Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors.

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data from 31 human colorectal specimens enabled phylogeographic mapping of tumor evolution that revealed individualized progression trajectories and accompanying microenvironmental and clonal alterations. Phylogeographic mapping ordered genetic events, classified tumors by their evolutionary dynamics, and placed clonal regions along global pseudotemporal progression trajectories encompassing the chromosomal instability (CIN+) and hypermutated (HM) pathways. Integrated single-cell and spatial transcriptomic data revealed recurring epithelial programs and infiltrating immune states along progression pseudotime. We discovered an immune exclusion signature (IEX), consisting of extracellular matrix regulators DDR1, TGFBI, PAK4, and DPEP1, that charts with CIN+ tumor progression, is associated with reduced cytotoxic cell infiltration, and shows prognostic value in independent cohorts. This spatial multi-omic atlas provides insights into colorectal tumor-microenvironment co-evolution, serving as a resource for stratification and targeted treatments.

Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps.

Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC.

Geography is more important than life history in the recent diversification of the tiger salamander complex.

The North American tiger salamander species complex, including its best-known species, the Mexican axolotl, has long been a source of biological fascination. The complex exhibits a wide range of variation in developmental life history strategies, including populations and individuals that undergo metamorphosis; those able to forego metamorphosis and retain a larval, aquatic lifestyle (i.e., paedomorphosis); and those that do both. The evolution of a paedomorphic life history state is thought to lead to increased population genetic differentiation and ultimately reproductive isolation and speciation, but the degree to which it has shaped population- and species-level divergence is poorly understood. Using a large multilocus dataset from hundreds of samples across North America, we identified genetic clusters across the geographic range of the tiger salamander complex. These clusters often contain a mixture of paedomorphic and metamorphic taxa, indicating that geographic isolation has played a larger role in lineage divergence than paedomorphosis in this system. This conclusion is bolstered by geography-informed analyses indicating no effect of life history strategy on population genetic differentiation and by model-based population genetic analyses demonstrating gene flow between adjacent metamorphic and paedomorphic populations. This fine-scale genetic perspective on life history variation establishes a framework for understanding how plasticity, local adaptation, and gene flow contribute to lineage divergence. Many members of the tiger salamander complex are endangered, and the Mexican axolotl is an important model system in regenerative and biomedical research. Our results chart a course for more informed use of these taxa in experimental, ecological, and conservation research.

People with Intellectual Disabilities, Dysphagia and Post-Covid Syndrome.

People with Intellectual Disability (ID) were more likely to contract COVID-19 infection and more likely to die from the consequences. However, there is no evidence on the long-term impact of COVID-19 infection in people with ID. Post-Covid Syndrome (PCS) is an established diagnosis that requires specialist clinical support. To date there is no data on how common PCS is in people with ID, or how symptoms present. Dysphagia is identified as a clinical marker because of the known association with PCS, and the clear objective diagnostic criteria applicable through specialist assessment. This investigation presents a cohort of people with ID, who developed dysphagia/worsening of dysphagia post diagnosis with COVID-19. Cases were identified through support from the Royal College of Speech and Language Therapists. Data was collected by electronic survey, including application of the COVID-19 Yorkshire Rehabilitation Scale-modified (C19-YRSm). The C19-YRSm is a validated assessment tool for PCS and it's impact upon functional disability. This case series identifies that symptoms consistent with PCS are present in people with ID, post-COVID-19 infection. The risk of diagnostic overshadowing or misdiagnosis is high due to the subjective nature and the quality of PCS symptoms. People with ID who develop PCS may not be readily identified by clinical services and therefore not be accessing the specialist medical support required. Furthermore, changes in behaviour secondary to PCS may lead to unnecessary increased prescribing of psychotropic medication which in itself risks worsening dysphagia. Dysphagia could be an important bellwether to identify PCS in people with ID.

Hospital-acquired pressure injury prevention in people with a BMI of 30.0 or higher: A scoping review.

AIM(S): To: (1) explore current best practices for hospital-acquired pressure injury prevention in high BMI patients; (2) summarize nurses' experiences in preventing and managing them; (3) explore the association between a high BMI and occurrence and severity of pressure injury. DESIGN: Exploratory. METHODS: Scoping review. DATA SOURCES: Ovid MEDLINE, EBSCO CINAHL Plus, JBI Evidence Synthesis, Scopus, Embase, clinical registries and grey literature (search dates: January 2009 to May 2021). RESULTS: Overall, 1479 studies were screened. The included studies were published between 2010 and 2022. Five interventional studies and 32 best practice recommendations (Objective 1) reported low-quality evidence. Findings of thematic analysis reported in nine studies (Objective 2) identified nurses' issues as insufficient bariatric equipment, inadequate staffing, weight bias, fatigue, obese-related terminology issues, ethical dilemmas and insufficient staff education in high BMI patients' pressure injury prevention. No association between hospital-acquired pressure injury occurrence and high BMI were reported by 18 out of 28 included studies (Objective 3). CONCLUSION: Quality of evidence was low for the interventional studies and best practice recommendations. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Current (2019) International Pressure Injury Guideline to be used despite the low quality of evidence of most best practice recommendations. IMPACT STATEMENT: This study addressed hospital-acquired pressure injury prevention in high BMI patients. Greater proportion of studies in this review found no association between high BMI and occurrence of hospital-acquired pressure injury. Nurses need educational interventions on pressure injury prevention in high body mass index people, sufficient staffing for repositioning and improved availability of bariatric equipment. REPORTING METHOD: We adhered to relevant EQUATOR guidelines, PRISMA extension for scoping reviews. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Larger clinical trials are needed on repositioning frequency, support surfaces, prophylactic dressings and risk assessment tools to inform clinical practice guidelines on pressure injury prevention in high BMI people. PROTOCOL REGISTRATION: Wound Practice and Research (https://doi.org/10.33235/wpr.29.3.133-139).

Nurses' experiences of hospital-acquired pressure injury prevention in acute healthcare services in Victoria, Australia: A qualitative study using the Theoretical Domains Framework.

We investigated nurses' experiences of hospital-acquired pressure injury (PI) prevention in acute care services to better understand how PI prevention may be optimised. We used the Theoretical Domains Framework to systematically identify barriers and enablers to evidence-based preventive practices as required by the International Guideline. This study was one element of a complex capacity building project on PI surveillance and prevention within the acute health service partners of Monash Partners Academic Health Science Centre, an accredited academic health partnership located in Melbourne, Australia. We adopted a qualitative descriptive design. We interviewed 32 nurses that provided care in intensive care units, general wards and COVID wards of four acute care services. Nurses were recruited from four large acute care services (three public, one private) located in Melbourne. Most of them worked with patients who were at high risk of hospital-acquired PI on a daily basis. Interview transcripts were coded and analysed using thematic analysis guided by the Theoretical Domains Framework. The domains referred to most frequently by all participants included: Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, and Environmental Context and Resources. The key barriers discussed by nurses included gaps in nurses' knowledge and skills related to identification and staging of PI, heavy nursing workload and inadequate staffing levels, stigma and self-blame related to PI identification, and exacerbating impacts of the COVID-19 pandemic. Main facilitators discussed were training programmes, nursing audits and feedback, and teamwork. Participants suggested improvements including accessible and tailored training, visual reminders, and addressing heavy workloads and emotional barriers nurses face. Investing in tailored training initiatives to improve nurses' knowledge and organisational changes to address low level staffing and heavy workloads are urgently needed to support nurses in delivering optimal care and preventing hospital-acquired PI.

'People need to know we exist!': an exploratory study of the labour experiences of transmasculine and non-binary sex workers and implications for harm reduction.

This article presents findings demonstrating that transmasculine and non-binary people work in sex industries worldwide. Informed by results from a qualitative study with transmasculine and non-binary sex workers, it provides much-needed demographic information about this population, their clients and workers' safety concerns. It explores the importance of using an intersectional framework and inclusive methods to gather demographic data regarding gender and sexuality in studies of sex work. Not only is an intersectional framework necessary for empirical studies of sex work, but it is also vital to developing successful harm reduction strategies. Using an intersectional frame in studies of sex work and harm reduction can provide much-needed insight into the development of inclusive services and programmes that help the most marginal. So long as researchers, social service agencies and health providers treat transmasculine and non-binary providers as non-existent, this reduces their ability to meet the needs of all sex workers.

Characteristics of Sports-Related Injuries Presenting to a Pediatric Emergency Department.

OBJECTIVE: Pediatric injuries associated with participation in sports are common. Understanding the epidemiology and trends of sports-related injuries is an important component of injury prevention efforts and is the objective of this study. METHODS: A retrospective review of sports injuries presenting during the course of 1 year (2019) to the emergency department (ED) of Benjamin Russell Hospital for Children, a large academic children's hospital, was performed. Inclusion criteria focused on patients 18 years old and younger whose ED visit resulted from active participation in a sport. Cases were identified using International Classification of Diseases, Tenth Revision codes. Demographic data were collected and included sex, age, race, injury specifics (sport, location, type, and mechanism). Descriptive statistics were performed and categorical variables were analyzed using the χ2 test. RESULTS: A total of 1333 injuries seen by the ED during 2019 were sports injuries. Most commonly, these injuries were associated with football (43%), basketball (36%), soccer (11%), or baseball (8%). Considering sports-related injuries, 428 (32%) patients were 12 years and younger and 905 (68%) were 12 years old and older. The median age was 13 years (interquartile range 4 years). Other demographic findings included male sex 1143/1333 (86%) and Black race 835/1333 (63%). School was the most common location for sports injuries (28%). When comparing injuries by age groups (younger than 12 vs 12 and older), football and baseball injuries were more common in those younger than 12 years (53% vs 38%, z = 5.2, P < 0.00001; and 14.0% vs. 5.6%, z = 4.9, P < 0.00001, respectively), whereas basketball and soccer injuries were more common in those 12 years and older (43% vs 22%, z = 7.4, P < 0.00001; and 11.4% vs 9.3%, z = 5.9, P < 0.00001, respectively). When comparing injuries by sex, football and baseball injuries were more common in males (49% vs 6%, z = 11.1, P < 0.00001; and 9.4% vs. 2.1%, z = 3.3, P < 0.00001, respectively), whereas basketball and soccer injuries were more common in females (59% vs 32%, z = 7.2, P < 0.00001; and 27% vs 8%, z = 7.8, P < 0.00001, respectively. CONCLUSIONS: Sports injuries that are commonly encountered in the ED differ in age and sex. Basketball and soccer injuries were more likely to be encountered in older females, whereas baseball and football injuries were more likely seen in younger males. This may reflect efforts that have been previously focused on the sports considered to be higher risk, especially for concussive injuries. This information can help guide future preventive efforts provided by primary physicians, schools, and coaches.

Social, demographic and behavioural determinants of SARS-CoV-2 infection: a case-control study carried out during mass community testing of asymptomatic individuals in South Wales, December 2020.

Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43-8.03), social care (aOR 2.63, 1.22-5.67) or healthcare (aOR 2.31, 1.29-4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03-4.62), visit a pub (aOR 2.87, 1.11-7.37) and smoke or vape (aOR 1.54, 1.02-2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.

Cost-effectiveness of a whole-area testing pilot of asymptomatic SARS-CoV-2 infections with lateral flow devices: a modelling and economic analysis study.

BACKGROUND: Mass community testing for SARS-CoV-2 by lateral flow devices (LFDs) aims to reduce prevalence in the community. However its effectiveness as a public heath intervention is disputed. METHOD: Data from a mass testing pilot in the Borough of Merthyr Tydfil in late 2020 was used to model cases, hospitalisations, ICU admissions and deaths prevented. Further economic analysis with a healthcare perspective assessed cost-effectiveness in terms of healthcare costs avoided and QALYs gained. RESULTS: An initial conservative estimate of 360 (95% CI: 311-418) cases were prevented by the mass testing, representing a would-be reduction of 11% of all cases diagnosed in Merthyr Tydfil residents during the same period. Modelling healthcare burden estimates that 24 (16-36) hospitalizations, 5 (3-6) ICU admissions and 15 (11-20) deaths were prevented, representing 6.37%, 11.1% and 8.2%, respectively of the actual counts during the same period. A less conservative, best-case scenario predicts 2333 (1764-3115) cases prevented, representing 80% reduction in would-be cases. Cost -effectiveness analysis indicates 108 (80-143) QALYs gained, an incremental cost-effectiveness ratio of £2,143 (£860-£4,175) per QALY gained and net monetary benefit of £6.2 m (£4.5 m-£8.4 m). In the best-case scenario, this increases to £15.9 m (£12.3 m-£20.5 m). CONCLUSIONS: A non-negligible number of cases, hospitalisations and deaths were prevented by the mass testing pilot. Considering QALYs gained and healthcare costs avoided, the pilot was cost-effective. These findings suggest mass testing with LFDs in areas of high prevalence (> 2%) is likely to provide significant public health benefit. It is not yet clear whether similar benefits will be obtained in low prevalence settings or with vaccination rollout.

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

CRISPR/Cas9-targeted removal of unwanted sequences from small-RNA sequencing libraries.

In small RNA (smRNA) sequencing studies, highly abundant molecules such as adapter dimer products and tissue-specific microRNAs (miRNAs) inhibit accurate quantification of lowly expressed species. We previously developed a method to selectively deplete highly abundant miRNAs. However, this method does not deplete adapter dimer ligation products that, unless removed by gel-separation, comprise most of the library. Here, we have adapted and modified recently described methods for CRISPR/Cas9-based Depletion of Abundant Species by Hybridization ('DASH') to smRNA-seq, which we have termed miRNA and Adapter Dimer-DASH (MAD-DASH). In MAD-DASH, Cas9 is complexed with single guide RNAs (sgRNAs) targeting adapter dimer ligation products, alongside highly expressed tissue-specific smRNAs, for cleavage in vitro. This process dramatically reduces adapter dimer and targeted smRNA sequences, can be multiplexed, shows minimal off-target effects, improves the quantification of lowly expressed miRNAs from human plasma and tissue derived RNA, and obviates the need for gel-separation, greatly increasing sample throughput. Additionally, the method is fully customizable to other smRNA-seq preparation methods. Like depletion of ribosomal RNA for mRNA-seq and mitochondrial DNA for ATAC-seq, our method allows for greater proportional read-depth of non-targeted sequences.

Evaluation of a drop-in waste volume reduction method for liquid investigation derived waste containing per- and polyfluoroalkyl substances.

Development of on-site treatment strategies for PFAS-containing investigation derived waste (IDW) will decrease the potential for secondary release following off-site disposal, lower disposal costs, and promote more effective long-term management of PFAS-laden waste. Herein, we report the application of a simple, drop-in treatment that utilizes one of two PFAS sorbents: bituminous granular activated carbon (GAC) or strong base anion exchange resin (IX) and a small circulation pump to adsorb and concentrate PFAS impacted mass from liquid IDW collected from two sites with disparate water chemistries and synthetic IDW amended with PFAS-containing aqueous film forming foam (AFFF). Bench scale intermittent circulation experiments revealed that bituminous granular activated carbon (GAC, 0.5 mg/mL) removed up to 97.0 ± 1.4% and 96.4 ± 0.5% of PFOS and PFOA, respectively, in both site-derived IDW sources. Improved performance was observed in experimental treatments containing a strong base anion exchange resin (IX, 0.5 mg/mL), where up to 99.4 ± 0.1% and 96.7 ± 0.2% of PFOS and PFOA were removed, respectively. High chloride concentrations (20 g/L) reduced removal of short chain perfluorocarboxylates (PFBA and PFHxA) using GAC or IX, but high salt concentrations had negligible effects on the removal of PFOA, PFBS, PFHxS, or PFOS. Excellent scalability was observed in mesoscale experiments, where the majority of amended PFAS mass was removed from synthetic IDW within five days of vessel circulation using two different PFAS-capture configurations. Combined PFOS and PFOA concentrations were reduced to levels below 0.07 µg/L using either GAC or IX for both configurations. Results generated in this study support the application of this approach as an economical strategy for potential waste volume reduction in IDW destined for off-site disposal.

Reversible deficits in apical transporter trafficking associated with deficiency in diacylglycerol acyltransferase.

Deficiency in diacylglycerol acyltransferase (DGAT1) is a rare cause of neonatal diarrhea, without a known mechanism or in vitro model. A patient presenting at our institution at 7 weeks of life with failure to thrive and diarrhea was found by whole-exome sequencing to have a homozygous DGAT1 truncation mutation. Duodenal biopsies showed loss of DGAT1 and deficits in apical membrane transporters and junctional proteins in enterocytes. When placed on a very low-fat diet, the patient's diarrhea resolved with normalization of brush border transporter localization in endoscopic biopsies. DGAT1 knockdown in Caco2-BBe cells modeled the deficits in apical trafficking, with loss of apical DPPIV and junctional occludin. Elevation in cellular lipid levels, including diacylglycerol (DAG) and phospholipid metabolites of DAG, was documented by lipid analysis in DGAT1 knockdown cells. Culture of the DGAT1 knockdown cells in lipid-depleted media led to re-establishment of occludin and return of apical DPPIV. DGAT1 loss appears to elicit global changes in enterocyte polarized trafficking that could account for deficits in absorption seen in the patient. The in vitro modeling of this disease should allow for investigation of possible therapeutic targets.

Dual indexed library design enables compatibility of in-Drop single-cell RNA-sequencing with exAMP chemistry sequencing platforms.

BACKGROUND: The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number of experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, such as the Illumina NovaSeq 6000, enables this demand to be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer sequencing technologies, such as index-hopping, and their ability to generate high quality data has yet to be systematically evaluated. RESULTS: Here, we engineered a dual-indexed library structure, called TruDrop, on top of the inDrop scRNA-seq platform to solve these compatibility challenges, such that TruDrop libraries and standard Illumina libraries can be sequenced alongside each other on the NovaSeq. On scRNA-seq libraries, we implemented a previously-documented countermeasure to the well-described problem of index-hopping, demonstrated significant improvements in base-calling accuracy on the NovaSeq, and provided an example of multiplexing twenty-four scRNA-seq libraries simultaneously. We showed favorable comparisons in transcriptional diversity of TruDrop compared with prior inDrop libraries. CONCLUSIONS: Our approach enables cost-effective, high throughput generation of sequencing data with high quality, which should enable more routine use of scRNA-seq technologies.

Leaders' perspectives on learning health systems: a qualitative study.

BACKGROUND: Integrated utilisation of digital health data has the power to transform healthcare to deliver more efficient and effective services, and the learning health system (LHS) is emerging as a model to achieve this. The LHS uses routine data from service delivery and patient care to generate knowledge to continuously improve healthcare. The aim of this project was to explore key features of a successful and sustainable LHS to inform implementation in an Academic Health Science Centre context. METHODS: We purposively identified and conducted semi-structured qualitative interviews with leaders, experienced in supporting or developing data driven innovations in healthcare. A thematic analysis using NVivo was undertaken. RESULTS: Analysis of 26 interviews revealed five themes thought to be integral in an effective, sustainable LHS: (1) Systematic approaches and iterative, continuous learning with implementation into healthcare contributing to new best-practice care; (2) Broad stakeholder, clinician and academic engagement, with collective vision, leadership, governance and a culture of trust, transparency and co-design; (3) Skilled workforce, capability and capacity building; (4) Resources with sustained investment over time and; (5) Data access, systems and processes being integral to a sustainable LHS. CONCLUSIONS: This qualitative study provides insights into the elements of a sustainable LHS across a range of leaders in data-driven healthcare improvement. Fundamentally, an LHS requires continuous learning with implementation of new evidence back into frontline care to improve outcomes. Structure, governance, trust, culture, vision and leadership were all seen as important along with a skilled workforce and sustained investment. Processes and systems to optimise access to quality data were also seen as vital in an effective, sustainable LHS. These findings will inform a co-designed framework for implementing a sustainable LHS within the Australian healthcare and Academic Health Science Centre context. It is anticipated that application of these findings will assist to embed and accelerate the use of routine health data to continuously generate new knowledge and ongoing improvement in healthcare delivery and health outcomes.

The feasibility of a multi-professional training to improve how health care professionals deliver different news to families during pregnancy and at birth.

BACKGROUND: In the United Kingdom, pregnant women are offered foetal anomaly screening to assess the chance of their baby being born with eleven different conditions. How health care professionals (HCPs) deliver news about a child having a congenital anomaly affects how it is received and processed by parents. We refer to this news as different news. METHODS: We conducted a mixed methods evaluation of a training intervention to improve how HCPs deliver different news. Twenty-six HCPs self-completed pretraining and posttraining questionnaires on skills, knowledge, and attitudes related to delivering different news. Qualitative interviews were conducted with eight HCPs. Quantitative data were analysed using descriptive statistics, the paired t test to compare the pre and post scores and estimate the difference between pre and post scores, and the 95% confidence interval. Qualitative data were analysed using framework analysis guided by the Theoretical Domains Framework (TDF). RESULTS: The training intervention was both feasible and acceptable. HCPs indicated that it enhanced or consolidated their knowledge and skills, covered topics relevant to their practice, and that they would recommend it to colleagues. Participants particularly valued integration of the voice of parents with lived experience in the training. Significant increase in mean scores were observed in confidence to deliver different news (2.81, 95% CI [2.43, 3.19] to 4.28, 95% CI [4.09, 4.47]; p < .001) and skills to deliver different news (3.00, 95% CI [2.64, 3.36] to 4.36, 95% CI [4.13, 4.59]; p < .001). HCPs reported feeling more confident in their ability to provide sensitive, responsive, balanced care to families. CONCLUSIONS: The significant improvements in confidence and skills reported by HCPs suggest that the training may be effective in equipping HCPs to minimize the distress, anxiety, and depression associated with receiving different news. This represents a key aspect of the prevention of mental ill health across the life course.

Patient education materials on pressure injury prevention in hospitals and health services in Victoria, Australia: Availability and content analysis.

Pressure injuries (PIs) are a common quality indicator for hospital care, and preventing PIs often requires patient engagement; as such, Australian consensus research has recommended that high-quality education materials be made to patients for PIs via hospital networks. The purpose of the present study was to assess the availability and accuracy of patient education materials on PIs in publicly available hospital websites in Victoria, Australia. Two independent coders assessed 212 websites for content on PI prevention and management, analysing availability and accuracy of PI definitions, risk factors, preventive strategies, referral, visual tools, consumer endorsement, information for family/carers, and translation on community languages. A greater proportion of hospitals did not have any patient education materials on PI prevention publicly available, with private hospitals (compared with public) and metropolitan hospitals (compared to rural) more likely to have materials available on their sites. The available materials contained accurate messages on PI defining characteristics and risk factors for PIs, although there was considerable variability on the availability of other information. Our findings suggest a significant deficit in the availability of educational materials for acute care patients and their families. There is a need for evidence-based, consumer-endorsed, uniform materials on all hospital websites to prevent PIs in acute care.

Improving juror sensitivity to specific eyewitness factors: judicial instructions fail the test.

A recent New Jersey Supreme Court decision recognized the difficulty jurors have with evaluating eyewitness evidence. This decision resulted in the development of instructions that highlight factors affecting identification accuracy. Research has explored the efficacy of eyewitness instructions for improving jurors' decision-making. Jurors in these studies are typically presented with identifications that manipulate multiple witnessing and identification conditions simultaneously, making it difficult to ascertain whether instructions help jurors evaluate any one eyewitness factor. We conducted two experiments to examine how jurors evaluate eight individual eyewitness factors with and without instructions. Across both experiments, none of the individual eyewitness factors nor instructions influenced jurors. Instructions only assisted jurors when multiple eyewitness factors were collapsed to create either extremely good or poor-quality identifications. These findings contribute to the long history of jurors remaining largely insensitive to the nuances of witnessing and identification conditions. Current safeguards may only assist jurors under limited circumstances.

Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.

Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes. Furthermore, these antibody phenotypes were not affected by changes in environmental factors such as the gut microbiota composition. Antigen-specific B cells following immunization had a marked difference in capability to class switch, resulting in perturbed IgG isotype antibody production. In vitro, a B-cell intrinsic defect in the regulation of class-switch recombination was identified in mice with low IgG antibody production. Whole genome sequencing identified polymorphisms associated with the magnitude of antibody produced, and we propose candidate genes that may regulate isotype class-switching capability. This study highlights that mice sourced from different vendors can have significantly altered humoral immune response profiles, and provides a resource to interrogate genetic regulators of antibody responsiveness. Together these results further our understanding of immune heterogeneity and suggest additional research on the genetic influences of adjuvanted vaccine strategies is warranted for enhancing vaccine efficacy.