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Background: Advanced lung diseases are prevalent in women, yet are underrecognized and under-treated due to differing epidemiology and pathophysiology., Aim: To investigate any gender differences in access to palliative care and end-of-life management for patients with advanced lung diseases., Methods: A post-hoc analysis was conducted using three datasets that included information regarding the provision of palliative care to patients with advanced lung diseases - chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung diseases (f-ILD) or non-small cell lung cancer (NSCLC) in tertiary and regional hospitals in Victoria, Australia, from 2004 to 2019., Results: 343 patients with advanced COPD, 67 with f-ILD and 1022 with NSCLC were included. Compared to men, women with COPD (n = 126, 36.7%) were less likely to have smoked ( P = 0.024), had significantly worse lung function ( P < 0.001), and were more likely to receive non-invasive ventilation at end of life ( P = 0.021). Women with fibrotic ILDs (n = 30, 44.8%) had significantly worse lung function ( P < 0.001) and were more likely to experience exacerbations during their last two years of life ( P < 0.001). Women with NSCLC (n = 457, 44.7%) were significantly younger ( P < 0.001), less likely to have smoked ( P < 0.001) or had asbestos exposure ( P < 0.001). There were no significant differences between men and women with advanced lung diseases regarding referral to palliative care services ( P = 0.369), hospital place of death ( P = 0.915), or end-of-life management., Conclusions: Despite differences in lung function, exacerbations and targeted therapies, men and women with advanced lung diseases received equal access to symptom palliation and palliative care services towards the end of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: I confirm that this study has been approved (including for publication) by the Melbourne Health Research Ethics Committee, the Austin Health Human Research Ethics Committee and the Peter MacCallum Cancer Centre Human Research Ethics Committee.

Background: Pancreatoduodenectomy (PD) is a highly complex, invasive, and costly surgical procedure. Limited evidence on the PD volume-cost relationship in countries with a low population density exists. This study aimed to investigate this issue in Australia., Methods: This retrospective cohort study included pancreatic cancer patients who had a PD at any public hospital in New South Wales, Australia between 2016 and 2019. The primary outcome was the total hospital cost during PD admission (not including patient financial burden). Study hospitals were grouped into low-volume hospitals (LVHs; <10 PDs per annum) or high-volume hospitals (HVHs). Multivariable modelling was applied to examine the association between volume and cost., Results: Of 443 PDs, the median total hospital cost per patient at HVHs was AU$55398; significantly lower than that at LVHs (AU$62859; P = 0.001). After adjusting for available patient and clinical factors, the total cost per patient at LVHs was 22% higher than that of HVHs (adjusted estimate: 1.22, 95% CI: 1.08-1.37; P = 0.002). Similar patterns were found in three main cost components: 24% higher employee cost at LVHs than at HVHs (1.24, 95% CI: 1.10-1.41; P < 0.001), 15% higher operating cost (1.15, 95% CI: 1.00-1.31; P = 0.047), and 31% higher other costs (1.31, 95% CI: 1.12-1.53; P < 0.001)., Conclusion: Performance of PDs at HVHs was associated with substantially lower hospital costs. Our findings demonstrate the likely economic benefit of centralizing PDs in countries with a relatively low population density. Future studies should investigate related patient financial burdens., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Purpose: Diet/nutrition is the first-line non-pharmacological therapy in the treatment of diabetes. Diet/nutrition counseling is infrequently provided by primary care providers (PCPs), who have limited nutrition education in both medical and advanced practice provider curricula. This quality improvement project aimed to improve knowledge and attitude, and frequency of diet/nutrition counseling by PCPs among patients with uncontrolled diabetes (glycosylated hemoglobin A1c ≥8%), by providing an online continuing medical education (CME) program on diabetes diet/nutrition., Methods: At a community health center in New England, PCPs attended a live 50-minute online CME program that was developed internally, which taught PCPs current diet/nutrition guidelines and recommendations related to diabetes. Knowledge was assessed prior to and two weeks following the program, utilizing a 10-question tool, the Nutrition Management of Diabetes Assessment (NMDA). Similarly, attitude was evaluated using two subscales of the Nutrition in Patient Care Survey (NIPS): Nutrition in routine care and Physician efficacy. Chart audits of patients with uncontrolled diabetes were evaluated to assess PCPs documentation of diet/nutrition counseling four weeks prior to and six weeks following the CME program., Results: In September 2023, PCPs (n = 29) completed the CME program. There was an improvement in knowledge in the NMDA amongst PCPs (36% difference, p < 0.001). Attitude scores from two subscales of the NIPS were evaluated and both showed improvement, however only physician efficacy was significant (15% difference, p < 0.01). There was a positive difference in the trend of diet/nutrition counseling after the education program (p < 0.05)., Conclusion: An online CME program improved diabetes diet/nutrition knowledge and attitude of PCPs and improved counseling practices for patients living with uncontrolled diabetes. The education program provided PCPs current standards of care guidelines/recommendations, which they can utilize when counseling patients with diabetes. PCPs would benefit from dedicated continuing education programs regarding diet/nutrition therapy for chronic illnesses., Competing Interests: The author(s) report no conflicts of interest in this work., (© 2024 Kahn et al.)

Background: We aimed to estimate the relative risk of mortality following a first positive SARS-CoV-2 test during the first, second, and third waves of the COVID-19pandemic in England by age, sex, and vaccination status, taking into account pre-existing health conditions and lifestyle factors., Methods: We conducted a retrospective cohort study of all individuals registered with the National Health Service (NHS) in England from 1 March 2020 to September 2022. Data for all individuals were obtained and linked including primary care records, hospital admission episodes, SARS-CoV-2 test results, vaccinations, and death registrations. We fitted Cox Proportional Hazards models with time dependent covariates for confirmed SARS-CoV-2 infection to model the risk of subsequent mortality., Results: The hazard ratio for death after testing positive for subsequent, compared with those not testing positive, amongst unvaccinated individuals, ranged from 11 to 89 by age and sex, in the first four weeks following a positive test in wave one and reduced to 14 to 50 in wave three. This hazard was further reduced amongst those who had three vaccines to between 1.4 and 7 in wave three., Conclusions: This study provides robust estimates of increased mortality risk among those who tested positive over the first three waves of the COVID-19 pandemic in England. The estimates show the impact of various factors affecting the risk of mortality from COVID-19. The results provide the first step towards estimating the magnitude and pattern of mortality displacement due to COVID-19, which is essential to understanding subsequent mortality rates in England., Competing Interests: PG declares consultancy payments made from OHID to UCL Consulting to support the preparation of this manuscript. All other authors have no declarations., (Copyright: © 2024 Bauer-Staeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Endovascular embolization is an adjunct to meningioma resection. Isolating the effectiveness of embolization is difficult as MR imaging is typically performed before embolization and after resection, and volumetric assessment of embolization on 2D angiographic imaging is challenging. We investigated the correlation between 2D angiographic and 3D MR measurements of meningioma devascularization following embolization., Methods: We implemented a protocol for postembolization, preresection MRI. Angiographic devascularization was graded according to reduction of tumor blush from 1 (partial embolization) to 4 (complete embolization with no residual circulation supply). Volumetric extent of embolization was quantified as the percent of tumor contrast enhancement lost following embolization. Tumor embolization was analyzed according to tumor location and vascular supply., Results: Thirty consecutive patients met inclusionary criteria. Grade 1 devascularization was achieved in 7% of patients, grade 2 in 43%, grade 3 in 20%, and grade 4 in 30%. Average extent of embolization was 37 ± 6%. Extent of tumor embolization was low (<25%) in 40%, moderate (25%-75%) in 40%, and high (>75%) in 20% of patients. Convexity, parasagittal/falcine and sphenoid wing tumors were found to have distinct vascular supply patterns and extent of embolization. Angiographic devascularization grade was significantly correlated with volumetric extent of tumor embolization ( p  < 0.001, r  = 0.758)., Conclusion: This is the first study to implement postembolization, preoperative MRI to assess extent of embolization prior to meningioma resection. The study demonstrates that volumetric assessment of contrast reduction following embolization provides a quantitative and spatially resolved framework for assessing extent of tumor embolization., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Early cardiopulmonary resuscitation and defibrillation is key to increasing survival following an out-of-hospital-cardiac-arrest (OHCA). However, automated external defibrillators (AEDs) are used in a very small percentage of cases. Despite large numbers of AEDs in the community, the absence of a unified system for registering their locations across the UK's ambulance services may have resulted in missed opportunities to save lives. Therefore, representatives from the resuscitation community worked alongside ambulance services to develop a single repository for data on the location of AEDs in the UK., Methods: A national defibrillator network, "The Circuit", was developed by the British Heart Foundation in collaboration with the Association of Ambulance Chief Executives, the UK ambulance services, the Resuscitation Council UK and St John Ambulance. The database allows individuals or organisations to record information about AED location, accessibility, and availability. The database synchronises with ambulance computer aided dispatch systems to provide UK ambulance services with real-time information on the nearest, available AED., Results: The Circuit was successfully rolled out to all 14 UK ambulance services. Since 2019, 82,108 AEDs have been registered. Of the AED data collected by The Circuit, 54% were not previously registered to any ambulance service, and are therefore new registrations., Conclusion: The Circuit provides ambulance services with a single point of access to AED locations in the UK. Since the launch of the system the number of defibrillators registered has doubled. Linking the Circuit data with patient outcome data will help understand whether improving the accessibility to AEDs is associated with increased survival., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Authors listed as affiliated to the BHF are employees of the BHF, a registered charity in England and Wales, Scotland and the Isle of Man. The BHF is the main funder of The Circuit and responsible for its administration. The author listed as affiliated to NHS England (NHSE) is a former employee of NHSE. NHSE is a co-funder of The Circuit. Authors listed as affiliated to the Resuscitation Council UK (RCUK) are employees of the Resuscitation Council UK a registered charity in England and Wales. The RCUK is a co-funder of The Circuit. Authors listed as affiliated to St John Ambulance (SJA) are employees of St John Ambulance a registered charity in England. SJA is a co-funder of The Circuit. Simon Dunn, Steve Irving, Sue Hampshire, Michael Bradfield, Charles Deakin, Simon Holmes, Stephanie Leckey, Nick Linker, Greg Lloyd, Julian Mark, Lisa McInnes, Simon Walsh, George Woods, Judy O’Sullivan and Gavin D Perkins are current or former members of The Circuit National Advisory Board. GDP holds research grants from the BHF, Resuscitation Council UK and the Laerdal Foundation, is a Trustee for the Resuscitation Council UK and Editor for Resuscitation and Resuscitation Plus journals.’., (© 2024 The Authors.)

We present an interesting case of mycobacterial tuberculosis pericarditis presenting as effusive constrictive pericarditis with early cardiac tamponade in a young Mexican migrant of Haitian descent. The patient underwent a pericardial window and was treated with rifampin, isoniazid, pyrazinamide, ethambutol, and vitamin B6. After further receiving steroids, the patient was doing well and was discharged home safely., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Aim: To assess the equity of care of patients with non-traumatic dental presentations (NTDP) to Christchurch Emergency Department (ED) in Aotearoa New Zealand., Methods: This retrospective observational study reviews NTDP to Christchurch ED over a 2-year period (2018-2020). ED and hospital outcomes were compared for Māori, Pacific peoples and NZ Europeans. Results are interpreted utilising Te Ao Māori principles and discussed referencing a Kaupapa Māori framework., Results: There were a total of 2,034 NTDPs, with Māori (27.0%) and Pacific peoples (6.9%) being over-represented compared to local population estimates (9.4% and 3.2% respectively). Māori experienced shorter wait times (45 minutes, 95% CI 22-86) compared to NZ Europeans (56 minutes, 95% CI 24-97) and Pacific peoples (54 minutes, 95% CI 23-97). Māori had the highest age-standardised incidence of admission, but shorter hospital length of stay (0.9 days, IQR 0.4-2.3) compared to Pacific peoples (3.8 days, IQR 1.8-3.9) and NZ Europeans (2.0 days, IQR 1.0-3.7)., Conclusion: This is the first paper to employ a Kaupapa Māori approach examining NTDP patients presenting to the ED. While outcome measures were largely positive, differences in demographic variables indicate upstream failures, specifically barriers to accessing primary oral healthcare and a paucity of Kaupapa Māori initiatives. Further action and accountability are required to provide high-quality, equitable care for Māori., Competing Interests: Nil., (© PMA.)

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The evolution of nuptial gifts has traditionally been considered a harmonious affair, providing benefits to both mating partners. There is growing evidence, however, that receiving a nuptial gift can be actively detrimental to the female. In decorated crickets ( Gryllodes sigillatus ), males produce a gelatinous spermatophylax that enhances sperm transfer but provides little nutritional benefit and hinders female post-copulatory mate choice. Here, we examine the sexually antagonistic coevolution of the spermatophylax and the female feeding response to this gift in G. sigillatus maintained in experimental populations with either a male-biased or female-biased adult sex ratio. After 25 generations, males evolving in male-biased populations produced heavier spermatophylaxes with a more manipulative combination of free amino acids than those evolving in female-biased populations. Moreover, when the spermatophylax originated from the same selection regime, females evolving in male-biased populations always had shorter feeding durations than those evolving in female-biased populations, indicating the evolution of greater resistance. Across populations, female feeding duration increased with the mass and manipulative combination of free amino acids in the spermatophylax, suggesting sexually antagonistic coevolution. Collectively, our work demonstrates a key role for interlocus sexual conflict and sexually antagonistic coevolution in the mating system of G. sigillatus .

We study the modulational dynamics of striped patterns formed in the wake of a planar directional quench. Such quenches, which move across a medium and nucleate pattern-forming instabilities in their wake, have been shown in numerous applications to control and select the wavenumber and orientation of striped phases. In the context of the prototypical complex Ginzburg-Landau and Swift-Hohenberg equations, we use a multiple-scale analysis to derive a one-dimensional viscous Burgers' equation, which describes the long-wavelength modulational and defect dynamics in the direction transverse to the quenching motion, that is, along the quenching line. We show that the wavenumber selecting properties of the quench determine the nonlinear flux parameter in the Burgers' modulation equation, while the viscosity parameter of the Burgers' equation is naturally determined by the transverse diffusivity of the pure stripe state. We use this approximation to accurately characterize the transverse dynamics of several types of defects formed in the wake, including grain boundaries and phase-slips., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objectives: To evaluate the safety and efficacy of first-trimester "No Touch" medication abortion programs at 2 clinics in Toronto, Ontario during their early implementation in response to the COVID-19 pandemic., Methods: This retrospective study included all patients who underwent virtual consultation for mifepristone-misoprostol medication abortion between April 2020-August 2022 at 2 reproductive health clinics. In response to the pandemic, "No Touch" abortion protocols have been developed that align with the Canadian Protocol for the Provision of Medical Abortion via Telemedicine. Records were reviewed for demographic information, clinical course, investigations required, confirmation of complete abortion and adverse events. The primary outcome was complete medication abortion, defined as expulsion of the pregnancy without requiring uterine aspiration., Results: A total of 277 patients had abortions initiated in the "No Touch" or "Low Touch" care pathways and had sufficient follow-up to determine outcomes. Of these patients, 92.8% (95% CI 89.7%-95.8%) had a complete medication abortion (n = 257) and 76.1% (n = 159) remained "No Touch" throughout their care. Investigations were performed for 102 participants before or after their abortion, classifying them as "Low Touch". Nineteen patients (6.9%) underwent uterine aspiration. The rate of adverse events was low, with 1 case of a missed ectopic pregnancy and 1 patient requiring hospitalization for endometritis., Conclusions: "No Touch" provision of mifepristone-misoprostol medication abortion care was safe and effective with outcomes comparable to previous studies. These results provide evidence for the efficacy and safety of a "No Touch" approach in the Canadian context, which has the potential to reduce barriers to accessing abortion care., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Enzymes are nature's catalysts, mediating chemical processes in living systems. The study of enzyme function and mechanism includes defining the maximum catalytic rate and affinity for substrate/s (among other factors), referred to as enzyme kinetics. Enzyme kinetics is a staple of biochemistry curricula and other disciplines, from molecular and cellular biology to pharmacology. However, because enzyme kinetics involves concepts rarely employed in other areas of biology, it can be challenging for students and researchers. Traditional graphical analysis was replaced by computational analysis, requiring another skill not core to many life sciences curricula. Computational analysis can be time-consuming and difficult in free software (e.g., R) or require costly software (e.g., GraphPad Prism). We present Enzyme Kinetics Analysis (EKA), a web-tool to augment teaching and learning and streamline EKA. EKA is an interactive and free tool for analyzing enzyme kinetic data and improving student learning through simulation, built using R and RStudio's ShinyApps. EKA provides kinetic models (Michaelis-Menten, Hill, simple reversible inhibition models, ternary-complex, and ping-pong) for users to fit experimental data, providing graphical results and statistics. Additionally, EKA enables users to input parameters and create data and graphs, to visualize changes to parameters (e.g., K M or number of measurements). This function is designed for students learning kinetics but also for researchers to design experiments. EKA (enzyme-kinetics.shinyapps.io/enzkinet&#95;webpage/) provides a simple, interactive interface for teachers, students, and researchers to explore enzyme kinetics. It gives researchers the ability to design experiments and analyze data without specific software requirements., (© 2024 The Authors. Biochemistry and Molecular Biology Education published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

There is increasing demand to power Internet of Things devices using ambient energy sources. Flexible, low-temperature, organic/inorganic thermoelectric devices are a breakthrough next-generation approach to meet this challenge. However, these systems suffer from poor performance and expensive processing preventing wide application of the technology. In this study, by combining a ferroelectric polymer (Polyvinylidene fluoride (PVDF, β phase)) with p-type Bi 0.5 Sb 1.5 Te 3 (BST) a thermoelectric composite film with maximum is produced power factor. Energy filter from ferroelectric-thermoelectric junction also leads to high Seebeck voltage ≈242 µV K -1 . For the first time, compelling evidence is provided that the dipole of a ferroelectric material is helping decouple electron transport related to carrier mobility and the Seebeck coefficient, to provide 5× or more improvement in thermoelectric power factor. The best composition, PVDF/BST film with BST 95 wt.% has a power factor of 712 µW•m -1  K -2 . A thermoelectric generator fabricated from a PVDF/BST film demonstrated P max T 12.02 µW and P density 40.8 W m -2 under 50 K temperature difference. This development also provides a new insight into a physical technique, applicable to both flexible and non-flexible thermoelectrics, to obtain comprehensive thermoelectric performance., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

Background/objective: To explore the anti-tumour activity of combining AKT inhibition and docetaxel in PTEN protein null and WT prostate tumours., Methods: Mechanisms associated with docetaxel capivasertib treatment activity in prostate cancer were examined using a panel of in vivo tumour models and cell lines., Results: Combining docetaxel and capivasertib had increased activity in PTEN null and WT prostate tumour models in vivo. In vitro short-term docetaxel treatment caused cell cycle arrest in the majority of cells. However, a sub-population of docetaxel-persister cells did not undergo G2/M arrest but upregulated phosphorylation of PI3K/AKT pathway effectors GSK3β, p70S6K, 4E-BP1, but to a lesser extent AKT. In vivo acute docetaxel treatment induced p70S6K and 4E-BP1 phosphorylation. Treating PTEN null and WT docetaxel-persister cells with capivasertib reduced PI3K/AKT pathway activation and cell cycle progression. In vitro and in vivo it reduced proliferation and increased apoptosis or DNA damage though effects were more marked in PTEN null cells. Docetaxel-persister cells were partly reliant on GSK3β as a GSK3β inhibitor AZD2858 reversed capivasertib-induced apoptosis and DNA damage., Conclusion: Capivasertib can enhance anti-tumour effects of docetaxel by targeting residual docetaxel-persister cells, independent of PTEN status, to induce apoptosis and DNA damage in part through GSK3β., (© 2024. The Author(s).)

Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These 'persister' cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients., (© 2024. The Author(s).)

Background: The British Columbia Farmers' Market Nutrition Coupon Program (BC FMNCP) provides households with low incomes with coupons to purchase healthy foods from farmers' markets., Objective: To examine the impact of the BC FMNCP on the short-term household food insecurity, malnutrition risk, mental well-being, sense of community (secondary outcomes), and subjective social status (exploratory outcome) of adults with low incomes post-intervention and 16 weeks post-intervention., Design: Secondary analyses from a pragmatic randomized controlled trial conducted in 2019 that collected data at baseline, post-intervention, and 16 weeks post-intervention., Participants/setting: Adults ≥18 years with low incomes were randomized to an FMNCP group (n = 143) or a no-intervention control group (n = 142)., Intervention: Participants in the FMNCP group received 16 coupon sheets valued at $21 Canadian dollars (CAD)/sheet over 10 to 15 weeks to purchase healthy foods from farmers' markets and were eligible to participate in nutrition skill-building activities., Main Outcome Measures: Outcomes included short-term household food insecurity (modified version of Health Canada's 18-item Household Food Security Survey Module), malnutrition risk (Malnutrition Universal Screening Tool), mental well-being (Warwick-Edinburgh Mental Well-Being Scale), sense of community (Brief Sense of Community Scale), and subjective social status (MacArthur Scale of Subjective Social Status community scale)., Statistical Analysis: Mixed-effects linear regression and multinomial logistic regression examined between-group differences in outcomes post-intervention and 16 weeks post-intervention., Results: The risk of marginal and severe short-term household food insecurity was lower among those in the FMNCP group compared with those in the control group (relative risk ratio [RRR] 0.15, P = 0.01 and RRR 0.16, P = 0.02) post-intervention, with sustained reductions in severe household food insecurity 16 weeks post-intervention (RRR 0.11, P = 0.01). No statistically significant differences were observed in malnutrition risk, mental well-being, sense of community, or subjective social status post-intervention or 16 weeks post-intervention., Conclusions: The BC FMNCP reduced short-term household food insecurity but was not found to improve malnutrition risk or psychosocial well-being among adults with low incomes compared with a no-intervention control group., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: The current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections., Methods: We developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using "eNTRy rules" criteria associated with increased likelihood of intracellular accumulation in Escherichia coli., Findings: We identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC 50  ≤50 μM) and absence of cytotoxicity (HepG2 CC 50  ≥100 μM and red blood cell lysis HC 50  ≥100 μM). The activity of close analogues of the two chemical series was also determined against A. baumannii clinical isolates., Interpretation: This work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects., Funding: BMBF and GARDP., Competing Interests: Declaration of interests Small-molecule libraries were provided by Takeda Pharmaceutical Company Ltd, Eisai Co., Ltd and Daiichi Sankyo Co., Ltd. Yuichiro Akao, Atsuko Ochida, Nao Morishita, Terufumi Takagi, Hiroyuki Nagamiya are employees of Takeda Pharmaceutical Company Ltd. Yamato Suzuki and Toshiaki Watanabe are employees of Daiichi Sankyo Co., Ltd. HKR performed her contributions while employed at GARDP but is now employed by AMR Action Fund. SD received payments as part of a consultancy agreement with GARDP to carry out tasks including genomic data curation and analysis, figure generation, and data analysis. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: 37.5% of deaths in our area occur in hospital. There are known high unmet needs of adult patients dying in hospital, this unmet need can be reduced by using an individualised care plan and specialist palliative care review. Intervention: In 2022 UHSussex developed an electronic comfort observation chart and individualised care plan, with a centralised dashboard allowing Palliative Care Teams (SPCT) to view trends, target interventions, and a rolling prospective audit. Results: 3000 patients have had their care supported with electronic comfort observations (e-comfort obs). Over 72% of all deaths in the Trust in the last 3 months have been on e-comfort obs, with 2/3 of all deaths in the first 12 months on e-comfort obs. The average length of time on e-comfort obs is 4 days resulting in 70,000 sets of e-comfort obs recorded since launch. Seven percent of e-comfort obs record moderate or severe symptoms. We have identified benefits to people who are dying, those important to them, ward staff, SPCT and on a systems level. Conclusion: E-comfort obs can be successfully embedded in a large acute Trust. This development should improve quality of end of life care in our hospitals both for individuals and for future patients, through on-going targeted education and intervention. Further work is needed to develop the system further including integrating data from electronic prescribing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: FoodRx is a 12-month healthy food prescription incentive program for people with type 2 diabetes (T2DM) and experiences of household food insecurity. In this study, we aimed to explore potential users' prospective acceptability (acceptability prior to program use) of the design and delivery of the FoodRx incentive and identify factors influencing prospective acceptability., Design: We used a qualitative descriptive approach and purposive sampling to recruit individuals who were interested or uninterested in using the FoodRx incentive. Semi-structured interviews were guided by the theoretical framework of acceptability, and corresponding interview transcripts were analysed using differential qualitative analysis guided by the socioecological model., Setting: Individuals living in Alberta, Canada., Participants: In total, fifteen adults with T2DM and experiences of household food insecurity., Results: People who were interested in using the FoodRx incentive ( n 10) perceived it to be more acceptable than those who were uninterested ( n 5). We identified four themes that captured factors that influenced users' prospective acceptability: (i) participants' confidence, views and beliefs of FoodRx design and delivery and its future use (intrapersonal), (ii) the shopping routines and roles of individuals in participants' social networks (interpersonal), (iii) access to and experience with food retail outlets (community), and (iv) income and food access support to cope with the cost of living (policy)., Conclusion: Future healthy food prescription programs should consider how factors at all levels of the socioecological model influence program acceptability and use these data to inform program design and delivery.

Background: Parkinson's disease can negatively affect vocal functioning and social wellbeing, particularly in the latter stages of disease progression. Face-to-face group singing interventions can improve communication and wellbeing outcomes, yet not all people can access in-person sessions. To help overcome barriers to participation, exploration of the feasibility and utility of online therapeutic singing programs is needed., Objectives: To evaluate the feasibility, acceptability, and preliminary efficacy of a 12-week ParkinSong Online intervention on speech and wellbeing for people with Parkinson's disease., Methods: A total of 28 participants with idiopathic Parkinson's disease were recruited to a single-arm feasibility study. Weekly 90-minute online sessions were co-facilitated by a music therapist and speech pathologist. Speech and wellbeing assessments were conducted pre and post intervention. Participant and facilitator surveys were administered after each session, with focus group interviews at the end of the program., Results: The recruitment rate was high (90%) with no attrition, adverse events, or safety issues. There was good intervention fidelity, attendance (average 89%), and positive participant experience. Feasibility was good, with technology reported as the main challenge (connecting and navigating Zoom). No improvements were seen in voice measures or wellbeing outcomes in this small trial. The online format used in this study did not provide the same benefits as in-person ParkinSong sessions., Conclusions: ParkinSong Online is feasible for recreational purposes and social engagement provided that people have adequate technological knowledge or support. The optimal online delivery format to achieve communication improvements in Parkinson's awaits confirmation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Type IV pili (T4Ps) are surface filaments widely distributed among bacteria and archaea. T4Ps are involved in many cellular functions and contribute to virulence in some species of bacteria. Due to the diversity of T4Ps, different properties have been observed for homologous proteins that make up T4Ps in various organisms. In this review, we highlight the essential components of T4Ps, their functions, and similarities to related systems. We emphasize the unique T4Ps of enteric pathogens within the Enterobacteriaceae family, which includes pathogenic strains of Escherichia coli and Salmonella . These include the bundle-forming pilus (BFP) of enteropathogenic E. coli (EPEC), longus (Lng) and colonization factor III (CFA/III) of enterotoxigenic E. coli (ETEC), T4P of Salmonella enterica serovar Typhi, Colonization Factor Citrobacter (CFC) of Citrobacter rodentium , T4P of Yersinia pseudotuberculosis , a ubiquitous T4P that was characterized in enterohemorrhagic E. coli (EHEC), and the R64 plasmid thin pilus. Finally, we highlight areas for further study.

Objective: Individuals with psychosis are at elevated risk of adverse sexual and reproductive health (SRH) outcomes, and not receiving adequate SRH care. SRH is important for youth, yet little is known about SRH care access and experiences among those with early psychosis. This study explored SRH care experiences among women and nonbinary individuals with early psychosis., Method: We conducted semistructured qualitative interviews with 19 service users (cisgender and transgender women, nonbinary individuals) receiving care in 2 early psychosis programs in Ontario, Canada. We also conducted semistructured interviews and focus groups with 36 clinicians providing SRH or mental health care to this population. Participants were asked about SRH care access/provision experiences and the interplay with psychosis. Using a social interactionist orientation, a thematic analysis described and explained service user and clinician perspectives regarding SRH care., Results: Amongst both service users and clinician groups, common themes developed: (a) diversity of settings: SRH services are accessed in a large range of spaces across the health care system, (b) barriers in nonpsychiatric SRH care settings: psychosis impacts the ability to engage with existing SRH services, (c) invisibility of SRH in psychiatric settings: SRH is rarely addressed in psychiatric care, (d) variability of informal SRH-related conversations and supports, and cutting across all of the above themes, (e) intersecting social and cultural factors impacted SRH services access., Conclusions: SRH is important for health and wellbeing; improvements are urgently needed across the healthcare system and within early psychosis programs to meet this population's multifaceted SRH needs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SNV reports royalties from UpToDate for authorship of materials related to antidepressants and pregnancy. RG reports royalties from UpToDate for authorship of an article related to Pseudocyesis. RD reports financial support from Searchlight Pharma, Merck, and Bayer. ANV receives funding from the National Institute of Mental Health, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto. All other authors report having nothing to disclose.

We report external bias driven switchable photocurrent (anodic and cathodic) in 2.3 eV indirect band gap perovskite (BiFeO 3 ) photoactive thin films. Depending on the applied bias our BiFeO 3 films exhibit photocurrents more usually found in p- or n-type semiconductor photoelectrodes. In order to understand the anomalous behaviour ambient photoemission spectroscopy and Kelvin-probe techniques have been used to determine the band structure of the BiFeO 3 . We found that the Fermi level ( E f ) is at -4.96 eV ( vs . vacuum) with a mid-gap at -4.93 eV ( vs . vacuum). Our photochemically determined flat band potential ( E fb ) was found to be 0.3 V vs . NHE (-4.8 V vs . vacuum). These band positions indicate that E f is close to mid-gap, and E fb is close to the equilibrium with the electrolyte enabling either cathodic or anodic band bending. We show an ability to control switching from n- to p-type behaviour through the application of external bias to the BiFeO 3 thin film. This ability to control majority carrier dynamics at low applied bias opens a number of applications in novel optoelectronic switches, logic and energy conversion devices.

Competing Interests: Intérêts concurrents : Lora Giangregorio déclare avoir reçu des honoraires d’Amgen Inc. pour une conférence donnée sur l’exercice physique, hors du cadre du présent manuscrit, sans mention de médicaments. La Dre Giangregorio est également membre du conseil consultatif scientifique d’Ostéoporose Canada et coresponsable du Groupe d’intérêt spécial sur la fracture vertébrale du Fragility Fracture Network. Sandra Kim déclare qu’Ostéoporose Canada lui a offert le soutien d’une personne spécialiste de la méthodologie GRADE (Grading of Recommendations, Assessment, Development and Evaluations) à l’Université McMaster au cours de l’étude. De 2017 à 2020, la Dre Kim a aussi été membre bénévole du conseil d’administration d’Ostéoporose Canada. Nancy Santesso déclare avoir reçu une rémunération versée à son établissement (Université McMaster) afin d’apporter son expertise de l’outil GRADE à l’élaboration des lignes directrices et à la préparation de contenus au cours de l’étude. La Dre Santesso a aussi reçu du soutien d’Ostéoporose Canada pour se rendre aux réunions sur les lignes directrices. Heather McDonald-Blumer déclare avoir reçu des honoraires de consultation d’Eli Lilly et de Novartis pour sa présence à des conseils consultatifs, sans lien avec les présents travaux. Rowena Ridout est membre du conseil d’administration d’Ostéoporose Canada depuis 2020 (aucune rémunération perçue). Neil Binkley déclare avoir reçu une subvention de recherche (versée à son établissement) de Radius, ainsi que des frais de consultation et des honoraires d’Amgen. Angela Cheung a reçu des honoraires d’Amgen et des Laboratoires Paladin à titre de consultante. La Dre Cheung a aussi été membre du comité des lignes directrices cliniques de l’Endocrine Society, coprésidente du programme de santé postménopause de l’American College of Obstetrics and Gynecology et vice-présidente et coresponsable de la Conférence de prise de position 2023 de la Société internationale de densitométrie clinique. Robert Josse déclare avoir reçu des frais de consultation d’Amgen Canada, des Laboratoires Paladin et d’Alexion, ainsi que des honoraires d’Amgen et d’Alexion. Le Dr Josse a aussi participé à des comités consultatifs pour Amgen, Paladin, Alexion et Ultragenyx. Aliya Khan a reçu des subventions de recherche d’Alexion, d’Amgen Canada, de Takeda, d’Ascendis, de Chugai, de Radius, d’Amolyt et d’Ultragenyx, ainsi que des honoraires de conférencière d’Amgen, d’Alexion, d’Ascendis, de Takeda et d’Ultragenyx. La Dre Khan a également participé à des comités consultatifs pour Amgen Canada, Alexion, Amolyt, Ascendis et Takeda. E. Lynn Izumi Nash déclare que le Collège des médecins de famille de l’Ontario lui a versé des honoraires pour la conception d’ateliers de formation médicale continue sur l’ostéoporose. La Dre Nash est aussi membre du conseil consultatif scientifique d’Ostéoporose Canada (à titre bénévole). Zahra Bardai déclare avoir reçu des honoraires en tant que membre du comité de planification scientifique de Pri-Med Canada depuis 2011 et en tant que créatrice du Programme d’apprentissage basé sur la pratique en petit groupe de la Fondation pour l’éducation médicale continue, à l’Université McMaster. La Dre Bardai est aussi membre bénévole du conseil consultatif scientifique d’Ostéoporose Canada. Suzanne Cadarette déclare avoir reçu des subventions de recherche (versées à son établissement) en tant que cochercheuse principale pour des projets financés par les Instituts de recherche en santé du Canada et les National Institutes of Health. Heather Frame a siégé au conseil d’administration d’Ostéoporose Canada jusqu’en novembre 2020. Kaleen Hayes déclare avoir reçu des subventions de recherche à l’initiative des chercheurs du National Institute on Aging, d’Insight Therapeutics, de Genentech et de Sanofi (versées directement à son établissement), et des honoraires de consultation de l’Agence canadienne des médicaments et des technologies de la santé. Alexandra Papaioannou a fait partie d’un comité consultatif et de services de conférenciers et conférencières et a reçu des honoraires d’Amgen Canada. Christine Thomas a été membre du conseil d’administration d’Ostéoporose Canada à différentes périodes.

In sub-Saharan Africa, sexual relationships between younger women and older men have been shown to pose a risk of HIV transmission. In South Africa, there has been growing interest in blesser-blessee relationships. This study explores perceptions of these relationships among university students in Durban, South Africa. The study draws on 15 in-depth interviews with students. Participants suggest that older men engage in these relationships for sexual gratification and younger women do so for monetary or material gain. Interviews revealed that participants believed that these relationships are common with both men and women engaging in them and putting themselves at risk of HIV infection. It is imperative to explore the context and motivation for these relationships because of their broader social and health implications. In addition, greater effort should be geared towards addressing the underlying factors that facilitate blesser-blessee relationships.

Background: Near-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed "harvesting" in the literature., Methods: We present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a "ball and urn" model., Results: Among the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy., Conclusion: Our results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement - both in its length and prevalence - by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older., Methods: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework., Recommendations: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized., Interpretation: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life., Competing Interests: Competing interests: Lora Giangregorio reports receiving an honorarium from Amgen Inc. for a lecture on exercise with no mention of medications, outside the current manuscript. Dr. Giangregorio is also a member of the Scientific Advisory Council of Osteoporosis Canada and co-lead of the Vertebral Fracture Special Interest Group, Fragility Fracture Network. Sandra Kim reports receiving support from Osteoporosis Canada for a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodologist at McMaster University, during the conduct of the study. Dr. Kim was also a volunteer member of the Osteoporosis Canada Board of Directors from 2017 to 2020. Nancy Santesso reports receiving payment to provide GRADE expertise for guideline development and preparation of materials paid to institution (McMaster University), during the conduct of the study. Dr. Santesso has also received support from Osteoporosis Canada for travel to guideline-related meetings. Heather McDonald-Blumer reports receiving consulting fees from Eli Lilly and Novartis, for attendance on advisory boards, outside the submitted work. Rowena Ridout has been a member of the Osteoporosis Canada Board of Directors since 2020 (no payment received). Neil Binkley reports receiving a research grant (paid to institution) from Radius, and consulting fees and honoraria from Amgen. Angela Cheung has received honoraria for consultancy work from Amgen and Paladin Laboratories. Dr. Cheung has also held the following roles: member of the Clinical Guidelines Committee of the Endocrine Society; co-chair of the postmenopausal health pathway, American College of Obstetrics and Gynecology; and vice-president and co-chair of the 2023 Position Development Conference, International Society for Clinical Densitometry. Robert Josse reports receiving consulting fees from Amgen Canada, Paladin Laboratories and Alexion, and honoraria from Amgen and Alexion. Dr. Josse has also participated on advisory boards for Amgen, Paladin, Alexion and Ultragenyx. Aliya Khan has received research grants from Alexion, Amgen Canada, Takeda, Ascendis, Chugai, Radius, Amolyt and Ultragenyx, and speaker honoraria from Amgen, Alexion, Ascendis, Takeda and Ultragenyx. Dr. Khan has also participated on advisory boards for Amgen Canada, Alexion, Amolyt, Ascendis and Takeda. E. Lynn Izumi Nash reports receivin an honorarium from the Ontario College of Family Physicians for designing continuing medical education workshops on osteoporosis. Dr. Nash is also a member of the Scientific Advisory Council for Osteoporosis Canada (voluntary unpaid position). Zahra Bardai reports receiving honoraria as a member of the Pri-Med Canada Scientific Planning Committee (2011–present) and as an author of the Foundation for Medical Practice Education Small Group Practice–Based Learning Program, at McMaster University. Dr. Bardai is also a volunteer member of the Osteoporosis Canada Scientific Advisory Council. Suzanne Cadarette reports receiving research funds (paid to institution) as co–principal investigator on Canadian Institutes of Health Research and National Institutes of Health project grants. Heather Frame is a former member of the Osteoporosis Canada Board of Directors (term ended November 2020). Kaleen Hayes reports receiving researcher-initiated grants from the National Institute on Aging, Insight Therapeutics, Genentech and Sanofi (all paid directly to institution), and consulting fees from the Canadian Agency for Drugs and Technologies in Health. Alexandra Papaioannou has participated on an advisory board and in speakers’ bureaus and received honoraria from Amgen Canada. Christine Thomas has been a member of the Osteoporosis Canada Board of Directors at various time points. Conflict-of-Interest Oversight Committee: Heather McDonald-Blumer (Chair), Larry Funnell, Rowena Ridout., (© 2023 CMA Impact Inc. or its licensors.)

When expressing complex biotherapeutic proteins, traditional expression plasmids and methods may not always yield sufficient levels of high-quality product. High-strength viral promoters commonly used for recombinant protein (rProtein) production in mammalian cells allow for maximal expression, but provide limited scope to alter their transcription dynamics. However, synthetic promoters designed to provide tunable transcriptional activity offer a plasmid engineering approach to more precisely regulate product quality, yield or to reduce product related contaminants. We substituted the viral promoter CMV with synthetic promoters that offer different transcriptional activities to express our gene of interest in Chinese hamster ovary (CHO) cells. Stable pools were established and the benefits of regulating transgene transcription on the quality of biotherapeutics were examined in stable pool fed-batch overgrow experiments. Specific control of gene expression of the heavy chain (HC):light chain (LC) of a Fab, and the ratio between the two HCs in a Duet mAb reduced levels of aberrant protein contaminants; and the controlled expression of the helper gene XBP-1s improved expression of a difficult-to-express mAb. This synthetic promoter technology benefits applications that require custom activity. Our work highlights the advantages of employing synthetic promoters for production of more complex rProteins., (© 2023 AstraZeneca PLC. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Objectives: Opioids may impair the ability to drive safely, particularly when first prescribed or with dose titration. We investigated whether clinicians evaluate driving status and provide opioid-related driving advice when initiating opioids among people with advanced lung cancer., Methods: A retrospective medical record review of outpatients with advanced non-small cell lung cancer seen at an Australian tertiary referral centre between 1 January 2015 and 31 December 2019 was undertaken to determine frequency of opioid prescription and documentation of driving status and education regarding driving safety while taking opioids., Results: Of 1022 patients screened, 205 were commenced on opioid therapy. Forty-seven (23%) patients had driving status documented. According to medical records, education about driving safety while on opioids was provided to two (1%) patients on opioid initiation. Ten (5%) patients received opioid-related driving education at least once at follow-up appointments. The content of the education was infrequently documented, and when documented, focused on opioid side effects impacting driving. Opioid doses were often escalated at follow-up appointments., Conclusions: According to documentation in medical records, clinicians infrequently assessed driving status on opioid initiation and rarely provided education regarding opioid-related driving risks. Further research and clearer guidance regarding opioids and driving safety in the cancer population are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Women and gender-diverse people with early psychosis are at risk for suboptimal sexual health outcomes, yet little research has explored their sexual health experiences., Aims: This study explored sexual health experiences and related priorities among women and gender-diverse people with early psychosis, to identify opportunities for improvements in sexual health and well-being., Method: Semi-structured individual qualitative interviews explored how patient participants ( n = 19, aged 18-31 years, cisgender and transgender women and non-binary individuals) receiving clinical care from early psychosis programmes in Ontario, Canada, experienced their sexual health, including sexual function and behaviour. Thematic analysis was conducted, with triangulation from interviews/focus groups with clinicians ( n = 36) who provide sexual and mental healthcare for this population., Results: Three key themes were identified based on patient interviews: theme 1 was the impact of psychotic illness and its treatments on sexual function and activity, including variable changes in sex drive, attitudes and behaviours during acute psychosis, vulnerability to trauma and medications; theme 2 related to intimacy and sexual relationships in the context of psychosis, with bidirectional effects between relationships and mental health; and theme 3 comprised autonomy, identity and intersectional considerations, including gender, sexuality, culture and religion, which interplay with psychosis and sexual health. Clinicians raised each of these priority areas, but emphasised risk prevention relative to patients' more holistic view of their sexual health and well-being., Conclusions: Women and non-binary people with early psychosis have wide-ranging sexual health priorities, affecting many facets of their lives. Clinical care should incorporate this knowledge to optimise sexual health and well-being in this population.

Background: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia., Methods: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England., Results: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures., Conclusions: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hybridization capture approaches allow targeted high-throughput sequencing analysis at reduced costs compared to shotgun sequencing. Hybridization capture is particularly useful in analyses of genomic data from ancient, environmental, and forensic samples, where target content is low, DNA is fragmented and multiplex PCR or other targeted approaches often fail. Here, we describe a DNA bait synthesis approach for hybridization capture that we call Circular Nucleic acid Enrichment Reagent, or CNER (pronounced 'snare'). The CNER method uses rolling-circle amplification followed by restriction digestion to discretize microgram quantities of hybridization probes. We demonstrate the utility of the CNER method by generating probes for a panel of 23 771 known sites of single nucleotide polymorphism in the horse genome. Using these probes, we capture and sequence from a panel of ten ancient horse DNA libraries, comparing CNER capture efficiency to a commercially available approach. With about one million read pairs per sample, CNERs captured more targets (90.5% versus 66.5%) at greater mean depth than an alternative commercial approach., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To evaluate the care of patients dying in hospital without support from specialists in palliative care (SPC), better understand their needs and factors influencing their care., Methods: Prospective UK-wide service evaluation including all dying adult inpatients unknown to SPC, excluding those in emergency departments/intensive care units. Holistic needs were assessed through a standardised proforma., Results: 88 hospitals, 284 patients. 93% had unmet holistic needs, including physical symptoms (75%) and psycho-socio-spiritual needs (86%). People were more likely to have unmet needs and require SPC intervention at a district general hospital (DGH) than a teaching hospital/cancer centre (unmet need 98.1% vs 91.2% p0.02; intervention 70.9% vs 50.8% p0.001) and when end-of-life care plans (EOLCP) were not used (unmet need 98.3% vs 90.3% p0.006; intervention 67.2% vs 53.3% p0.02). Multivariable analyses demonstrated the independent influence of teaching/cancer hospitals (adjusted OR (aOR)0.44 CI 0.26 to 0.73) and increased SPC medical staffing (aOR1.69 CI 1.04 to 2.79) on need for intervention, however, integrating the use of EOLCP reduced the impact of SPC medical staffing., Conclusion: People dying in hospitals have significant and poorly identified unmet needs. Further evaluation is required to understand the relationships between patient, staff and service factors influencing this. The development, effective implementation and evaluation of structured individualised EOLCP should be a research funding priority., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite known analgesic effects of breastfeeding (BF), skin-to-skin care (SSC), and sweet solutions (sucrose) for newborns, these interventions remain underutilized. Our team produced a five-minute parent-targeted video (BSweet2Babies) demonstrating BF, SSC, and sucrose during newborn blood sampling. We conducted a sequential exploratory mixed-methods study with eight maternal-newborn units across Ontario, Canada to identify barriers and facilitators to implementing the video and the three pain management strategies.Over a 6-month period, data collection included 15 telephone interviews, two email communications, and three community of practice teleconferences with the participating sites ( n = 8). We used the Theoretical Domains Framework as the coding matrix. Participants discussed integrating the video in prenatal education and the importance of involving leadership when planning for practice change. Key barriers included lack of comfort with parental presence, perception of high complexity of the strategies, short postpartum stays, competing priorities, and interprofessional challenges. Key facilitators included alignment with the Baby-Friendly Hospital Initiative, modeling by Lactation Consultants, and frequent reminders.

Objective: Difficulties with dissociation and emotion regulation are well-documented reactions to early adverse childhood experiences (ACEs). Although findings identify dissociation and emotion dysregulation as explaining the relationship between various forms of ACEs and adult psychopathology, less is known about their combined effect in the relationship between ACEs and insecure attachment in adulthood. This study examined the indirect effects of dissociation and emotion regulation difficulties in the relationship between early adverse experiences and insecure attachment traits., Method: Participants ( N = 260) completed an online questionnaire measuring ACEs, dissociation, emotion regulation difficulties, and anxious and avoidant attachment., Results: Results indicated that, after controlling for mental health treatment, dissociation and emotion regulation difficulties explained the relationship between ACEs and insecure (anxious and avoidant) attachment. Emotion regulation difficulties were not a significant predictor of avoidant attachment., Conclusion: Findings provide support for greater research on mediating factors in the maintenance of insecure attachment across development and potential implications of dissociation and emotion regulation in clinical and nonclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: Vasopressin may be administered to treat vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). The objectives of this study were to describe five cases of suspected vasopressin-induced hyponatremia after aSAH and to review the literature. Design: Single-center, observational case series of intensive care unit (ICU) patients. Settings: Ten-bed neurological ICU at Maine Medical Center in Portland, Maine. Patients: Convenience sample of patients with aSAH treated with a vasopressin for symptomatic, radiologically confirmed vasospasm. Results: A total of five patients were included in the case series with a median age of 57 (51, 65) years and all were women. The median Glasgow coma scale score was 15 (11, 15) on admission, and the Hunt and Hess scale score was 3, (3, 4). All patients were treated with endovascular coiling of their aneurysm. Vasopressin was administered to treat symptomatic, radiographically confirmed vasospasm on median post-bleed day (PBD) 10 (10, 15) at a fixed-dose of .03 units/min. Serum sodium at baseline was 140 (140, 144) mEq/L and decreased to 129 (126, 129) mEq/L within 26 (17, 83) hours of vasopressin initiation for a median change of -16 (-10, -16) mEq/L. Serum sodium returned to baseline within 18 (14, 22) hours of stopping the infusion. Conclusions: Vasopressin use in vasospasm after aSAH may be associated with clinically significant hyponatremia within 24 hours of starting the infusion. Hyponatremia appears to resolve within 24 hours of stopping the infusion. Additional study in a larger sample size is needed to determine if a causal relationship exist.

Elevated concentrations of potassium (K) often occur in effluents from wastewater treatment plants, oil and gas production operations, mineral extraction processes, and other anthropogenic sources. Previous studies have demonstrated that freshwater mussels are highly sensitive to K in acute and chronic exposures, and that acute toxicity of K decreases with increasing water hardness. However, little is known about the influence of hardness on the chronic toxicity of K. The objective of our study was to evaluate the chronic toxicity of K (tested as KCl) to a commonly tested unionid mussel (fatmucket, Lampsilis siliquoidea) at five hardness levels (25, 50, 100, 200, and 300 mg/L as CaCO 3 ) representing most surface waters in the United States. Chronic 28-day K toxicity tests were conducted with 3-week-old juvenile fatmucket in the five hardness waters using an ASTM International standard method. The maximum acceptable toxicant concentrations (geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) increased from 15.1 to 69.3 mg K/L for survival and from 15.1 to 35.8 mg K/L for growth (length and dry wt) and biomass when water hardness was increased from 25 mg/L (soft) to 300 mg/L (very hard). These results provide evidence to support water hardness influence on chronic K toxicity to juvenile fatmucket. However, the chronic effect concentrations based on the more sensitive endpoint (growth or biomass) increased only 2.4-fold from the soft water to the very hard water, indicating that water hardness had a limited influence on the chronic toxicity of K to the mussels. These results can be used to establish chronic toxicity thresholds for K across a broad range of water hardness and to derive environmental guideline values for K to protect freshwater mussels and other organisms. Environ Toxicol Chem 2023;42:1085-1093. Published 2023. This article is a U.S. Government work and is in the public domain in the USA., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Telemedicine has the potential to improve abortion access disparities in Canada. We aimed to explore the provision of telemedicine for first-trimester medical abortion and related barriers in 2019. Methods: We conducted a national, cross-sectional, anonymized, web-based survey of clinicians who provided abortion care in 2019 in Canada. We distributed our survey through professional health organizations to maximize identification of possible eligible respondents and used a modified Dillman technique to foster responses. Questions elicited provider demographics, clinical characteristics, including telemedicine first-trimester medical abortion and perceived related barriers. Descriptive statistics were analyzed using R software. Results: Among 465 respondents, 388 reported providing first-trimester medical abortion across Canada; 44.0% reported experience using telemedicine for some components of care: 49.3% of primary care clinicians and 28.7% of specialists. Telemedicine was used for initial consultation (86.0%), prescription (82.2%), or follow-up (92.2%). The median percentage of telemedicine providers' patients who underwent a dating ultrasound was 90.0. The majority usually followed up with patients through quantitative human chorionic gonadotropin (hCG) (84.2%). Seventy-eight percent perceived barriers to telemedicine; the most common being inability to confirm gestational age with ultrasound (43.0%), and lack of provincial telemedicine abortion fee code to pay practitioners (30.2%), timely access to serum hCG testing (24.6%), and nearby emergency services (23.3%). Discussion: In 2019, fewer than half of respondents reported providing some aspects of first-trimester medical abortion through telemedicine and the majority perceived barriers. Our results can inform knowledge translation activities to reduce barriers and increase telemedicine abortion care in Canada.

Background: This study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results., Methods: We conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON&#95;Marg). ON&#95;Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON&#95;Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant's sex in the analysis., Results: Among the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18-1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82-0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD., Conclusion: Higher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD., (© 2023. The Author(s).)

Background: Adults with low incomes have lower diet quality than their higher income counterparts. In Canada, the British Columbia Farmers' Market Nutrition Coupon Program (FMNCP) provides coupons to low-income households to purchase healthy foods in farmers' markets., Objective: The objective of this study was to examine the impact of the FMNCP on the diet quality of adults with low incomes., Method: In a pragmatic randomized controlled trial conducted in 2019, adults with low incomes (≥18 y) were randomly assigned either to an FMNCP intervention (n = 143) or a no-intervention control group (n = 142). The FMNCP group received 16 coupon sheets valued at $21 per sheet over 10-15 wk to purchase healthy foods from farmers' markets. Participants completed a questionnaire and 2 24-h dietary recalls at baseline (0 wk), immediately post-intervention (10-15 wk), and 16-wk post-intervention (26-31 wk). Diet quality was calculated using the Healthy Eating Index-2015 (HEI-2015). Linear mixed-effects regression assessed differences in HEI-2015 total (primary outcome) and component scores (secondary outcomes) between the FMNCP and control groups at post-intervention and 16-wk post-intervention. Subgroup analyses examined program impacts by sex and age group (18-59 y, ≥60 y)., Results: There were no significant differences in HEI-2015 total scores between the FMNCP and control groups at post-intervention (-0.07; 95% CI: -4.07, 3.93) or 16-wk post-intervention (1.22; 95% CI: -3.00, 5.44) overall or between subgroups. There were no significant between-group differences in HEI-2015 component scores at post-intervention, although there were significant differences in component scores for dairy and fatty acids at 16-wk post-intervention., Conclusion: The FMNCP did not significantly improve diet quality among adults with low incomes over the study period. Further research is needed to explore whether higher subsidy amounts or a longer intervention period is needed to meaningfully improve diet quality among adults with low incomes. This trial was registered at [clinicaltrials.gov] as [NCT03952338]., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Substantial changes in abortion care regulations, available medications and national clinical practice guidelines have occurred since a 2012 national Canadian Abortion Provider Survey (CAPS). We developed and piloted the CAPS 2019 survey instrument to explore changes of the abortion provider workforce, their clinical care as well as experiences with stigma and harassment., Methods: We undertook development and piloting in three phases: (1) development of the preliminary survey sections and questions based on the 2012 survey instrument, (2) content validation and feasibility of including certain content aspects via a modified Delphi Method with panels of clinical and research experts, and (3) pilot testing of the draft survey for face validity and clarity of language; assessing usability of the web-based Research Electronic Data Capture platform including the feasibility of complex skip pattern functionality. We performed content analysis of phase 2 results and used a general inductive approach to identify necessary survey modifications., Results: In phase 1, we generated a survey draft that reflected the changes in Canadian abortion care regulations and guidelines and included questions for clinicians and administrators providing first and second trimester surgical and medical abortion. In phase 2, we held 6 expert panel meetings of 5-8 participants each representing clinicians, administrators and researchers to provide feedback on the initial survey draft. Due to the complexity of certain identified aspects, such as interdisciplinary collaboration and interprovincial care delivery differences, we revised the survey sections through an iterative process of meetings and revisions until we reached consensus on constructs and questions to include versus exclude for not being feasible. In phase 3, we made minor revisions based on pilot testing of the bilingual, web-based survey among additional experts chosen to be widely representative of the study population. Demonstrating its feasibility, we included complex branching and skip pattern logic so each respondent only viewed applicable questions based on their prior responses., Conclusions: We developed and piloted the CAPS 2019 survey instrument suitable to explore characteristics of a complex multidisciplinary workforce, their care and experience with stigma on a national level, and that can be adapted to other countries., (© 2023. The Author(s).)

Background: The 2021 World Health Organization study on the impact of COVID-19 on older people (≥60 years) in the African region highlighted the difficulties they faced as the virus spread across borders and dominated the way of life. These difficulties included disruptions to both essential health care services and social support, as well as disconnections from family and friends. Among those who contracted COVID-19, the risks of severe illness, complications, and mortality were highest among near-old and older persons., Objective: Recognizing that older persons are a diverse group including younger- and older-aged individuals, a study was conducted to track the epidemic among near-old (50-59 years) and older persons (≥60 years) in South Africa covering the 2 years since the epidemic emerged., Methods: Using a quantitative secondary research approach, data for near-old and older persons were extracted for comparative purposes. COVID-19 surveillance outcomes (confirmed cases, hospitalizations, and deaths) and vaccination data were compiled up to March 5th, 2022. COVID-19 surveillance outcomes were plotted by epidemiological week and epidemic waves to visualize the overall growth and trajectory of the epidemic. Means for each age-group and by COVID-19 waves, together with age-specific rates, were calculated., Results: Average numbers of new COVID-19 confirmed cases and hospitalizations were highest among people aged 50-59- and 60-69-years. However, average age-specific infection rates showed that people aged 50-59 years and ≥80 years were most vulnerable to contracting COVID-19. Age-specific hospitalization and death rates increased, with people aged ≥ 70 years most affected. The number of people vaccinated was slightly higher among people aged 50-59 years before Wave Three and during Wave Four, but higher among people aged ≥ 60 years during Wave Three. The findings suggest that uptake of vaccinations stagnated prior to and during Wave Four for both age groups., Discussion: Health promotion messages and COVID-19 epidemiological surveillance and monitoring are still needed, particularly for older persons living in congregate residential and care facilities. Prompt health-seeking should be encouraged, including testing and diagnosis as well as taking up vaccines and boosters, particularly for high-risk older persons., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdelatif, Naidoo, Dunn, Mazinu, Essack, Groenewald, Maharaj, Msomi, Reddy, Roberts and Zuma.)

Introduction The COVID-19 pandemic presented unpredicted challenges to Emergency Medicine (EM) education. The rapid onset of the pandemic created clinical, operational, administrative, and home-life challenges for virtually every member of the medical education community, demanding an educational and professional response at all levels including undergraduate medical education (UME), graduate medical education (GME), and faculty. The Council of Residency Directors in Emergency Medicine (CORD) COVID-19 Educational Impact Task Force was established in 2021 to examine these effects and the response of the EM educational community. Methods The Task Force utilized consensus methodology to develop the survey instruments, which were revised using a modified Delphi process. Both open- and closed-answer questions were included in the survey, which was initially distributed electronically to attendees of the 2021 Virtual Academic Assembly. Results were analyzed quantitatively and qualitatively. Results Sixty-three individuals responded to the first part of the survey (which addressed issues related to UME and GME) and 41 individuals responded to the second part of the survey (which addressed faculty and wellness). The pandemic's influence on EM education was viewed in both a positive and negative light. The transition to virtual platforms had various impacts, including innovation and engagement via technology. Remote technology improved participation in didactics and allowed individuals to more easily participate in departmental meetings. However, this also led to a decreased sense of connection with peers and colleagues resulting in a mixed picture for overall engagement and effectiveness. The Task Force has developed a list of recommendations for best practices for EM programs and for EM organizations. Conclusion The survey results articulated the educational benefits and challenges faced by EM educators during the COVID-19 pandemic. Through the challenging times of the pandemic, many institutional and program-based innovations were developed and implemented to address the new educational environment. These approaches will provide invaluable educational tools for future training. This will also prepare the EM academic community to respond to future educational disruptions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dunn et al.)

Background: The 2021 Wolfson Economics Prize asked how new hospitals should be designed to radically improve patient experiences, clinical outcomes, staff wellbeing and integration with wider health and social care. With a major programme to rebuild and renew hospitals in England underway, the Prize offered an opportunity to understand current thinking about hospitals and their future place., Methods: The 41 submissions that were identified as 'most promising' were reviewed and subjected to framework analysis. Emerging themes were identified and discussed iteratively., Results: Five dominant themes were identified: a calming environment; systems of care; distribution of services; use of technology; and going green. Several tensions and trade-offs were evident across the submissions and a number of gaps were identified in the knowledge base that need to be remedied to ensure that new hospitals are safe and efficient., Conclusion: The previous approach to building new hospitals, with its over-riding drive to reduce costs, has not served the UK well. New ways of thinking about hospital building and design are urgently needed, especially the funding of research and the creation of a national repository devoted to design solutions and post-build evaluations of new hospitals., (© Royal College of Physicians 2023. All rights reserved.)

Acinetobacter are generally soil-dwelling organisms that can also cause serious human infections. A. baumannii is one of the most common causative agents of Acinetobacter infections and is often multidrug resistant. However, an additional 25 species within the genus have also been associated with infection. A. baumannii encodes six resistance nodulation division (RND) efflux pumps, the most clinically relevant class of efflux pumps for antibiotic export, but the distribution and types of RND efflux pumps across the genus is currently unknown. Sixty-four species making up the genus Acinetobacter were searched for RND systems within their genomes. We also developed a novel method using conserved RND residues to predict the total number of RND proteins including currently undescribed RND pump proteins. The total number of RND proteins differed both within a species and across the genus. Species associated with infection tended to encode more pumps. AdeIJK/AdeXYZ was found in all searched species of Acinetobacter, and through genomic, structural and phenotypic work we show that these genes are actually homologues of the same system. This interpretation is further supported by structural analysis of the potential drug-binding determinants of the associated RND-transporters, which reveal their close similarity to each other, and distinctiveness from other RND-pumps in Acinetobacter , such as AdeB. Therefore, we conclude that AdeIJK is the fundamental RND system for species in the genus Acinetobacter . AdeIJK can export a broad range of antibiotics and provides crucial functions within the cell, for example lipid modulation of the cell membrane, and therefore it is likely that all Acinetobacter require AdeIJK for survival and homeostasis. In contrast, additional RND systems, such as AdeABC and AdeFGH, were only found in a subset of Acinetobacter that are associated with infection. By understanding the roles and mechanisms of RND efflux systems in Acinetobacter , treatments for infections can avoid efflux-mediated resistance and improve patient outcomes.

The global COVID-19 pandemic ignited an unprecedented race to develop vaccines and antibody therapeutics. AstraZeneca's pursuit to provide AZD7442 (EVUSHELD), two long-acting, SARS-CoV-2 spike receptor binding domain-specific neutralizing monoclonal antibodies, to individuals at risk on highly accelerated timelines challenged our traditional ways of process development and spurred the rapid adoption of novel approaches. Conventional upstream development processes were replaced by agile strategies that combined technological advances and highly accelerated workflows. With calculated business risks and close cross-functional collaborations, this process paved the way for hyper accelerated antibody development from discovery through manufacturing, process validation, emergency use authorization filing, and global regulatory approvals. The result was initiation of commercial manufacturing at a contract manufacturing organization less than 6 months from the selection of cilgavimab and tixagevimab-a process that historically has taken close to 10 years., (© 2023 Wiley Periodicals LLC.)

Objective: To assess whether antenatal decisions regarding the neonatal care at birth for extremely preterm infants are more likely to be made when using shared decision-making (SDM)-style consultations compared to standard consultations., Study Design: In 2015, we implemented a clinical practice guideline promoting SDM use within antenatal consultations in our single-centre university-based perinatal unit. We conducted a prospective cohort study with a retrospective chart review based on data collected from all pregnant women presenting to obstetrical triage between 22 + 0 and 25 + 6 weeks gestation between September 2015 and June 2018., Result: Two-hundred-and-seventeen cases presented; 137 received antenatal consultations with 82 (60%) being SDM-style. Decisions were frequently made (88%; 120/137) after the consultations, with no significant difference between consultation style (RR 1.08, 95% CI [0.95-1.26], p = 0.28)., Conclusion: The provision of either an SDM-style or a standard antenatal consultation seemed to comparably facilitate the reaching of a care decision., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The COVID-19 pandemic has significant impact on long-term care (LTC) residents' health and well-being., Objectives: This study investigated resident experiences of loneliness during the COVID-19 pandemic in Canadian LTC homes to offer lessons learned and implications., Methods: 15 residents and 16 staff members were recruited from two large urban Canadian LTC homes with large outbreaks and fatalities. We used a telepresence robot to conduct one-on-one semi-structured interviews with participants remotely. We applied the Collaborative Action Research (CAR) methodology and report the early phase of CAR focused on collecting data and reporting findings to inform actions for change. Thematic analysis was performed to identify themes., Results: Four themes were identified. The first two themes characterise what commonly generated feelings of loneliness amongst residents, including (1) social isolation and missing their family and friends and (2) feeling hopeless and grieving for lives lost. The second two themes describe what helped residents alleviate loneliness, including (3) social support and (4) creating opportunities for recreation and promoting positivity., Conclusions: Residents living in LTC experienced significant social isolation and grief during the pandemic that resulted in loneliness and other negative health consequences., Implications for Practice: Promoting meaningful connection, safe recreational activities and a positive atmosphere in LTC homes during the pandemic may help mitigate residents' experiences of loneliness due to social isolation and/or grief and enhance their quality of life., (© 2022 The Authors. International Journal of Older People Nursing published by John Wiley & Sons Ltd.)

Introns are included in genes encoding therapeutic proteins for their well-documented function of boosting expression. However, mis-splicing of introns in recombinant immunoglobulin (IgG) heavy chain (HC) transcripts can produce amino acid sequence product variants. These variants can affect product quality; therefore, purification process optimization may be needed to remove them, or if they cannot be removed, then in-depth characterization must be carried out to understand their effects on biological activity. In this study, HC transgene engineering approaches were investigated and were successful in significantly reducing the previously identified IgG HC splice variants to <0.5%. Subsequently, a comprehensive evaluation was conducted to understand the influence of the different introns in the HC genes on the expression of recombinant biotherapeutic antibodies. The data revealed an unexpected cooperation between specific introns for efficient splicing, where intron retention led to significant reductions in IgG expression of up to 75% for some intron combinations. Furthermore, it was shown that HC introns could be fully removed without significantly affecting productivity. This work paves the way for future biotherapeutic antibody transgene design with regard to inclusion of HC introns. By removing unnecessary introns, transgene mRNA transcript will no longer be mis-spliced, thereby eliminating HC splice variants and improving antibody product quality.