermediate-term therapy of severe APD and confirmed its autoimmune etiology.

The data available on immunoglobulin A (IgA) deposition disease indicate an inherited predisposition to the disease with autoimmune triggering. Hence, we prospectively evaluated the role of a new autoimmune regimen in the treatment of severe nephrotic or nephritic flares associated with noncrescentic nephritis in adult patients. Thirty-six patients were included, and the regimen consisted of an initial 3-month induction phase of prednisone and mycophenolate mofetil (MMF), followed by a maintenance phase of MMF alone for 21 months. Complete remission (CR) (normalization of creatinine clearance [CrCl] and a decrease in protein output to

Abstract Understanding antibiotic use in dairy systems is critical to guide antimicrobial stewardship programs. We investigated antibiotic use practices in small-holder dairy farms, antibiotic quality, and antimicrobial resistance (AMR) awareness among veterinary drug retailers in a mixed farming community in the central Kenyan highlands. Data were collected from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. A scale was developed to measure knowledge about AMR and antibiotic use using item response theory, and regression models were used to evaluate factors associated with antibiotic use and AMR knowledge. The active pharmaceutical ingredient (API) content of 27 antibiotic samples was determined using high-performance liquid chromatography (HPLC). The presence and levels of 11 antibiotic residues in 108 milk samples collected from the study farms were also investigated using liquid chromatography tandem mass spectrometry (LC–MS/MS). Almost all farms (98.8%, n = 244) reported using antibiotics at least once in the last year, mostly for therapeutic reasons (35.5%). The most used antibiotics were tetracycline (30.6%), penicillin (16.7%), and sulfonamide (9.4%), either individually or in combination, and predominantly in the injectable form. Larger farm size (OR = 1.02, p

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice. Résumé: La douleur ou la gêne thoracique sont des symptômes fréquents qui peuvent poser un dilemme diagnostique pour de nombreux médecins. Les erreurs de diagnostic d’une cause aiguë ou chronique progressive d’origine cardiaque peuvent d'ailleurs entraîner un risque considérable de morbidité et de mortalité. La présente synthèse porte sur les différentes options et modalités d’établissement du diagnostic et de la gravité d’une coronaropathie. Un algorithme efficace pour le choix des tests doit être adapté à chaque patient afin de maximiser l’exactitude diagnostique dans les plus brefs délais, de déterminer le pronostic à court et à long terme, et de permettre une mise en œuvre de traitements fondés sur des données probantes tout en tenant compte des coûts. Un algorithme décisionnel a donc été conjointement mis au point (www.chowmd.ca/cadtesting) et pourrait être largement adopté dans la pratique clinique.

Abstract Objectives Autologous dentin grafts derived from extracted teeth have shown promise as bone graft materials for promoting bone regeneration. This retrospective case series aimed to evaluate clinical, radiographic, and histologic outcomes of using autologous dentin matrices in various bone regeneration procedures. Materials and Methods This case series included 26 eligible patients and encompassed 4 socket preservation cases, 5 cases of guided tissue regeneration, 5 cases of guided bone regeneration (GBR), 10 cases of sinus augmentation procedures, 2 immediate placement implants, and 2 socket shields. Dentin grafts were prepared from extracted teeth, cleaned, and processed. These grafts were combined with platelet‐rich fibrin (PRF) to create adhesive dentin matrices, then covered with collagen membranes for simultaneous guided bone augmentation cases. Cone beam computed tomography (CBCT) scans were conducted before surgery and 4 months postoperatively to assess ridge dimensions. Histologic evaluation was performed through bone core biopsies for socket preservation cases at the 4‐month mark. Results A total of 42 implants were placed in 26 patients, with an average follow‐up of 32 months. Notably, two implant failures occurred following lateral maxillary sinus augmentation. CBCT scans at the 4‐month interval revealed bone coverage over implant platforms in the majority of cases. Histologic analysis from two cases of socket preservation demonstrated dentin granules enveloped by newly formed bone undergoing continuous remodeling. The quantitative histomorphometric assessment revealed a bone area of 42.8 ± 3.56%, a remaining graft area of 19.05 ± 4.58%, and a viable bone of 38.15 ± 7.84%. Conclusions The utilization of autologous dentin particles mixed with PRF proved effective as an alternative to conventional bone graft materials in GBR and maxillary sinus augmentation procedures. Larger controlled clinical trials are recommended to further substantiate these findings.

Abstract Despite numerous qualitative and cross-sectional studies investigating how dog-related factors may impact owners’ well-being, empirical studies to test these causal effects are lacking. This prospective cohort study examined the correlation and potential causal effect of 17 dog-related factors with six well-being outcomes (depression, anxiety, loneliness, suicidal ideation, hedonic well-being and eudaimonic well-being) in dog owners. Over a four-week period, 709 adult dog owners reported their weekly well-being and occurrence of each dog-related factor (e.g. how many times they ran with their dogs). A random intercept cross-lagged panel model (RI-CLPM) with significance threshold set at 0.001 was used. Six factors correlated with poorer owner well-being (i.e. aggressive dog behaviour, fearful dog behaviour, poor dog health, failure to provide for the dog, lack of control over the dog, and dog presence). Only ‘friendly conversation with others due to the dog’ correlated with better well-being. Purposeful reductions in the frequency of dog behavioural and health-related issues are likely to improve owner well-being, as well as greater consistency in dog care (i.e. provide for the dog) and more engagement in friendly dog-facilitated social interactions. No potential causal effects were significant. Further studies investigating causal relationships are essential to improve people’s well-being through dog ownership.

Abstract Background Germ Defence ( www.germdefence.org ) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19, the intervention needed to be implemented at scale rapidly. Methods With NHS England approval, we conducted an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via general practitioner (GP) practices across England, UK, compared with usual care to disseminate Germ Defence to patients. GP practices randomised to the intervention arm (n = 3292) were emailed and asked to disseminate Germ Defence to all adult patients via mobile phone text, email or social media. Usual care arm GP practices (n = 3287) maintained standard management for the 4-month trial period and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses and suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage and hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of the intervention by GP practice and by patients was measured via website analytics. Results Germ Defence was used 310,731 times. The average website satisfaction score was 7.52 (0–10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95% CI 0.96, 1.06, p = 0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0 to 48% of a practice list. Conclusions While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment. Trial registration This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.

Abstract Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. Results The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. Conclusions This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration www.ClinicalTrials.gov NCT03374800. November 21, 2017.

Background Approximately 20% of patients who are discharged from hospital for an acute exacerbation of COPD (AECOPD) are readmitted within 30 days. To reduce this, it is important both to identify all individuals admitted with AECOPD and to predict those who are at higher risk for readmission. Objectives To develop two clinical prediction models using data available in electronic medical records: 1) identifying patients admitted with AECOPD and 2) predicting 30-day readmission in patients discharged after AECOPD. Methods Two datasets were created using all admissions to General Internal Medicine from 2012 to 2018 at two hospitals: one cohort to identify AECOPD and a second cohort to predict 30-day readmissions. We fit and internally validated models with four algorithms. Results Of the 64,609 admissions, 3,620 (5.6%) were diagnosed with an AECOPD. Of those discharged, 518 (15.4%) had a readmission to hospital within 30 days. For identification of patients with a diagnosis of an AECOPD, the top-performing models were LASSO and a four-variable regression model that consisted of specific medications ordered within the first 72 hours of admission. For 30-day readmission prediction, a two-variable regression model was the top performing model consisting of number of COPD admissions in the previous year and the number of non-COPD admissions in the previous year. Conclusion We generated clinical prediction models to identify AECOPDs during hospitalization and to predict 30-day readmissions after an acute exacerbation from a dataset derived from available EMR data. Further work is needed to improve and externally validate these models.

Introduction: Variable transplant-related knowledge may contribute to inequitable access to living donor kidney transplant (LDKT). We compared transplant-related knowledge between African, Caribbean, and Black (ACB) versus White Canadian patients with kidney failure using the Knowledge Assessment of Renal Transplantation (KART) questionnaire. Methods: This was a cross-sectional cohort study. Data were collected from a cross-sectional convenience sample of adults with kidney failure in Toronto. Participants also answered an exploratory question about their distrust in the kidney allocation system. Clinical characteristics were abstracted from medical records. The potential contribution of distrust to differences in transplant knowledge was assessed in mediation analysis. Results: Among 577 participants (mean [SD] age 57 [14] years, 63% male), 25% were ACB, and 43% were White Canadians. 45% of ACB versus 26% of White participants scored in the lowest tertile of the KART score. The relative risk ratio to be in the lowest tertile for ACB compared to White participants was 2.22 (95% confidence interval [CI]: 1.11, 4.43) after multivariable adjustment. About half of the difference in the knowledge score between ACB versus White patients was mediated by distrust in the kidney allocation system. Conclusion: Participants with kidney failure from ACB communities have less transplant-related knowledge compared to White participants. Distrust is potentially contributing to this difference.

Background Shoulder Injury Related to Vaccine Administration (SIRVA) is a preventable adverse event following incorrect vaccine administration, which can result in significant long-term morbidity. There has been a notable surge in reported cases of SIRVA as a rapid national population-based COVID-19 immunization program has been rolled out across Australia. Methods Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) in Victoria identified 221 suspected cases of SIRVA following the commencement of the COVID-19 vaccination program, reported between February 2021 and February 2022. This review describes the clinical features and outcomes of SIRVA in this population. Additionally, a suggested diagnostic algorithm is proposed, in order to facilitate early recognition and management of SIRVA. Results 151 cases were confirmed as SIRVA, with 49.0% having received vaccines at state vaccination centers. 75.5% were suspected incorrect administration site, with most patients experiencing shoulder pain and restricted movement within 24 hours of vaccination, lasting on average 3 months. Conclusion Improved awareness and education regarding SIRVA is imperative in a pandemic vaccine roll-out. The development of a structured framework for evaluating and managing suspected SIRVA will aid in timely diagnosis and treatment, essential to mitigate potential long-term complications.

The capacity of schools to address behavioral health concerns presents an emerging challenge, exacerbated by major shortages in the workforce. Schools across the U.S. are struggling to hire licensed behavioral health professionals, with additional barriers encountered when seeking to hire practitioners with experience in educational settings. In 2023, a school district in the suburbs of Columbus, Ohio, partnered with The Ohio State University to launch a “grow your own” policy pilot. The priorities focused on addressing workforce shortages and leveraging the experiences of current teachers/staff to support growing needs related to student mental health and well-being. More specifically, the district utilized COVID-19 relief funds to recruit, train, and transition 25 teachers/staff into school mental health positions by underwriting the costs of each professional’s Master of Social Work (MSW) degree. Here, we (a) describe the district–university partnership and the processes guiding the implementation of the “grow your own” model, (b) distill preliminary findings about district needs regarding behavioral health, and (c) explore facilitators, barriers, and outcomes associated with learning among participants in the program. The findings from a district-wide staff survey indicated a high level of need for individual counseling, crisis intervention, and small group interventions. Additionally, qualitative interviews revealed that learning among the program’s participants was facilitated by effective classroom strategies and specific learning experiences integral to the program’s design. These facilitators supported key learning outcomes, including general social work knowledge, self-awareness, and therapeutic skills that are foundational for engaging with students, parents/families, teachers/staff, and the broader school community. This innovative policy pilot and training model demonstrate how universities and local educational agencies can partner to address workforce development challenges at the intersection of behavioral health and education.