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The concept of interaction classes (iClasses) for multi-environment trial data was introduced to address the problem of summarising variety performance across environments in the presence of variety by environment interaction (VEI). The approach involves the fitting of a factor analytic linear mixed model (FALMM), with the resultant estimates of factor loadings being used to form groups of environments (iClasses) that discriminate varieties with different patterns of VEI. It is then meaningful to summarise variety performance across environments within iClasses. The iClass methodology was developed with respect to a FALMM in which the genetic effects for different varieties were assumed independent. This was done for pedagogical reasons but it was pointed out that the accuracy of variety selection is greatly enhanced by considering the genetic relatedness of varieties, either via ancestral or genomic information. The focus of the current paper is therefore to extend the iClass approach for FALMMs which incorporate such information. In addition a measure of stability of variety performance across iClasses is defined. The utility of the approach for variety selection is illustrated using a multi-environment trial dataset from the lentil breeding program operated by Agriculture Victoria.
In May 2017, whole-genome sequencing (WGS) became the primary subtyping method for Salmonella in Canada. As a result of the increased discriminatory power provided by WGS, 16 multi-jurisdictional outbreaks of Salmonella associated with frozen raw breaded chicken products were identified between 2017 and 2019. The majority (15/16) were associated with S. enteritidis, while the remaining outbreak was associated with S. Heidelberg. The 16 outbreaks included a total of 487 cases with ages ranging from 0 to 98 years (median: 24 years); 79 hospitalizations and two deaths were reported. Over the course of the outbreak investigations, 14 frozen raw breaded chicken products were recalled, and one was voluntarily withdrawn from the market. After previous changes to labelling and the issuance of public communication for these products proved ineffective at reducing illnesses, new industry requirements were issued in 2019, which required the implementation of measures at the manufacturing/processing level to reduce Salmonella to below detectable amounts in frozen raw breaded chicken products. Since implementation, no further outbreaks of Salmonella associated with frozen breaded chicken have been identified in Canada, a testament to the effectiveness of these risk mitigation measures.
Advances in artificial intelligence (AI) have great potential to help address societal challenges that are both collective in nature and present at national or transnational scale. Pressing challenges in healthcare, finance, infrastructure and sustainability, for instance, might all be productively addressed by leveraging and amplifying AI for national-scale collective intelligence. The development and deployment of this kind of AI faces distinctive challenges, both technical and socio-technical. Here, a research strategy for mobilising inter-disciplinary research to address these challenges is detailed and some of the key issues that must be faced are outlined.
In the past five years, there has been a striking increase in the number of people experiencing homelessness, including unsheltered homelessness, across Canada (Infrastructure Canada, 2024). Facing this growing crisis, local governments are changing and expanding their responses. An important innovation is tiny homes, a form of deeply affordable and supportive housing for people leaving homelessness. In this brief article, I ask what explains local government's increased leadership and innovation with respect to homelessness and housing crises. Drawing on interviews and document analysis regarding the development of a tiny homes community in a mid-sized BC municipality, I identify three factors that have contributed to local government's policy innovation: 1) local officials are keenly aware of the inadequacies of federal and provincial responses and of the need for alternative approaches; 2) they hold important resources, notably local knowledge and land; and 3) they are facing pressure to respond from citizens and service providers.
The field of healthcare epidemiology is increasingly focused on identifying, characterizing, and addressing social determinants of health (SDOH) to address inequities in healthcare quality. To identify evidence gaps, we examined recent systematic reviews examining the association of race, ethnicity, and SDOH with inpatient quality measures.
Methods:
We searched Medline via OVID for English language systematic reviews from 2010 to 2022 addressing race, ethnicity, or SDOH domains and inpatient quality measures in adults using specific topic questions. We imported all citations to Covidence (www.covidence.org, Veritas Health Innovation) and removed duplicates. Two blinded reviewers assessed all articles for inclusion in 2 phases: title/abstract, then full-text review. Discrepancies were resolved by a third reviewer.
Results:
Of 472 systematic reviews identified, 39 were included. Of these, 23 examined all-cause mortality; 6 examined 30-day readmission rates; 4 examined length of stay, 4 examined falls, 2 examined surgical site infections (SSIs) and one review examined risk of venous thromboembolism. The most evaluated SDOH measures were sex (n = 9), income and/or employment status (n = 9), age (n = 6), race and ethnicity (n = 6), and education (n = 5). No systematic reviews assessed medication use errors or healthcare-associated infections. We found very limited assessment of other SDOH measures such as economic stability, neighborhood, and health system access.
Conclusion:
A limited number of systematic reviews have examined the association of race, ethnicity and SDOH measures with inpatient quality measures, and existing reviews highlight wide variability in reporting. Future systematic evaluations of SDOH measures are needed to better understand the relationships with inpatient quality measures.
Our interviews of inpatient clinicians (physicians, physician assistants) modeled after the Capability, Opportunity, and Motivation Model of Behavior model revealed opportunity and motivation as important drivers for overdiagnosis and overprescribing for asymptomatic bacteriuria in older adults. Understanding these barriers is an important step toward implementing age-friendly stewardship interventions.
OBJECTIVES/GOALS: The goal of this study is to develop a multi-centered Translational Studio model that can help in the development of quality translational studies using resources from four different institutional partners (University of Texas Medical Branch, Texas Southern University, University of Houston Clear Lake and Houston Methodist). METHODS/STUDY POPULATION: We conducted two rounds of four Futures Workshops for a total participation of 28 stakeholders from four different partners. Future Workshops were used to critique, envision, and articulate novel “futures” that can be achieved at least partly through design practices (Muller, 2002). In the first round of workshops, we asked participants about their institutions’ strengths, weaknesses, resources and investigator needs regarding the Studio. In the second round we asked about different studio models, pros and cons of each model and guiding principles for a studio. Alongside a pragmatic content analysis, multi-stage deductive and inductive qualitative analyses were used to understand people’s views on the future of a multi-institutional Clinical Trials Studio. RESULTS/ANTICIPATED RESULTS: The first-round workshops’ analysis described peoples’ goals for what the studio should be. The future desired studio was described as guide, matchmaker, initiator and advocate. The second-round workshops’ analysis discussed the pros and cons of a variety of possible models including, centralized, decentralized, and topic-specific (and allowed other suggestions) while also describing principles for the guidance of a studio. Here the analysis showed people wanted certain characteristics for the studio (i.e. effective, efficient, locally-responsive, consistent, etc.). They also prescribed four principles that a studio should be guided by: non-hierarchical partnership, user-centeredness, respect/collegiality, and sharing. DISCUSSION/SIGNIFICANCE: The future workshops were useful in developing a shared multi-institutional Clinical Trials Studio model that is planned to be deployed in 2025. Participants valued a studio that was both directly supportive to participants and played a role in creating or advocating for institutional resources and policy for research.
OBJECTIVES/GOALS: Health care accounts for an estimated 10% of U.S. greenhouse gas (GHG) emissions. Concerted efforts to decrease waste are needed including critical appraisal of single use items. The purpose of this study was to conduct life cycle analyses (LCA) of a pediatric single use laryngoscope to inform environmental impact and identify targets to reduce waste. METHODS/STUDY POPULATION: LCA was used to quantify the environmental impact of a single use pediatric laryngoscope. LCA is an industry standard measure of energy consumption, water consumption, and GHG emissions encompassing a “cradle-to-grave” assessment. The GREET model (Greenhouse gases, Regulated Emissions and Energy use in Technologies) and Open LCA model were used as sources for product/raw material data. Separate analysis was completed for the battery powering the light emitting diode (LED) lights. RESULTS/ANTICIPATED RESULTS: The LCA revealed 598.2 g of CO2 equivalents for the 121g single use pediatric laryngoscope. There were an estimated 26,849 cases that used single use laryngoscope last year at our free-standing children’s hospital resulting in 16.1 metric tons of CO2 equivalents. This is equivalent to 41,273 miles driven by an average gasoline powered vehicle. The 1.5 V battery was the highest contributor to the laryngoscope’s GHG emissions. While the battery has an estimated 2,800 hours of life, single use laryngoscopes are reported in the literature as being used for only an average of 30 seconds to 2 minutes. DISCUSSION/SIGNIFICANCE: Single use laryngoscopes are high contributors to GHGs. Specifically, the batteries contained in the laryngoscopes are wasteful and challenging to remove and recycle. Future efforts to decrease waste in the OR should target use of similar items that have reusable battery components to improve environmental sustainability.
In the UK, the number of patients urgently referred for suspected cancer is increasing, and providers are struggling to cope with demand. We explore the potential cost-effectiveness of a new risk prediction test – the PinPoint test – to triage and prioritize patients urgently referred with suspected urological cancers.
Methods
Two simulation models were developed to reflect the diagnostic pathways for patients with (i) suspected prostate cancer, and (ii) bladder or kidney cancer, comparing the PinPoint test to current practice. An early economic analysis was conducted from a UK National Health Service (NHS) perspective. The primary outcomes were the percentage of individuals seen within 2 weeks and health care costs. An exploratory analysis was conducted to understand the potential impact of the Pinpoint test on quality-adjusted life years gained.
Results
Across both models and applications, the PinPoint test led to more individuals with urological cancer being seen within 2 weeks. Using PinPoint only to prioritize patients led to increased costs overall, whereas using PinPoint to both triage and prioritize patients led to cost savings. The estimated impact on life years gained/lost was very small and highly uncertain.
Conclusions
Using the PinPoint test to prioritize urgent referrals meant that more individuals with urological cancer were seen within 2 weeks, but at additional cost to the NHS. If used as a triage and prioritization tool, the PinPoint test shortens wait times for referred individuals and is cost saving. More data on the impact of short-term delays to diagnosis on health-related quality of life is needed.
Functional connectivity of the default mode network (DMN) during rest has been shown to be different among adults with Mild Cognitive Impairment (MCI) relative to aged-matched individuals without MCI and is predictive of transition to dementia. Post-traumatic stress disorder (PTSD) is also associated with aberrant connectivity of the DMN. Prior work from this group has demonstrated a higher rate of MCI and PTSD among World Trade Center (WTC) responders relative to the general population. The current study sought to investigate the main and interactive effects of MCI and PTSD on DMN functioning. Based on prior work, we hypothesized that MCI, but not PTSD, would predict aberrant connectivity in the DMN.
Participants and Methods:
99 WTC responders aged 44–65 stratified by MCI status (yes/no) and PTSD status (yes/no) and matched for age in years, sex (male vs. female), race (white, black, and other), and educational attainment (high school or less, some college / technical school, and university degree), and occupation on September 11, 2001 (law enforcement vs. other) underwent fMRI using a 3T Siemens Biograph MR scanner. A single 10-minute continuous functional MR sequence was acquired while participants were at rest with their eyes open. Group-level analyses were conducted using SPM-12, with correction for multiple comparisons using AFNI's 3dClustSim. Based on this threshold, the number of comparisons in our imaging volume, and the smoothness of our imaging data as measured by 3dFWHMx-acf, a minimum cluster size of 1134 voxels was required to have a corrected p . .05 with 2-sided thresholding. Spherical 3 mm seeds were placed in the dorsal (4, -50, 26) and ventral (4, -60, 46) posterior cingulate cortex (PCC).
Results:
Individuals with PTSD demonstrated significantly less connectivity of the dorsal posterior cingulate cortex (PCC) with medial insula (T = 5.21), subthalamic nucleus (T = 4.66), and postcentral gyrus (T = 3.81). There was no difference found in this study for connectivity between groups stratified by MCI status. There were no significant results for the ventral PCC seed.
Conclusions:
Contrary to hypotheses that were driven by a study of cortical thickness in WTC responders, the impact of PTSD appears to outweigh the impact of MCI on dorsal DMN connectivity among WTC responders stratified by PTSD and MCI status. This study is limited by several issues, including low number of female and minority participants, relatively small group cell sizes (n = 23–27 per cell), a brief resting state sequence (10 minutes), and lack of a non-WTC control group. Importantly, responders are a unique population so generalizability to other populations may be limited. Individuals in the current study are now being followed longitudinally to relate baseline resting state functional connectivity with cognitive changes and changes in connectivity over a four-year period.
Dietary guidelines are increasingly promoting mostly plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons. It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. We modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55 % female) from the Childhood Determinants of Adult Health study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using FFQ: 2004–2006, 2009–2011 and 2017–2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017–2019 (aged 39–49 years) using homoeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 10·5 percentage points, 95 % CI (4·1, 17·4)). Adjustment for waist circumference attenuated this association by 61·7 %. Replacing red meat with either legumes, nuts/seeds or wholegrains was likewise associated with higher insulin sensitivity. Point estimates were similar but less precise when replacing processed meat with plant-based alternatives. Our modelling suggests that regularly replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity. Further, abdominal adiposity may be an important mediator in this relationship. Our findings support advice to prioritise plant-based sources of protein at the expense of red meat consumption.
This article looks at four families living in and around the small town of Gatchina, not far from St Petersburg, Russia, in the long nineteenth century. Their family histories are recreated from archival files based in tsarist Russia's system of social estates (soslovie), supplemented by city directories, newspapers, and many other sources. Taken together, the four family histories expand our understanding of tsarist Russia's middle classes in two ways. First, they highlight the role that women played in families as economic actors and as agents of their own destiny. Second, they demonstrate the role that social mobility did and did not play in maintaining families across the long nineteenth century. In addition, they demonstrate some of the ways in which the Russian empire's experience of the nineteenth century differed from a standard Eurocentric narrative, in particular in the way that ‘archaic’ and ‘modern’ worlds existed simultaneously.
Valproate is a licensed medicine prescribed within mental health settings for bipolar disorder. It is a known teratogen, affecting approximately 20,000 people and costing the NHS £181 billion. This was a multidisciplinary project involving Surrey Heartlands Medicines Safety Team and Surrey and Borders Partnership NHS Foundation Trust, who developed a solution to reduce human suffering and cost by adhering to the Medicines and Healthcare Products Regulatory Agency (MHRA) valproate regulations through a clinical and digital redesign. The aim was to identify females in primary and secondary care across Surrey who take valproate for mental illness and to implement a pregnancy prevention programme for them by July 2022, using a digital clinical pathway supporting clinicians in the implementation process.
Methods
The method used was a combination of the Model for Improvement, the sequence for improvement from East London NHS Foundation Trust, UX design, and Agile project management. A valproate working group was formed with professionals from multiple disciplines to identify, understand and solve the problem. The solution was designed through co-production and project management methods that ensured a patient-centric solution.
Results
A digital registry of all females of childbearing potential who are prescribed valproate was created. A bespoke electronic GP referral form for valproate reviews was implemented. A one-stop valproate dashboard was developed to support documentation. A live digital visualisation feature was added within the secondary care electronic patient record to ensure compliance with MHRA guidelines. Easy-to-read materials for females with learning disabilities and sensitively worded appointment letters that inform patients of the risks and importance of attending annual reviews were created. In addition, collaboration with the National Valproate Patient Safety Officer allowed the implementation of Systematized Nomenclature of Medicine Clinical Terms (SNOMED) codes to simplify the exchange of clinical information between systems.
Conclusion
The project has the potential to reduce harm and improve the patient experience, serving as a template for other medications with strong regulatory controls. Collaboration between primary and secondary care, clinicians, pharmacists and digital colleagues, and co-design with people prescribed valproate were essential to the success of the project. Ongoing work is required to ensure valproate-related materials are available in an accessible format for every person prescribed valproate. Valproate has also been implicated in paternal adverse effects, and this project solution is future-proofed to identify men on valproate. Through this work, people will only be treated with valproate in a way that safeguards the health of unborn children.
When compared with the general population, people living with severe mental illness (SMI) are 1·8 times more likely to have obesity while in adult mental health secure units, rates of obesity are 20 % higher than the general population. In England, there are currently 490 000 people living with SMI. The aim of this systematic review was to collate and synthesise the available quantitative and qualitative evidence on a broad range of weight management interventions for adults living with SMI and overweight or obesity. Primary outcomes were reductions in BMI and body weight. Following sifting, eighteen papers were included in the final review, which detailed the results of nineteen different interventions; however, there was a lack of qualitative evidence. Pooled results for three studies (MD − 3·49, 95 % CI − 6·85, −0·13, P = 0·04) indicated a small effect in terms of body weight reduction but no effect on BMI for four studies (MD − 0·42, 95 % CI − 1·27, 0·44, P = 0·34). Key recommendations for future research included integration of qualitative methodology into experimental study design, a review of outcome measures and for study authors to follow standardised guidelines for reporting to facilitate complete and transparent reporting.
Despite its potential scalability, little is known about the outcomes of internet-based cognitive behaviour therapy (iCBT) for post-traumatic stress disorder (PTSD) when it is provided with minimal guidance from a clinician.
Aim:
To evaluate the outcomes of minimally guided iCBT for PTSD in a randomised control trial (RCT, Study 1) and in an open trial in routine community care (Study 2).
Method:
A RCT compared the iCBT course (n=21) to a waitlist control (WLC, n=19) among participants diagnosed with PTSD. The iCBT group was followed up 3 months post-treatment. In Study 2, treatment outcomes were evaluated among 117 adults in routine community care. PTSD symptom severity was the primary outcome in both studies, with psychological distress and co-morbid anxiety and depressive symptoms providing secondary outcomes.
Results:
iCBT participants in both studies experienced significant reductions in PTSD symptom severity from pre- to post-treatment treatment (within-group Hedges’ g=.72–1.02), with RCT findings showing maintenance of gains at 3-month follow-up. The WLC group in the RCT also significantly improved, but Study 1 was under-powered and the medium between-group effect favouring iCBT did not reach significance (g=0.64; 95% CI, –0.10–1.38).
Conclusions:
This research provides preliminary support for the utility of iCBT for PTSD when provided with minimal clinician guidance. Future studies are needed to clarify the effect of differing levels of clinician support on PTSD iCBT outcomes, as well as exploring how best to integrate iCBT into large-scale, routine clinical care of PTSD.
Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.
Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.
We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.
Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).
Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.
Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid (IFA) supplements containing 60 mg of Fe. We aimed to assess the effect of MMS v. IFA on neonatal mortality stratified by Fe dose in each supplement.
Methods:
We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS v. IFA on neonatal mortality in subgroups of trials (n 13) providing the same or different amounts of Fe, that is, MMS with 60 mg of Fe v. IFA with 60 mg of Fe; MMS with 30 mg of Fe v. IFA with 30 mg of Fe; MMS with 30 mg of Fe v. IFA with 60 mg of Fe; and MMS with 20 mg of Fe v. IFA with 60 mg of Fe.
Results:
There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg v. IFA with 60 mg of Fe (7 trials, 14 114 participants), yielded a non-significant risk ratio of 1·12 (95 % CI 0·83 to 1·50).
Conclusion:
Neonatal mortality did not differ between MMS and IFA regardless of Fe dose in either supplement.
We assessed the prevalence of antibiotic prescriptions among ambulatory patients tested for coronavirus disease 2019 (COVID-19) in a large public US healthcare system and found a low overall rate of antibiotic prescriptions (6.7%). Only 3.8% of positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests were associated with an antibiotic prescription within 7 days.
The COVID-19 pandemic has highlighted the impact work can have on healthcare workers and the importance of staff support services. Rapid guidance was published to encourage preventive and responsive support for healthcare workers.
Aims
To understand mental healthcare staff's help-seeking behaviours and access to support at work in response to the COVID-19 pandemic, to inform iterative improvements to provision of staff support.
Method
We conducted a formative appraisal of access to support and support needs of staff in a National Health Service mental health trust. This involved 11 semi-structured individual interviews using a topic guide. Five virtual staff forums were additional sources of data. Reflexive thematic analysis was used to identify key themes.
Results
Peer-based, within-team support was highly valued and sought after. However, access to support was negatively affected by work pressures, physical distancing and perceived cultural barriers.
Conclusions
Healthcare organisations need to help colleagues to support each other by facilitating open, diverse workplace cultures and providing easily accessible, safe and reflective spaces. Future research should evaluate support in the evolving work contexts imposed by COVID-19 to inform interventions that account for differences across healthcare workforces.