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Abstract Background In this “Advancing simulation practice” article, we offer an expose of the involvement of real patients in Objective Structured Clinical Examinations (OSCEs), inviting educators who traditionally involve solely SPs in their summative OSCEs to consider the practice. The need for standardisation in summative assessments can make educators understandably wary to try this, even if the rhetoric to involve real patients is accepted. We offer this as an instance of the tussle between standardisation and validity experienced throughout health professions education. Main text We offer our experience and empirical evidence of this simulation practice, based on an institutional ethnographic examination of the involvement of real patients in summative OSCEs from an undergraduate medical school in the UK. Our critique demonstrates the merits of this approach as an assessment environment closer to the real clinical environments where these soon-to-be doctors interact in a more authentic way with real patients and their illness experiences. We balance this against the extra work required for all involved and suggest the biggest challenge is in the reorientation work required for both Faculty and students who are institutionalised to expect standardisation above all in assessment. Conclusion We advocate for involving real patients in summative OSCEs and hope that readers may feel compelled and empowered to foster this shift in mindset required to introduce this practice into their assessments.

The Gulf of Mexico supports many seabird species, yet data gaps describing species composition and habitat use are prevalent. We used vessel-based observations from the Gulf of Mexico Marine Assessment Program for Protected Species to identify and characterize distinct seabird assemblages in the northern Gulf of Mexico (within the U.S. Exclusive Economic Zone; nGoM). Using cluster analysis of 17 seabird species, we identified assemblages based on seabird relative density. Vessel-based surveys documented the location, species, and number of seabirds across the nGoM between 2017-2019. For each assemblage, we identified the (co-)dominant species, spatial distribution, and areas of greater relative density. We also assessed the relationship of the total relative density within each assemblage with environmental, spatial, and temporal covariates. Of the species assessed, 76% (n = 13) breed predominantly outside the nGoM basin. We identified four seabird assemblages. Two assemblages, one dominated by black tern and the other co-dominated by northern gannet/laughing gull, occurred on the continental shelf. An assemblage dominated by sooty tern occurred along the continental slope into pelagic waters. The fourth assemblage had no dominant species, was broadly distributed, and was composed of observations with low relative density ('singles' assemblage). Differentiation of assemblages was linked to migratory patterns, residency, and breeding location. The spatial distributions and relationships of the black tern and northern gannet/laughing gull assemblages with environmental covariates indicate associations with river outflows and ports. The sooty tern assemblage overlapped an area prone to mesoscale feature formation. The singles assemblage may reflect commuting and dispersive behaviors. These findings highlight the importance of seasonal migrations and dynamic features across the seascape, shaping seabird assemblages. Considering the potential far-ranging effects of interactions with seabirds in the nGoM, awareness of these unique patterns and potential links with other fauna could inform future monitoring, research, restoration, offshore energy, and aquaculture development in this highly industrialized sea.

ObjectiveTo investigate the association between denture wearing and airflow limitation in men in Northern Ireland enrolled in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study.MethodsA case-control design was used to study partially dentate men. Cases were men aged 58-72 years who were confirmed as denture wearers. Controls were never denture wearers who were matched by age (± 1 month) and smoking habit to the cases. The men had a periodontal assessment and completed a questionnaire detailing their medical history, dental history and behaviours, social circumstances, demographic background and tobacco use. Physical examination and spirometry measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were also undertaken. Spirometry data for edentulous men who wore complete dentures were compared with that recorded for the partially dentate men studied.ResultsThere were 353 cases who were partially dentate and were confirmed denture wearers. They were matched for age and smoking habit to never denture wearer controls. The cases had an FEV1 that was on average 140 ml lower than the controls, p = 0.0013 and a 4% reduction in percent predicted FEV1, p = 0.0022. Application of the GOLD criteria indicated that 61 (17.3%) of the cases had moderate to severe airflow limitation compared with 33 (9.3%) of controls, p = 0.0051. Fully adjusted multivariable analysis showed that partially dentate men who were denture wearers were significantly more likely (p = 0.01) to have moderate to severe airflow reduction with an adjusted odds ratio (OR) of 2.37 (95% confidence intervals 1.23-4.55). In the 153 edentulous men studied moderate to severe airflow limitation was recorded in 44 (28.4%), which was significantly higher than in the partially dentate denture wearers (p = 0.017), and the men who had never worn a denture (pConclusionDenture wearing was associated with an increased risk of moderate to severe airflow limitation in the cohort of middle-aged Western European men studied.

Objective To compare and identify risk factors for distal adding-on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by anterior- (ASF) and posterior spinal fusion (PSF) to L3. Methods AIS patients undergoing ASF versus PSF to L3 from 2000–2010 were analyzed. Distal AO and DJK were deemed poor radiographic results. New stable (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores. Results Twenty of 42 (ASF group: 47.6%) and 8 of 72 patients (PSF group: 11.1%) showed poor radiographic outcome. Fused vertebrae, correction rate of main curve, coronal reduction rate of L3 were significantly higher in PSF group. Multiple logistic regression results indicated that preoperative SV-3 at L3 in standing and side benders (odds ratio [OR], 2.7 and 3.7, respectively), TS score -5, -6 at L3 (OR, 4.9), rigid disc at L3–4 (OR, 3.7), lowest instrumented vertebra (LIV) rotation > 15° (OR, 3.3), LIV deviation > 2 cm from center sacral vertical line (OR, 3.1) and ASF (OR, 13.4; p

The northern Gulf of Mexico (nGoM) is a globally important region for oil extraction and supports a diverse assemblage of marine birds. Due to their frequent contact with surface waters, diverse foraging strategies, and the ease with which oil adheres to feathers, seabirds are particularly susceptible to hydrocarbon contamination. Given the chronic and acute exposure of seabirds to oiling and a lack of studies that focus on the exposure of seabirds to oiling in sub-tropical and tropical regions, a greater understanding of the vulnerability of seabirds to oil in the nGoM appears warranted. We present an oil vulnerability index for seabirds in the nGoM tailored to the current state of knowledge using new, spatiotemporally expensive vessel-based seabird observations. We use information on the exposure and sensitivity of seabirds to oil to rank seabird vulnerability. Exposure variables characterized the potential to encounter oil and gas (O&G). Sensitivity variables characterized the potential impact of seabirds interacting with O&G and are related to life history and productivity. We also incorporated uncertainty in each variable, identifying data gaps. We found that the percent of seabirds’ habitat defined as highly suitable within 10 km of an O&G platform ranged from 0%-65% among 24 species. Though O&G platforms only overlap with 15% of highly suitable seabird habitat, overlap occurs in areas of moderate to high vulnerability of seabirds, particularly along the shelf-slope. Productivity-associated sensitivity variables were primarily responsible for creating the gradient in vulnerability scores and had greater uncertainty than exposure variables. Highly vulnerable species (e.g., Northern gannet (Morus bassanus)) tended to have high exposure to the water surface via foraging behaviors (e.g., plunge-diving), older age at first breeding, and an extended incubating and fledging period compared to less vulnerable species (e.g., Pomarine jaeger (Stercorarius pomarinus)). Uncertainty related to productivity could be reduced through at-colony monitoring. Strategic seabird satellite tagging could help target monitoring efforts to colonies known to use the nGoM, and continued vessel-based observations could improve habitat characterization. As offshore energy development in the nGoM continues, managers and researchers could use these vulnerability ranks to identify information gaps to prioritize research and focal species.

High levels of stress among occupational therapy graduate students have led to the adoption of unhealthy coping habits such as poor nutrition, little exercise, and disrupted sleep. In response, many institutions have explored programming and even curricular changes to support student well-being. However, very few are built upon a strong theoretical foundation to address holistic well-being. Therefore, this paper describes how logic modeling was used to develop a student well-being program based on Facilitating Learning and Occupational Well-Being Using Research-Based Initiatives for Student Health (FLOURISH), a theoretical approach rooted in the Person-Environment-Occupation Performance Model. A well-being program delivered via a virtual community of practice for entry-level students at a Midwestern occupational therapy program was created to decrease stress and enhance overall well-being for the performance of learning. The program consisted of eight 50-minute sessions that met once per week and included topics of physical, mental, sociocultural, environmental, and occupational well-being. The student well-being program is one viable option that shows promise to empower students with a theoretical approach to address personal and professional well-being, which has the potential to translate into professional practice. In this article, we describe the well-being program and the theoretical approach in detail and illustrate how it can be used to improve occupational therapy student well-being.

Background: Fusobacterium bacteria are fastidious commensals in the human oropharyngeal microbiome. As pathogens, Fusobacterium are associated with diverse infectious and inflammatory conditions, including Lemierre's syndrome, colorectal cancer, and inflammatory bowel disease. Portal and mesenteric thromboses associated with Fusobacterium are case-reportable; due to the rarity of these reports, the full spectrum of presentations and outcomes remains unknown. Case presentation: A 71-year-old man presented with two weeks of abdominal pain and night sweats. He was found to have extensive portal and mesenteric venous thromboses and pancolitis. Initial workup for hypercoagulable risk factors was negative; after discharge, blood cultures became positive for Fusobacterium nucleatum. The patient was treated with antibiotics and anticoagulation with complete resolution of symptoms, thromboses, and colitis. Conclusions: This report demonstrates the protean nature of Fusobacterium-associated disease, which in this patient was portal and mesenteric venous thromboses without oropharyngeal disease. We discuss the modes of transmission, mechanisms of infection, and what remains unknown about the causes and consequences of Fusobacterium-associated disease. This report also demonstrates that cases with atypical abdominal thromboses, despite a negative comprehensive workup, deserve a high suspicion for other causal factors that are not part of standard diagnostic evaluation.

The study objectives were to determine whether ovarian morphology can distinguish between women with regular menstrual cycles, normo-androgenic anovulation (NA-Anov), and PCOS and whether body mass index (BMI)-specific thresholds improved diagnostic potential. Women with PCOS (biochemical and/or clinical hyperandrogenism and irregular cycles; N = 66), NA-Anov (irregular cycles without clinical and/or biochemical hyperandrogenism; N = 64), or regular cycles (controls; cycles every 21–35 days in the absence of clinical or biochemical hyperandrogenism; N = 51) were evaluated. Participants underwent a reproductive history, physical exam, transvaginal ultrasound, and a fasting blood sample. Linear regression analyses were used to assess the impact of BMI on ovarian morphology across groups. The diagnostic performance of ovarian morphology for anovulatory conditions, and by BMI (lean: 2; overweight: ≥25 kg/m2), was tested using Receiver Operating Characteristic (ROC) curves. Follicle number per ovary (FNPO) and ovarian volume (OV), but not follicle number per cross-section (FNPS), increased across controls, NA-Anov, and PCOS. Overall, FNPO had the best diagnostic performance for PCOS versus controls (AUCROC = 0.815) and NA-Anov and controls (AUCROC = 0.704), and OV to differentiate between PCOS and NA-Anov (AUCROC = 0.698). In lean women, FNPO best differentiated between PCOS and controls (AUCROC = 0.843) and PCOS versus NA-Anov (AUCROC = 0.710). FNPS better distinguished between NA-Anov and controls (AUCROC = 0.687), although diagnostic performance was lower than when thresholds were generated using all participants. In women with overweight and obesity, OV persisted as the best diagnostic feature across all analyses (PCOS versus control, AUCROC = 0.885; PCOS versus NA-Anov, AUCROC = 0.673; NA-Anov versus controls, AUCROC = 0.754). Ovarian morphology holds diagnostic potential to distinguish between NA-Anov and PCOS, with marginal differences in diagnostic potential when participants were stratified by BMI suggesting that follicle number may provide better diagnostic performance in lean women and ovarian size in those with overweight.

Thrombocytopenia is common in patients with advanced liver disease. These patients frequently require invasive diagnostic or therapeutic procedures in the setting of thrombocytopenia. A common platelet goal before such procedures is ≥50,000/μL, but target levels vary by provider and the procedure. Platelet transfusion has disadvantages, including safety and cost. No other short‐term options for ameliorating thrombocytopenia before procedures were available until the thrombopoietin receptor agonists were recently approved. Avatrombopag and lusutrombopag can be used in certain patients with thrombocytopenia due to advanced liver disease undergoing elective invasive procedures; these new agents are highly effective in carefully selected patients, and real world data of safety and efficacy are awaited.

In the United States, single smokeless tobacco use continues to increase in conjunction with the dual use of smokeless tobacco and other nicotine products. Problematically, much of the tobacco prevention literature and funding inundates tobacco users with smoking tobacco information while neglecting to provide them any information about smokeless tobacco. Meanwhile, American tobacco companies continually market new and dissolvable tobacco products targeted at non-smokers. New data suggests that smokeless tobacco use is, also, increasing in West Virginia and, in order to address this increased use, the West Virginia Extension Service recently partnered with the Division of Tobacco Prevention in the West Virginia Department of Health and Human Resources to develop a comprehensive spit tobacco curriculum for West Virginia students between third and sixth grade. This article details the development and assessment of the spit tobacco prevention curriculum and the resulting report from the initial pilot of the program. The curriculum was piloted across six counties with the participation of schools, after-school programs and 4-H clubs. After implementation, survey results demonstrate that youth have increased awareness of the health effects of smokeless tobacco. Throughout the article, we explore West Virginia's Cooperative Extension Service's response to this emerging public health issue and release a call to action for the National Cooperative Extension Services to join us in spit tobacco prevention.

Human behaviour will continue to play an important role as the world grapples with public health threats. In this paper, we draw from the emerging evidence on behaviour adoption during diverse public health emergencies to develop a framework that contextualises behaviour adoption vis-à-vis a combination of top-down, intermediary and bottom-up approaches. Using the COVID-19 pandemic as a case study, we operationalise the contextual framework to demonstrate how these three approaches differ in terms of their implementation, underlying drivers of action, enforcement, reach and uptake. We illustrate how blended strategies that include all three approaches can help accelerate and sustain protective behaviours that will remain important even when safe and effective vaccines become more widely available. As the world grapples with the COVID-19 pandemic and prepares to respond to (re)emerging public health threats, our contextual framework can inform the design, implementation, tracking and evaluation of comprehensive public health and social measures during health emergencies.

Because dyspnoea is seldom experienced by healthy people, it can be hard for clinicians and researchers to comprehend the patient’s experience. We collected patients’ descriptions of dyspnoea in their own words during a parent study in which 156 hospitalised patients completed a quantitative multidimensional dyspnoea questionnaire. These volunteered comments describe the severity and wide range of experiences associated with dyspnoea and its impacts on a patients’ life. They provide insights not conveyed by structured rating scales. We organised these comments into the most prominent themes, which included sensory experiences, emotional responses, self-blame and precipitating events. Patients often mentioned air hunger (‘Not being able to get air is the worst thing that could ever happen to you.’), anxiety, and fear (‘Scared. I thought the world was going to end, like in a box.’). Their value in patient care is suggested by one subject’s comment: ‘They should have doctors experience these symptoms, especially dyspnoea, so they understand what patients are going through.’ Patients’ own words can help to bridge this gap of understanding.

The authors outline an innovative certificate program that promotes the Multicultural and Social Justice Counseling Competencies (MSJCC; Ratts, Singh, Massar-McMillan, Butler, & McCullough, 2015) and how counselor education programs can commit to a social justice approach. In addition, the authors provide a detailed summary of the certificate program that requires counselors-in-training to move beyond a multicultural understanding of diverse cultural worldviews so that they commit to becoming social change agents and take action on issues of equality and justice. Limitations and implications for counselor educators are presented.

Abstract Background Although breastfeeding duration in New Zealand’s indigenous Māori is shorter than in non-Māori, we know little about barriers or motivators of breastfeeding in this community. The aim of this analysis was to identify predictors for extended duration of breastfeeding amongst participants drawn from predominantly Māori communities in regional Hawke’s Bay. Methods Mother/baby dyads were recruited from two midwifery practices serving predominantly Māori women in mostly deprived areas, for a randomised controlled trial comparing the risks and benefits of an indigenous sleeping device (wahakura) and a bassinet. Questionnaires were administered at baseline (pregnancy) and at one, three and six months postnatal. Several questions relating to breastfeeding and factors associated with breastfeeding were included. The data from both groups were pooled to examine predictors of breastfeeding duration. Results Māori comprised 70.5% of the 197 participants recruited. The median time infants were fully breastfed was eight weeks and Māori women were more likely to breastfeed for a shorter duration than New Zealand European women with an odds-ratio (OR) of 0.45 (95% CI 0.24, 0.85). The key predictors for extended duration of breastfeeding were the strong support of the mother’s partner (OR = 3.64, 95% CI 1.76, 7.55) or her mother for breastfeeding (OR = 2.47, 95% CI 1.27, 4.82), longer intended duration of maternal breastfeeding (OR = 1.02, 95% CI 1.00, 1.03) and being an older mother (OR = 1.07, 95% CI 1.02, 1.12). The key predictors for shorter duration of breastfeeding were pacifier use (OR = 0.28, 95% CI 0.17, 0.46), daily cigarette smoking (OR = 0.51, 95% CI 0.37, 0.69), alcohol use (OR = 0.54, 95% CI 0.31, 0.93) and living in a more deprived area (OR 0.40, 95% CI 0.22, 0.72). Conclusions Breastfeeding duration in this group of mainly Māori women was shorter than the national average. Increasing the duration of breastfeeding by these mothers could be further facilitated by ante and postnatal education involving their own mothers and their partners in the support of breastfeeding and by addressing pacifier use, smoking and alcohol use.

Abstract Background Environmental cleanliness is one of the contributing factors for surgical site infections in the operating rooms (ORs). To decrease environmental contamination, pulsed xenon ultraviolet (PX-UV), an easy and safe no-touch disinfection system, is employed in several hospital environments. The positive effect of this technology on environmental decontamination has been observed in patient rooms and ORs during the end-of-day cleaning but so far, no study explored its feasibility between surgical cases in the OR. Methods In this study, 5 high-touch surfaces in 30 ORs were sampled after manual cleaning and after PX-UV intervention mimicking between-case cleaning to avoid the disruption of the ORs’ normal flow. The efficacy of a 1-min, 2-min, and 8-min cycle were tested by measuring the surfaces’ contaminants by quantitative cultures using Tryptic Soy Agar contact plates. Results We showed that combining standard between-case manual cleaning of surfaces with a 2-min cycle of disinfection using a portable xenon pulsed ultraviolet light germicidal device eliminated at least 70% more bacterial load after manual cleaning. Conclusions This study showed the proof of efficacy of a 2-min cycle of PX-UV in ORs in eliminating bacterial contaminants. This method will allow a short time for room turnover and a potential reduction of pathogen transmission to patients and possibly surgical site infections.

A substantial number of health-professional graduate students do not follow the national recommendation of obtaining at least seven hours of sleep per day. Decreased sleep duration and quality are strongly associated with daytime sleepiness and dysfunction, academic burnout, low academic performance, and mental health symptoms and disorders. However, limited research exists on sleep health among occupational therapy (OT) graduate students. Thus, the purpose of this study was to explore OT graduate student perspectives on sleep and to measure their sleep duration, quality, and practices to inform sleep promotion strategies for increased student well-being. A mixed-method study with a cross-sectional design was conducted. Occupational therapy graduate student participants engaged in a focus group and completed the Sleep Practices and Attitudes Questionnaire (SPAQ) along with a survey of demographic characteristics. Nineteen participants completed all aspects of the study. Participants slept an average of 6.75 hours per weekday night and rated their sleep quality an average of 3.47 out of 5 on a Likert scale (1: restless; 5: restful). The majority of participants (68.4%; n=13) reported feeling unrefreshed upon waking, and 78.9% (n=15) reported tiredness during the day. Three major themes emerged from the focus group data: 1) sleep prioritization and practice, 2) sleep knowledge versus action, and 3) occupational balance. This study is one of the first to assess sleep health among OT graduate students. Findings contribute to sleep health literature and may guide programming in sleep health promotion and graduate student well-being.

Focused thoracic ultrasound has become essential in the guidance and direction of pleural interventions to reduce unwanted complications and as a result now forms a crucial component of physician training. Current training standards along with assessment methods vary widely, and are often not robust enough to ensure adequate competence. This review assesses the current state of training and assessment of thoracic ultrasound competence in various settings, allowing comparison with alternative competency based programmes. Future directions for training and assessment of thoracic ultrasound competence are discussed.

Fetal macrosomia is associated with a number of health complications for both mother and infant in the immediate, short, and long-term. Maternal obesity and excessive gestational weight gain (GWG) have long been associated with fetal macrosomia, however the impact of maternal lifestyle factors such as dietary intake and energy balance, in combination with the timing and composition of weight gain, have been less studied. It is also clear that although maternal obesity and excessive GWG increase the risk of fetal macrosomia independently, the risk is magnified with the presence of both risk factors, suggesting that interventions to control GWG may be particularly important for obese women. Association studies examining the relationship between fetal nutrient availability, epigenetic modifications, and infant anthropometrics are also required. This review provides an overview of the current evidence examining the role of maternal lifestyle factors on the prevalence of fetal macrosomia and identifies areas where further research is required in order to inform the design of appropriate intervention strategies.

Urinary continence can be achieved in up to 90% of patients with bladder exstrophy. However, select patients remain incontinent despite modern reconstruction. Repeat operations for continence combined with the congenital pelvic abnormalities of exstrophy put patients at risk for urinary fistula formation. We report the use of a rectus muscle flap in the repair of two concomitant vesicocutaneous and urethrocutaneous fistulae in a patient with classic bladder exstrophy.

During 2018, four free-ranging conures, from a naturalized flock in San Francisco, presented with a characteristic set of neurologic signs that had been reported in other individuals from this flock. The cause of morbidity or mortality in historic cases has not been identified. From these four subjects, fresh feces were collected during their initial days of hospitalization and submitted to the University of Georgia Infectious Diseases Laboratory and Center for Applied Isotope Studies for bromethalin and desmethyl-bromethalin quantitation. Using High Performance Liquid Chromatography, the laboratory detected bromethalin, a non-anticoagulant, single-dose rodenticide, in fecal samples from three subjects; half of these samples were also positive for desmethyl-bromethalin, bromethalin's active metabolite. In three subjects that died, the UGA laboratory screened brain and liver samples and found bromethalin in all samples; desmethyl-bromethalin was detected in all but one brain sample, which was below the detection limit. Our findings suggest the conures are more resistant to bromethalin than are other species in which bromethalin has been studied, and/or that the conures may be ingesting the toxin at a sublethal dose. More data is needed to better assess the long-term effects of bromethalin on animals exposed at the subacute/chronic levels, and also to better understand the compartmentalization of bromethalin and desmethyl-bromethalin in a wider variety of species.

Objectives: Intravenous fluid (IV) therapy is an important component of care for many hospital patients, especially in perioperative and acute care settings. However, errors in fluid composition and dosing can be life-threatening. To achieve competent professional performance, i.e., accurate and fluent, it is vitally important that medical students receive effective training in IV fluid therapy. Methods: In this study, we explored how Precision Teaching (PT), a behaviour analytic teaching method, can enhance outcomes of usual medical education techniques. A total of 178 third-year medical students participated in the study during the IV fluid therapy training week. All students completed a multiple-choice test pre- and post-training. In addition to standard IV fluid therapy teaching, the experimental intervention group (n=83 students) used SAFMEDS (Say All Fast MinuteEvery Day Shuffled) cards approximately 3-5 times per day for 5 days. The other 95 students (control group) received teaching as usual, but did not undergo the additional training. Results: Results show that the SAFMEDS boosted performance of the intervention group on the MCQ by 20 percentage points when compared to the control group. Fluency (accuracy and speed) of performance on SAFMED trials increased markedly during the intervention week and there was evidence that weaker students benefitted in particular. Conclusions: Implications for medical education are outlined.

This case study examines new literacy opportunities and practices of 28 Latino/a children from grades one to seven in a South Texas colonia, or unincorporated area. Data sources were 24-hour literacy logs, two rounds of interviews, and participant observations. The children reported limited school work related to digital literacies; the technology they accessed outside of school focused on entertainment, communication with friends, and mostly non-challenging video games. We discuss participants’ ingenious ways of circumventing any lack of access, their underlying social practices of community sharing, and Thirdspace possibilities of the tutorial center that respondents attended.

Kathy M Hageman1, Etienne Karita2, Kayitesi Kayitenkore2, Roger Bayingana2, Ariane van der Straten3, Rob Stephenson4, Martha Conkling5, Amanda Tichacek1, Lawrence Mwananyanda5, William Kilembe5, Alan Haworth6, Elwyn Chomba6, Susan A Allen11Rwanda Zambia HIV Research Group, Emory University, Atlanta, Georgia, USA; 2Projet San Francisco, Kigali, Rwanda; 3Women’s Global Health Imperative, RTI International, San Francisco, USA; 4Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; 5Zambia Emory HIV Research Project, Lusaka, Zambia; 6University Teaching Hospital, Lusaka, Zambia Objective: To compare responses to a sexual behavioral survey of spouses in cohabiting heterosexual relationships in Kigali, Rwanda.Design: Cross-sectional survey.Methods: Husbands and wives in 779 cohabiting couples were interviewed separately with parallel questionnaires. Participants were recruited from a three-year old cohort of 1458 antenatal clinic attendees enrolled in a prospective study in 1988. Analyses compared responses at the gender- and couple-level for agreement and disagreement.Results: Couples were in disagreement more than agreement. Women reported occasionally refusing sex, suggesting condom use, and believing married men were unfaithful. Men reported being in a faithful relationship, greater condom use, and being understanding when his wife refused sex. Agreement included relationship characteristics, safety of condoms, and whether condoms had ever been used in the relationship. Disagreement included the preferred timing of next pregnancy, desire for more children, and whether a birth control method was currently used and type of method.Conclusions: Rwandan husbands and wives differed in sexual behavior and reproductiverelated topics. Couple-level reporting provides the most reliable measure for relationship aspects as couples’ agreement cannot be assumed among cohabiting partnerships. Furthermore, HIV prevention programs for couples should incorporate communication skills to encourage couple agreement of HIV-related issues.Keywords: HIV, couples, counseling and testing, agreement and disagreement, sexual behavior, condom use, and pregnancy

The distribution of α6/α3 integrin in adhesion complexes at the basal membrane in human normal and cancer prostate glands was analyzed in 135 biopsies from 61 patients. The levels of the polarized α6/α3 integrin expression at the basal membrane of prostate tumor glands were determined by quantitative immunohistochemistry. The α6/α3 integrin expression was compared with Gleason sum score, pathological stage, and preoperative serum prostate-specific antigen (PSA). The associations were assessed by statistical methods. Eighty percent of the tumors expressed the α6 or α3 integrin and 20% was integrin-negative. Gleason sum score, but not serum PSA, was associated with the integrin expression. Low Gleason sum score correlated with increased integrin expression, high Gleason sum score with low and negative integrin expression. Three prostate tumor phenotypes were distinguished based on differential integrin expression. Type I coexpressed both α6 and α3 subunits, type II exclusively expressed a6 integrin, and type III expressed α3 integrin only. Fifteen cases were further examined for the codistribution of vinculin, paxillin, and CD 151 on frozen serial sections using confocal laser scanning microscopy. The α6/α3 integrins, CD151, paxillin, and vinculin were present within normal glands. In prostate carcinoma, α6 integrin was colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I, the α6 subunit did not colocalize with the α3 subunit indicating the existence of two different adhesion complexes. Human prostate tumors display on their cell surface the α6β1 and/or α3β1 integrins. Three tumor phenotypes associated with two different adhesion complexes were identified, suggesting a reorganization of cell adhesion structures in prostate cancer.

Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeated cocaine administration. In the present study, we investigated synaptic plasticity induced by exogenous DA and its dependence on mGluR signaling and a potential role for phospholipase D (PLD) as a downstream element linked to mGluR and DR signaling. Utilizing a modified conditioned place preference (CPP) paradigm as a functional behavioral measure, we studied the neurophysiological effects after two-weeks to the last cocaine conditioning. We recorded, electrophysiologically, a DR-induced synaptic potentiation in the basolateral to lateral capsula central amygdala (BLA-lcCeA) synaptic pathway that was blocked by antagonists of group I mGluRs, particularly, the PLD-linked mGluR. In addition, we observed 2-2.5 fold increase in PLD expression and 3.7-fold increase in basal PLD enzyme activity. The enhanced PLD activity could be further stimulated (9.3 fold) by a DA D1-like (D1/5R) receptor agonist, and decreased to control levels by mGluR1 and PLD-linked mGluR antagonists. Diminished CPP was observed by infusion of a PLD-linked mGluR antagonist, PCCG-13, in the amygdala 15 minutes prior to testing, two weeks after the last cocaine injection. These results imply a functional interaction between D1/5Rs, group I mGluRs via PLD in the amygdala synaptic plasticity associated with cocaine-cues.

In this work, we compare two methods for evaluating and quantifying pulmonary airspace enlargement in a mouse model of chronic cigarette smoke exposure. Standard stereological sample preparation, sectioning, and imaging of mouse lung tissues were performed for semi-automated acquisition of mean linear intercept (L(m)) data. After completion of the L(m) measurements, D(2), a metric of airspace enlargement, was measured in a blinded manner on the same lung images using a fully automated technique developed in-house. An analysis of variance (ANOVA) shows that although L(m) was able to separate the smoke-exposed and control groups with statistical significance (p = 0.034), D(2) was better able to differentiate the groups (p

Background Refractory meibomian gland dysfunction (MGD) is a prevalent condition characterized by chronic functional abnormalities of the meibomian glands, leading to altered tear film and ocular discomfort despite medical treatments. Traditional management strategies include various single-modality treatments, although there is growing interest in the efficacy of combined therapies. Aim The aim of this study was to evaluate the efficacy of regimens used individually and in combination for the treatment of refractory MGD. Methods This retrospective study involved pre- and posttreatment evaluations of the ocular surface and symptoms in patients with refractory MGD. Treatments included meibomian gland probing (MGP), intense pulsed light (IPL) therapy, thermal pulsation (LipiFlow), IPL + MGP, and MGP + LipiFlow. Results In total, 325 eyes of 241 patients with refractory MGD were assessed. The MGP group showed significant improvements in the ocular surface disease index (OSDI), tear meniscus height (TMH), corneal and conjunctival staining, lid wiper epitheliopathy (LWE), and meibomian gland expression (MGX) score. The IPL group showed significant improvements in OSDI, TMH, redness, conjunctival staining, and MGX score. IPL + MGP resulted in significant improvements in corneal and conjunctival staining, LWE, and MGX score, while LipiFlow significantly improved conjunctival staining, LWE, and MGX score. No significant improvements were observed in the MGP + LipiFlow group. Conclusion IPL or MGP alone could alleviate the signs and symptoms of refractory MGD, while LipiFlow and IPL + MGP could improve the ocular surface parameters. However, no significant improvements were observed with MGP + LipiFlow. These findings provide a valuable guide for ophthalmologists for the selection of effective treatment modalities for refractory MGD, suggesting a potential advantage of combined IPL + MGP to maximize therapeutic benefits.

Abstract Background A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support. This single-arm, non-randomised feasibility study explored the feasibility and acceptability of a Comprehensive REsilience-building psychoSocial intervenTion (CREST) for people with dementia, their caregivers, General Practitioners (GPs), and the public. Methods Nine people with dementia and their primary caregivers living in the community (n = 9 dyads) completed the CREST intervention which had three components (cognitive stimulation therapy [CST], physical exercise, and dementia education). Quantitative secondary outcomes were assessed at baseline and following the 15-week intervention; qualitative interviews were conducted during and post-intervention. All study components were assessed against pre-defined criteria, to determine the feasibility of conducting a future definitive trial. Results Recruitment of people with dementia and their caregiver was a significant challenge and led to considerable delays to the onset and conduct of the intervention. Only 13% of eligible GP practices agreed to assist in recruitment and achieved a 6% enrolment rate; a community-based recruitment strategy proved more effective, yielding a 29% enrolment rate. However, once recruited, participants maintained high attendance and adherence to the content of each component with average adherence rates of 98% for CST, exercise sessions and caregiver education. Adherence to secondary exercise measures was lower, with home exercise diary completion at 37% and Fitbit wear adherence at 80% during the day and 67% at night. The people with dementia felt their concentration and fitness had improved over the 15-week intervention and particularly enjoyed the social aspects (e.g. group classes, exercising with partners from the community). Caregivers felt they had better knowledge and understanding following their education component and reported that the social aspects (interacting and sharing experiences with each other) were important. Overall, participants reported that the three components of the intervention were feasible and acceptable. In addition, the quantitative measures and health economic tools employed were feasible. However, the secondary elements of the exercise component (recording home exercise diaries and Fitbit use) were not considered feasible. Overall, pre-defined criteria for progression to a definitive intervention were fulfilled in terms of acceptability, retention and fidelity but not recruitment. Conclusion While overall, the CREST intervention was feasible and acceptable to participants, significant difficulties with recruitment of people with dementia and their caregiver through GP practices impacted the viability of delivering the intervention. Recruitment through community-based groups proved a more feasible option and further work is needed to overcome barriers to recruiting this cohort before a larger-scale trial can be conducted. Trial registration ISRCTN25294519.

Abstract Background A novel Complex REsilience-building psychoSocial intervenTion (CREST) targeted at people with dementia, their informal carers, general practitioners and the wider community with the aim of increasing resilience and strengthening the personal attributes or external assets of people with dementia living at home, in the community, was developed. It included three components: cognitive stimulation therapy (CST), physical exercise and dementia education. A non-randomised feasibility study was conducted of the CREST intervention, the aim of which was to inform the design of a future randomised controlled trial. This article presents the findings from the qualitative component of the CREST intervention feasibility study, describing the experience of the people with dementia and their caregivers who participated and the volunteer older adults who supported the intervention. Methods A descriptive qualitative research approach using semi-structured interviews was undertaken. Key stakeholders (people with dementia (n = 9), their caregivers (n = 9) and the volunteer older adults from the physical exercise component (n = 9)) were interviewed about the intervention and the perceived impact of their participation. Results The social aspect of the CREST intervention proved to be important for all three groups. Attendance remained high throughout the intervention. The people with dementia spoke positively about their participation in the CST and exercise components of the CREST intervention. The caregivers liked receiving coping strategies focused on how to communicate better with the person they cared for and how to better manage their own self-care and they liked the group element of the programme. The volunteer older adults supported the people with dementia in taking part in the exercise component, motivating them to do the exercises and helping with social interaction within the group. The volunteers gained exposure to the illness and as a result understood more about dementia and felt better equipped to communicate and deal with people with dementia. Conclusion Participation in the CREST intervention produced a positive impact on all three groups. The social element of the intervention was noted by everybody and was regarded as being beneficial. Qualitative insights emphasised the value of embedding qualitative research within feasibility studies to inform future intervention design. Further research should focus on conducting a full-scale randomised controlled trial to evaluate CREST’s effectiveness and explore its application to individuals with more advanced dementia. Trial registration ISRCTN25294519.

Numerous studies have established that prebiotic ingredients in foods and dietary supplements may play a role in supporting human health. Over the three decades that have passed since prebiotics were first defined as a concept, research has revealed a complex universe of prebiotic-induced changes to the human microbiota. There are strong indications of a direct link between these prebiotic-induced changes and specific health benefits. However, at the present time, the EU has not permitted use of the term ‘prebiotic’ in connection with an approved health claim. This paper is the outcome of a workshop organized on the 25th October 2023 by the European branch of the International Life Science Institute (ILSI). It provides an overview of the regulatory requirements for authorized health claims in the EU, key areas of prebiotic research, and findings to date in relation to prebiotics and digestive, immune, metabolic and cognitive health. Research gaps and documentation challenges are then explored and a roadmap proposed for achieving authorization of ‘prebiotic’ in the wording of future EU health claims.

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

ABSTRACT Measuring the outcome of practical interventions and actions helps to inform conservation management objectives and assess progress towards objectives and targets. Measuring success also informs future management by identifying actions that are effective and those that are not. Scrub vegetation is an important habitat type in terrestrial ecosystems, providing important shelter and food resources for biodiversity and livestock. Much of practical land management in the UK involves the monitoring and management of scrub, and current drone‐based methods of scrub collection requires expensive equipment or complex methods. A 2021 paper determined a cheap and simple way to determine scrub levels, and this could potentially be used to map temporal changes, as well as identify directional change in scrub. This study looks at whether the method outlined in the 2021 study could be used to measure temporal and directional changes in scrub cover on two nature reserves in the UK: Daneway Banks in Gloucestershire and Flat Holm Island in the Severn Estuary. Scrub levels at Daneway Banks increased from 14.63% in 2015 to 16.52% in 2017, before decreasing to 14.89% in 2021 due to managed cutting and clearing. Scrub cover at Flatholm Island decreased from 10.18% in 2019 to 8.71% in 2021. The exact locations of scrub growth and loss for each site was also calculated and mapped. This approach was found to be a viable way of measuring temporal and directional change in scrub levels. The data can also be used to reframe changes in scrub levels as a shift towards vegetation succession or reduction, to better visualise how changes in scrub levels affect overall site management goals, and is a cheaper, more accessible alternative to current methods of measuring temporal vegetation changes.

Objectives The purpose of this study is to describe and evaluate, in a real-life context, the support and communicate with families (SCF) team’s contribution to maintaining communication and supporting relatives when patients are at the end of their lives by mobilising the points of view of SCF team members, healthcare professionals, managers and the relatives themselves.Design An in-depth mixed-method case study (quantitative and qualitative). Individual interviews were conducted with members of the SCF team to assess the activities and areas for improvement and with co-managers of active COVID-19 units. Healthcare professionals and managers completed a questionnaire to assess the contribution made by the SCF team. Hospitalised patients’ relatives completed a questionnaire on their experience with the SCF team.Setting The study was conducted in a university teaching hospital in the province of Québec, Canada.Participants Members of the SCF team, healthcare professionals, managers and relatives of hospitalised patients.Results Between April and July 2020, 131 telephone communications with families and healthcare professionals, 43 support sessions for relatives of end-of-life patients and 35 therapeutic humanitarian visits were carried out by members of the SCF team. Team members felt that they had played an active role in humanising care. Fully 83.1% of the healthcare professionals and managers reported that the SCF team’s work had met the relatives’ needs, while 15.1% believed that the SCF team should be maintained after the pandemic. Fully 95% of the relatives appreciated receiving the telephone calls and visits, while 82% felt that the visits had positive effects on hospitalised patients.Conclusion The COVID-19 pandemic forced the introduction of a social innovation involving support for and communication with families. The intention of this innovation was to support the complexity of highly emotional situations experienced by families during the COVID-19 pandemic.

Objective: Despite the popularity of nicotine gum in Thailand, population pharmacokinetics of nicotine gum in the Thai population has not been investigated. This study aimed to develop a population pharmacokinetic (POPPK) model of nicotine and to quantify the effects of genetic and non-genetic factors to nicotine pharmacokinetics. Materials and Methods: Secondary data collected from a previous clinical trial assessing cytochrome P450 2A6 (CYP2A6) genotypes in Thai smokers was investigated. Eighteen participants who had received a single dose of 2 mg nicotine gum were included. Blood samples were collected before, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4.5 and 6 hours after nicotine administration. POPPK analysis was performed using nonlinear mixed effect modelling. Results: One-compartment with 1st order elimination and absorption with 6-transit compartments best described the data. CYP2A6 enzyme activity was a significant covariate on the nicotine clearance. Apparent elimination clearance (CL/F) for a person with 100% CYP2A6 activity was 266.0 L/h. CL/F would be 36.0 L/h in a subject with 0% CYP2A6 activity. However, the impact of non-genetic factors (monthly alcohol consumption, Fagerstrom Test for Nicotine Dependence score and the number of cigarettes per day) on pharmacokinetics of nicotine were not found. Conclusion: This first report on population pharmacokinetics of nicotine gum in Thai smokers provided the pharmacokinetic model and quantified CL/F for smokers with different CYP2A6 genotypes. A markedly lower exposure to nicotine in the Thai population compared to others highlights the need for more studies to ensure the efficacy of nicotine gum in the Thai population.

Abstract Background Half of mental health problems are established by the age of 14 years and 75% by 24 years. Early intervention and prevention of mental ill health are therefore vitally important. However, increased demand over recent years has meant that access to child mental health services is often restricted to those in severest need. Watch Me Play! (WMP) is an early intervention designed to support caregiver attunement and attention to the child to promote social-emotional well-being and thereby mental health resilience. Originally developed in the context of a local authority mental health service for children in care, it is now also delivered online as a low intensity, scalable, preventative intervention. Although WMP shows promise and is already used in some services, we do not yet know whether it is effective. Methods A non-randomised single group feasibility study with embedded process evaluation. We propose to recruit up to 40 parents/carers of children aged 0–8 years who have been referred to early years and children’s services in the UK. WMP involves a parent watching the child play and talking to their child about their play (or for babies, observing and following signals) for up to 20 min per session. Some sessions are facilitated by a trained practitioner who provides prompts where necessary, gives feedback, and discusses the child’s play with the caregiver. Services will offer five facilitated sessions, and parents will be asked to do at least 10 additional sessions on their own with their child in a 5-week period. Feasibility outcomes examined are as follows: (i) recruitment, (ii) retention, (iii) adherence, (iv) fidelity of delivery, (v) barriers and facilitators of participation, (vi) intervention acceptability, (vii) description of usual care, and (viii) data collection procedures. Intervention mechanisms will be examined through qualitative interview data. Economic evaluation will be conducted estimating cost of the intervention and cost of service use for child and parents/carers quality-adjusted life years. Discussion This study will address feasibility questions associated with progression to a future randomised trial of WMP. Trial registration ISRCTN13644899 . Registered on 14th April 2023.

Abstract The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8+ T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8+ T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.

SignificanceMany commercially available near-infrared (NIR) fluorescence imaging systems lack algorithms for real-time quantifiable fluorescence data. Creation of a workflow for clinical assessment and post hoc analysis may provide clinical researchers with a method for intraoperative fluorescence quantification to improve objective outcome measures.AimScoring systems and verified image analysis are employed to determine the amount and intensity of fluorescence within surgical specimens both intra and postoperatively.ApproachLymph nodes from canine cancer patients were obtained during lymph node extirpation following peritumoral injection of indocyanine green (ICG). First, a semi-quantitative assessment of surface fluorescence was evaluated. Images obtained with a NIR exoscope were analysed to determine fluorescence thresholds and measure fluorescence amount and intensity.ResultsPost hoc fluorescence quantification (threshold of Hue = 165–180, Intensity = 30–255) displayed strong agreement with semi-quantitative scoring (k = 0.9734, p

IntroductionThe enteric microbiome and its possible modulation to improve feed conversion or vaccine efficacy is gaining more attention in pigs. Weaning pigs from their dam, along with many routine procedures, is stressful. A better understanding of the impact of this process on the microbiome may be important for improving pig production. The objective of this study was to develop a weaner pig cannulation model, thus allowing ileum content collection from the same pig over time for 16S rRNA sequencing under different porcine reproductive and respiratory syndrome virus (PRRSV) infection statuses.MethodsA total of 15 3-week-old pigs underwent abdominal surgery and were fitted with an ileum cannula, with ileum contents collected over time. In this pilot study, treatment groups included a NEG-CONTROL group (no vaccination, no PRRSV challenge), a POS-CONTROL group (no vaccination, challenged with PRRSV), a VAC-PRRSV group (vaccinated, challenged with PRRSV), a VAC-PRO-PRRSV group (vaccinated, supplemented with a probiotic, challenged with PRRSV), and a VAC-ANTI-PRRSV group (vaccinated, administered an antibiotic, challenged with PRRSV). We assessed the microbiome over time and measured anti-PRRSV serum antibodies, PRRSV load in serum and nasal samples, and the severity of lung lesions.ResultsVaccination was protective against PRRSV challenge, irrespective of other treatments. All vaccinated pigs mounted an immune response to PRRSV within 1 week after vaccination. A discernible impact of treatment on the diversity, structure, and taxonomic abundance of the enteric microbiome among the groups was not observed. Instead, significant influences on the ileum microbiome were observed in relation to time and treatment.DiscussionThe cannulation model described in this pilot study has the potential to be useful in studying the impact of weaning, vaccination, disease challenge, and antimicrobial administration on the enteric microbiome and its impact on pig health and production. Remarkably, despite the cannulation procedures, all vaccinated pigs exhibited robust immune responses and remained protected against PRRSV challenge, as evidenced by the development of anti-PRRSV serum antibodies and viral shedding data.

This special issue of Oñati Socio-legal Series, titled Judging, Emotion and Emotion Work, is the result of presentations and discussions during an interdisciplinary workshop at the International Institute for the Sociology of Law (IISL) held in May 2018. This issue builds on the growing critique of the dispassionate ideal of judicial work, combining original theoretical insights with imaginative empirical analyses to extend the understanding of emotion in judging. Fifteen articles are presented in four themes: Theoretical, cultural and historical perspectives; Tensions of the dispassionate ideal; Social dynamics of emotion in judging; and Research methods, empirical insights and [changing] judicial practice. The international diversity of contributions recognises similarities and differences in the structure and organization of courts and the judiciary, and socio-cultural variations in emotional experience and expression.

Abstract Background Injuries, the leading cause of death in children 1–17 years old, are often preventable. Injury patterns are impacted by changes in the child’s environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. Methods This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children

Abstract Background Increasing numbers of family carers are providing informal care in community settings. This creates a number of challenges because family carers are at risk of poor physical and psychological health outcomes, with consequences both for themselves and those for whom they provide care. General Practitioners (GPs), who play a central role in community-based care, are ideally positioned to identify, assess, and signpost carers to supports. However, there is a significant gap in the literature in respect of appropriate guidance and resources to support them in this role. Methods A scoping review was undertaken to examine clinical guidelines and recommendations for GPs to support them in their role with family carers. This involved a multidisciplinary team, in line with Arksey & O’Malley’s framework, and entailed searches of ten peer-reviewed databases and grey literature between September-November 2020. Results The searches yielded a total of 4,651 English language papers, 35 of which met the criteria for inclusion after removing duplicates, screening titles and abstracts, and performing full-text readings. Ten papers focused on resources/guidelines for GPs, twenty were research papers, three were review papers, one was a framework of quality markers for carer support, and one was an editorial. Data synthesis indicated that nine (90%) of the guidelines included some elements relating to the identification, assessment, and/or signposting of carers. Key strategies for identifying carers suggest that a whole practice approach is optimal, incorporating a role for the GP, practice staff, and for the use of appropriate supporting documentation. Important knowledge gaps were highlighted in respect of appropriate clinical assessment and evidence-based signposting pathways. Conclusion Our review addresses a significant gap in the literature by providing an important synthesis of current available evidence on clinical guidelines for GPs in supporting family carers, including strategies for identification, options for assessment and potential referral/signposting routes. However, there is a need for greater transparency of the existing evidence base as well as much more research to evaluate the effectiveness and increase the routine utilisation, of clinical guidelines in primary care.

Abstract Ovarian cancers exhibit high rates of recurrence and poor treatment response. Preclinical models that recapitulate human disease are critical to develop new therapeutic approaches. Syngeneic mouse models allow for the generation of tumours comprising the full repertoire of non-malignant cell types but have expanded in number, varying in the cell type of origin, method for transformation, and ultimately, the properties of the tumours they produce. Here we have performed a comparative analysis of high-grade serous ovarian cancer models based on transcriptomic profiling of 22 cell line models, and intrabursal and intraperitoneal tumours from 12. Among cell lines, we identify distinct signalling activity, such as elevated inflammatory signalling in STOSE and OVE16 models, and MAPK/ERK signalling in ID8 and OVE4 models; metabolic differences, such as reduced glycolysis-associated expression in several engineered ID8 subclones; and relevant functional properties, including differences in EMT activation, PD-L1 and MHC class I expression, and predicted chemosensitivity. Among tumour samples, we observe increased variability and stromal content among intrabursal tumours. Finally, we predict differences in the microenvironment of ID8 models engineered with clinically relevant mutations. We anticipate that this work will serve as a valuable resource, providing new insight to help select models for specific experimental objectives.

Background: Wastewater is a major source of Antibiotic-Resistant Bacteria (ARB) and a hotspot for the exchange of Antibiotic-Resistant Genes (ARGs). The occurrence of Carbapenem-Resistant Bacteria (CRB) in wastewater samples is a major public health concern. Objectives: This study aimed to analyze Antibiotic resistance in bacteria from wastewater sources in Pakistan. Methods: We analyzed 32 bacterial isolates, including 18 Escherichia coli, 4 Klebsiella pneumoniae, and 10 other bacterial isolates using phenotypic antibiotic susceptibility assay and whole-genome sequencing. This study identified the ARGs, plasmid replicons, and integron genes cassettes in the sequenced isolates. One representative isolate was further sequenced using Illumina and Oxford nanopore sequencing technologies. Results: Our findings revealed high resistance to clinically important antibiotics: 91% of isolates were resistant to cefotaxime, 75% to ciprofloxacin, and 62.5% to imipenem, while 31% showed non-susceptibility to gentamicin. All E. coli isolates were resistant to cephalosporins, with 72% also resistant to carbapenems. Sequence analysis showed a diverse resistome, including carbapenamases (blaNDM-5, blaOXA-181), ESBLs (blaCTX-M-15, blaTEM), and AmpC-type β-lactamases (blaCMY). Key point mutations noticed in the isolates were pmrB_Y358N (colistin) and ftsI_N337NYRIN, ftsI_I336IKYRI (carbapenem). The E. coli isolates had 11 different STs, with ST410 predominating (28%). Notably, the E. coli phylogroup A isolate 45EC1, (ST10886) is reported for the first time from wastewater, carrying blaNDM-5, blaCMY-16, and pmrB_Y358N with class 1 integron gene cassette of dfrA12-aadA2-qacEΔ1 on a plasmid-borne contig. Other carbapenamase, blaNDM-1 and blaOXA-72, were detected in K. pneumoniae 22EB1 and Acinetobacter baumannii 51AC1, respectively. The integrons with the gene cassettes encoding antibiotic resistance, and the transport and bacterial mobilization protein, were identified in the sequenced isolates. Ten plasmid replicons were identified, with IncFIB prevalent in 53% of isolates. Combined Illumina and Oxford nanopore sequencing revealed blaNDM-5 on an IncFIA/IncFIC plasmid and is identical to those reported in the USA, Myanmar, and Tanzania. Conclusions: These findings highlight the environmental prevalence of high-risk and WHO-priority pathogens with clinically important ARGs, underscoring the need for a One Health approach to mitigate ARB isolates.

Abstract Background The prevalence of COPD continues to rise. To address the challenges to provide high quality COPD care in rural and northern communities, leaders in one rural and northern community in Western Canada sought to change the culture of COPD screening and care. Recognizing effective assessment, diagnosis, and treatment for patients with COPD are crucial to improve outcomes, a program was developed between 2012 and 2021 to enhance primary care for COPD patients. Methods A process evaluation was undertaken to assess program development, implementation, mechanisms of impact, and context of COPD program. Qualitative thematic analysis of stakeholder interviews (n = 11) and a document review (n = 60; ~ 500 pages) of key clinic documents was conducted. Results We describe five phases of the COPD program’s development (Survive; Reorganize and Stabilize; Assess and Respond; Build and Refine; and Sustain and Share), highlighting areas of innovation. Outreach and localizing resources improved access to the program. Acquiring secured physician compensation, capturing quality data, and improving patient and provider self-efficacy built the capacity of the system and stakeholders within it. Finally, relationships were forged through building an integrated facility, collaborative networking, and patient engagement. Key elements of program implementation included the resources (infrastructure, software, operational) required to ensure operation. Conclusion Team-based care and service integration enhanced care capacity and the health network. Focused use of infrastructure and resources supported the people in the care system. Upholding a shared value of relationship is critical to deliver robust and sustainable rural healthcare. Quality improvement requires investment in rural community healthcare resources.

Abstract Objective To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer. Methods An electronic database search of the Embase, MEDLINE and Web of Science from inception until July 7, 2023, was conducted to identify primary studies that investigated the effect of liposomal delivery of gene therapy on ovarian cancer outcomes. Retrieved studies were assessed against the eligibility criteria for inclusion. Results The search yielded 564 studies, of which 75 met the inclusion criteria. Four major types of liposomes were identified: cationic, neutral, polymer-coated, and ligand-targeted liposomes. The liposome with the most evidence involved cationic liposomes which are characterized by their positively charged phospholipids (n = 37, 49.3%). Similarly, those with neutrally charged phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine, were highly researched as well (n = 25, 33.3%). Eight areas of gene therapy research were identified, evaluating either target proteins/transcripts or molecular pathways: microRNAs, ephrin type-A receptor 2 (EphA2), interleukins, mitogen-activated protein kinase (MAPK), human-telomerase reverse transcriptase/E1A (hTERT/EA1), suicide gene, p53, and multidrug resistance mutation 1 (MDR1). Conclusion Liposomal delivery of gene therapy for ovarian cancer shows promise in many in vivo studies. Emerging polymer-coated and ligand-targeted liposomes have been gaining interest as they have been shown to have more stability and specificity. We found that gene therapy involving microRNAs was the most frequently studied. Overall, liposomal genetic therapy has been shown to reduce tumor size and weight and improve survivability. More research involving the delivery and targets of gene therapy for ovarian cancer may be a promising avenue to improve patient outcomes.

Abstract Background In studies of the general population and of military veterans, many primary care patients with hazardous drinking and PTSD and/or depression (abbreviated here as HD +) do not initiate or engage with alcohol-related care. To address this gap in care, we identified and will pilot test a promising evidence-based intervention, Connect To Care (C2C). C2C is a strengths-based approach, delivered by a Care Coach by telephone and/or video, with four components: (1) identifying and leveraging patient strengths to facilitate care initiation, (2) collaborative decision-making around a menu of care options, (3) identifying and resolving barriers to care, and (4) monitoring and facilitating progress toward care initiation by, for example, checking on barriers, identifying solutions, and revisiting care options. Methods/Design Aim 1 will involve adapting C2C for use in Veterans Affairs’ (VA) primary care. We will use an iterative process that includes focus groups and semi-structured interviews with key stakeholders (patients, primary care providers, and VA national policy leaders). In Aim 2, we will conduct a two-site, pilot randomized controlled trial to determine the feasibility of conducting a larger scale trial to test C2C’s effectiveness, ascertain the acceptability of C2C among primary care patients with HD + , and explore the efficacy of C2C to improve veteran patients’ initiation of and engagement in alcohol care, and their alcohol and mental health (PTSD, depression) outcomes, at 3-month follow-up. We will explore explanatory mechanisms by which C2C is effective. Discussion Study findings are likely to have implications for clinical practice to enhance current approaches to linking patients with HD + to alcohol care by applying a practical intervention such as C2C. The results may improve treatment outcomes for people with HD + by drawing on patients’ strengths to problem-solve barriers to care following a process of shared decision-making with a coach. In addition to possibly accelerating the translation of C2C into practice, study findings will also support additional research in terms of a planned effectiveness-implementation hybrid trial, adding to this study’s potential for high impact. Trial registration: ClinicalTrials.gov Identifier: NCT05023317.

The lack of a robust, widely accepted theory on corporate social responsibility has meant that business leaders are often unaware, or doubtful, about the presence of social responsibility across a wide spectrum of business practices in which it is manifested. Since undergraduate students on management-related degree programs are future business leaders, it is important to enquire into the knowledge they have on this subject. To this end, a sample was selected of students from universities in ten Spanish-speaking Latin American countries: Argentina, Bolivia, Chile, Colombia, Ecuador, Mexico, Nicaragua, Panama, Peru, Uruguay, and Venezuela. A structured questionnaire was used to measure their knowledge of 18 social responsibility practices representative of three dimensions of the concept: internal responsibility, responsibility towards external stakeholders of the value chain and responsibility towards the environment. It was found that there is a widespread lack of knowledge about the business practices that constitute social responsibility actions, that some practices are better known than others (the best known are those related to the environment while the least known are those related with the external stakeholders of the value chain), and that the extent of this knowledge depends on the country where the universities are located. In addition, it was found that the relationship between knowledge and country is not mediated by gender, age, work experience, degree program studied, or year of study. These results suggest that the teaching of social responsibility in Latin American universities does not place equal emphasis on all dimensions of the concept, and that this teaching differs from one country to another.

BackgroundLiver transplantation (LT) is indicated in patients with severe acute or chronic liver failure for which no other therapy is available. With the increasing number of LTs in recent years, liver centers worldwide must manage their patients according to their clinical situation and the expected waiting time for transplantation. The LT clinic at the Centre hospitalier de l’Université de Montréal (CHUM) is developing a new health care model across the entire continuum of pre-, peri-, and posttransplant care that features patient monitoring by an interdisciplinary team, including an accompanying patient; a digital platform to host a clinical plan; a learning program; and data collection from connected objects. ObjectiveThis study aims to (1) evaluate the outcomes following the implementation of a patient platform with connected devices and an accompanying patient, (2) identify implementation barriers and facilitators, (3) describe service outcomes in terms of health outcomes and the rates and nature of contact with the accompanying patient, (4) describe patient outcomes, and (5) assess the intervention’s cost-effectiveness. MethodsSix types of participants will be included in the study: (1) patients who received transplants and reached 1 year after transplantation before September 2023 (historical cohort or control group), (2) patients who will receive an LT between December 2023 and November 2024 (prospective cohort/intervention group), (3) relatives of those patients, (4) accompanying patients who have received an LT and are interested in supporting patients who will receive an LT, (5) health care professionals, and (6) decision makers. To describe the study sample and collect data to achieve all the objectives, a series of validated questionnaires, accompanying patient logbooks, transcripts of interviews and focus groups, and clinical indicators will be collected throughout the study. ResultsIn total, 5 (steering, education, clinical-technological, nurse prescription, and accompanying patient) working committees have been established for the study. Recruitment of patients is expected to start in November 2023. All questionnaires and technological platforms have been prepared, and the clinicians, stakeholders, and accompanying patient personnel have been recruited. ConclusionsThe implementation of this model in the trajectory of LT recipients at the CHUM may allow for better monitoring and health of patients undergoing transplantation, ultimately reducing the average length of hospital stay and promoting better use of medical resources. In the event of positive results, this model could be transposed to all transplant units at the CHUM and across Quebec (potentially affecting 888 patients per year) but could also be applied more widely to the monitoring of patients with other chronic diseases. The lessons learned from this project will be shared with decision makers and will serve as a model for other initiatives involving accompanying patients, connected objects, or digital platforms. International Registered Report Identifier (IRRID)PRR1-10.2196/54440

The lack of a robust, widely accepted theory on corporate social responsibility has meant that business leaders are often unaware, or doubtful, about the presence of social responsibility across a wide spectrum of business practices in which it is manifested. Since undergraduate students on management-related degree programs are future business leaders, it is important to enquire into the knowledge they have on this subject. To this end, a sample was selected of students from universities in ten Spanish-speaking Latin American countries: Argentina, Bolivia, Chile, Colombia, Ecuador, Mexico, Nicaragua, Panama, Peru, Uruguay, and Venezuela. A structured questionnaire was used to measure their knowledge of 18 social responsibility practices representative of three dimensions of the concept: internal responsibility, responsibility towards external stakeholders of the value chain and responsibility towards the environment. It was found that there is a widespread lack of knowledge about the business practices that constitute social responsibility actions, that some practices are better known than others (the best known are those related to the environment while the least known are those related with the external stakeholders of the value chain), and that the extent of this knowledge depends on the country where the universities are located. In addition, it was found that the relationship between knowledge and country is not mediated by gender, age, work experience, degree program studied, or year of study. These results suggest that the teaching of social responsibility in Latin American universities does not place equal emphasis on all dimensions of the concept, and that this teaching differs from one country to another.