Ecological marginalization is widespread and increases extinction risk in mammals.

Human land-use results in widespread range change across taxa. Anthropogenic pressures can result in species' realized niches expanding, shifting, or contracting. Marginalization occurs when contraction constrains species to the geographic or ecological extremes of their historic niche. Using 4,785 terrestrial mammal species, we show that range contraction results in niche space and habitat diversity loss. Additionally, ecological marginalization is a common consequence of range contraction caused by human land use change. Remnant populations become located in the climatic and topographic extremes of their historic niche that are more likely to be at the periphery of their historic niche at greater distances from historic niche centroids. This ecological marginalization is associated with poor performance and increased extinction risk independent of geographic range loss. Range loss and marginalization may create a "double whammy" in vulnerable groups, such as large-bodied species and species with small geographical range size. Our results reveal a hitherto unrecognized conservation threat that is vital to incorporate into conservation assessment and management.

Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids in Euphorbia peplus.

Most macro- and polycyclic Euphorbiaceae diterpenoids derive from the common C20 precursor casbene. While the biosynthetic pathway from casbene to the lathyrane jolkinol C is characterized, pathways to other more complex classes of bioactive diterpenoids remain to be elucidated. A metabolomics-guided transcriptomic approach and a genomics approach that led to the discovery of two casbene-derived diterpenoid gene clusters yielded a total of 68 candidate genes that were transiently expressed in Nicotiana benthamiana for activity toward jolkinol C and other lathyranes. We report two short-chain dehydrogenases/reductases (SDRs), identified by RNA sequencing to be highly expressed in Euphorbia peplus latex. One of these, EpSDR-5, is a C3-ketoreductase, converting jolkinol C to the lathyrane jolkinol E. Gene function of EpSDR-5 was further confirmed by heterologous expression in Saccharomyces cerevisiae. To investigate the in vivo role of EpSDR-5, we established virus-induced gene silencing (VIGS) in E. peplus, resulting in a significant reduction in jatrophanes and a corresponding increase in ingenanes. VIGS of Casbene Synthase results in a major reduction in both jatrophanes and ingenanes, the two most abundant classes of E. peplus diterpenoids. VIGS of CYP71D365 had a similar effect, consistent with the previously determined role of this gene in the pathway to jolkinol C. These results point to jolkinol C being a branch point intermediate in the pathways to ingenanes and jatrophanes with EpSDR-5 responsible for the first step from jolkinol C to jatrophane production.

Interventions on gender equity in the workplace: a scoping review.

BACKGROUND: Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). METHODS: Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. RESULTS: We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. CONCLUSIONS: There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. TRIAL REGISTRATION: Open Science Framework https://osf.io/x8yae .

Evaluation of the diagnostic accuracy of exome sequencing and its impact on diagnostic thinking for patients with rare disease in a publicly funded health care system: A prospective cohort study.

PURPOSE: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases. METHODS: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests. RESULTS: Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses. CONCLUSION: We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test.

Morphology, repulsion, and ordering of red blood cells in viscoelastic flows under confinement.

Red blood cells (RBC), the primary carriers of oxygen in the body, play a crucial role across several biomedical applications, while also being an essential model system of a deformable object in the microfluidics and soft matter fields. However, RBC behavior in viscoelastic liquids, which holds promise in enhancing microfluidic diagnostic applications, remains poorly studied. We here show that using viscoelastic polymer solutions as a suspending carrier causes changes in the clustering and shape of flowing RBC in microfluidic flows when compared to a standard Newtonian suspending liquid. Additionally, when the local RBC concentration increases to a point where hydrodynamic interactions take place, we observe the formation of equally-spaced RBC structures, resembling the viscoelasticity-driven ordered particles observed previously in the literature, thus providing the first experimental evidence of viscoelasticity-driven cell ordering. The observed RBC ordering, unaffected by polymer molecular architecture, persists as long as the surrounding medium exhibits shear-thinning, viscoelastic properties. Complementary numerical simulations reveal that viscoelasticity-induced repulsion between RBCs leads to equidistant structures, with shear-thinning modulating this effect. Our results open the way for the development of new biomedical technologies based on the use of viscoelastic liquids while also clarifying fundamental aspects related to multibody hydrodynamic interactions in viscoelastic microfluidic flows.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Describing the content of trial recruitment interventions using the TIDieR reporting checklist: a systematic methodology review.

BACKGROUND: Recruiting participants to clinical trials is an ongoing challenge, and relatively little is known about what recruitment strategies lead to better recruitment. Recruitment interventions can be considered complex interventions, often involving multiple components, targeting a variety of groups, and tailoring to different groups. We used the Template for Intervention Description and Replication (TIDieR) reporting checklist (which comprises 12 items recommended for reporting complex interventions) to guide the assessment of how recruitment interventions are described. We aimed to (1) examine to what extent we could identify information about each TIDieR item within recruitment intervention studies, and (2) observe additional detail for each item to describe useful variation among these studies. METHODS: We identified randomized, nested recruitment intervention studies providing recruitment or willingness to participate rates from two sources: a Cochrane review of trials evaluating strategies to improve recruitment to randomized trials, and the Online Resource for Research in Clinical triAls database. First, we assessed to what extent authors reported information about each TIDieR item. Second, we developed descriptive categorical variables for 7 TIDieR items and extracting relevant quotes for the other 5 items. RESULTS: We assessed 122 recruitment intervention studies. We were able to extract information relevant to most TIDieR items (e.g., brief rationale, materials, procedure) with the exception of a few items that were only rarely reported (e.g., tailoring, modifications, planned/actual fidelity). The descriptive variables provided a useful overview of study characteristics, with most studies using various forms of informational interventions (55%) delivered at a single time point (90%), often by a member of the research team (59%) in a clinical care setting (41%). CONCLUSIONS: Our TIDieR-based variables provide a useful description of the core elements of complex trial recruitment interventions. Recruitment intervention studies report core elements of complex interventions variably; some process elements (e.g., mode of delivery, location) are almost always described, while others (e.g., duration, fidelity) are reported infrequently, with little indication of a reason for their absence. Future research should explore whether these TIDieR-based variables can form the basis of an approach to better reporting of elements of successful recruitment interventions.

The Biggest Unmet Needs in Cardiovascular Disease Prevention in 2023.

BACKGROUND: While the major causes of atherosclerotic cardiovascular disease (CVD) are known, clinical audits continue to show inadequate risk factor control, even in the highest risk subjects. More effective risk estimation methods may help, and advances in this field are outlined. There exist excellent guidelines on CVD prevention, but their very length and complexity may limit their use. Other factors inhibiting guideline implementation are explored. SUMMARY: While new medications continue to be developed, the real challenges to effective CVD prevention are societal and political. Both nationally and at European levels, cohesive, integrated strategies with defined responsibilities and accountability are needed, together with empowerment of people to understand the concept of risk and what they can do about it. KEY MESSAGES: There are profound health inequalities between and within countries that need to be addressed.

Decision aids for people facing health treatment or screening decisions.

BACKGROUND: Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017. OBJECTIVES: To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach. SEARCH METHODS: We conducted the updated search for the period of 2015 (last search date) to March 2022 in CENTRAL, MEDLINE, Embase, PsycINFO, EBSCO, and grey literature. The cumulative search covers database origins to March 2022. SELECTION CRITERIA: We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened citations for inclusion, extracted intervention and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made (informed values-based choice congruence) and the decision-making process, such as knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision-making, and adverse events. Secondary outcomes were choice, confidence in decision-making, adherence to the chosen option, preference-linked health outcomes, and impact on the healthcare system (e.g. consultation length). We pooled results using mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs), applying a random-effects model. We conducted a subgroup analysis of 105 studies that were included in the previous review version compared to those published since that update (n = 104 studies). We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of the evidence. MAIN RESULTS: This update added 104 new studies for a total of 209 studies involving 107,698 participants. The patient decision aids focused on 71 different decisions. The most common decisions were about cardiovascular treatments (n = 22 studies), cancer screening (n = 17 studies colorectal, 15 prostate, 12 breast), cancer treatments (e.g. 15 breast, 11 prostate), mental health treatments (n = 10 studies), and joint replacement surgery (n = 9 studies). When assessing risk of bias in the included studies, we rated two items as mostly unclear (selective reporting: 100 studies; blinding of participants/personnel: 161 studies), due to inadequate reporting. Of the 209 included studies, 34 had at least one item rated as high risk of bias. There was moderate-certainty evidence that patient decision aids probably increase the congruence between informed values and care choices compared to usual care (RR 1.75, 95% CI 1.44 to 2.13; 21 studies, 9377 participants). Regarding attributes related to the decision-making process and compared to usual care, there was high-certainty evidence that patient decision aids result in improved participants' knowledge (MD 11.90/100, 95% CI 10.60 to 13.19; 107 studies, 25,492 participants), accuracy of risk perceptions (RR 1.94, 95% CI 1.61 to 2.34; 25 studies, 7796 participants), and decreased decisional conflict related to feeling uninformed (MD -10.02, 95% CI -12.31 to -7.74; 58 studies, 12,104 participants), indecision about personal values (MD -7.86, 95% CI -9.69 to -6.02; 55 studies, 11,880 participants), and proportion of people who were passive in decision-making (clinician-controlled) (RR 0.72, 95% CI 0.59 to 0.88; 21 studies, 4348 participants). For adverse outcomes, there was high-certainty evidence that there was no difference in decision regret between the patient decision aid and usual care groups (MD -1.23, 95% CI -3.05 to 0.59; 22 studies, 3707 participants). Of note, there was no difference in the length of consultation when patient decision aids were used in preparation for the consultation (MD -2.97 minutes, 95% CI -7.84 to 1.90; 5 studies, 420 participants). When patient decision aids were used during the consultation with the clinician, the length of consultation was 1.5 minutes longer (MD 1.50 minutes, 95% CI 0.79 to 2.20; 8 studies, 2702 participants). We found the same direction of effect when we compared results for patient decision aid studies reported in the previous update compared to studies conducted since 2015. AUTHORS' CONCLUSIONS: Compared to usual care, across a wide variety of decisions, patient decision aids probably helped more adults reach informed values-congruent choices. They led to large increases in knowledge, accurate risk perceptions, and an active role in decision-making. Our updated review also found that patient decision aids increased patients' feeling informed and clear about their personal values. There was no difference in decision regret between people using decision aids versus those receiving usual care. Further studies are needed to assess the impact of patient decision aids on adherence and downstream effects on cost and resource use.

Interventions that have potential to help older adults living with social frailty: a systematic scoping review.

BACKGROUND: The impact of social frailty on older adults is profound including mortality risk, functional decline, falls, and disability. However, effective strategies that respond to the needs of socially frail older adults are lacking and few studies have unpacked how social determinants operate or how interventions can be adapted during periods requiring social distancing and isolation such as the COVID-19 pandemic. To address these gaps, we conducted a scoping review using JBI methodology to identify interventions that have the best potential to help socially frail older adults (age ≥65 years). METHODS: We searched MEDLINE, CINAHL (EPSCO), EMBASE and COVID-19 databases and the grey literature. Eligibility criteria were developed using the PICOS framework. Our results were summarized descriptively according to study, patient, intervention and outcome characteristics. Data synthesis involved charting and categorizing identified interventions using a social frailty framework.  RESULTS: Of 263 included studies, we identified 495 interventions involving ~124,498 older adults who were mostly female. The largest proportion of older adults (40.5%) had a mean age range of 70-79 years. The 495 interventions were spread across four social frailty domains: social resource (40%), self-management (32%), social behavioural activity (28%), and general resource (0.4%). Of these, 189 interventions were effective for improving loneliness, social and health and wellbeing outcomes across psychological self-management, self-management education, leisure activity, physical activity, Information Communication Technology and socially assistive robot interventions. Sixty-three interventions were identified as feasible to be adapted during infectious disease outbreaks (e.g., COVID-19, flu) to help socially frail older adults. CONCLUSIONS: Our scoping review identified promising interventions with the best potential to help older adults living with social frailty.

Superoxide is promoted by sucrose and affects amplitude of circadian rhythms in the evening.

Plants must coordinate photosynthetic metabolism with the daily environment and adapt rhythmic physiology and development to match carbon availability. Circadian clocks drive biological rhythms which adjust to environmental cues. Products of photosynthetic metabolism, including sugars and reactive oxygen species (ROS), are closely associated with the plant circadian clock, and sugars have been shown to provide metabolic feedback to the circadian oscillator. Here, we report a comprehensive sugar-regulated transcriptome of Arabidopsis and identify genes associated with redox and ROS processes as a prominent feature of the transcriptional response. We show that sucrose increases levels of superoxide (O2-), which is required for transcriptional and growth responses to sugar. We identify circadian rhythms of O2--regulated transcripts which are phased around dusk and find that O2- is required for sucrose to promote expression of TIMING OF CAB1 (TOC1) in the evening. Our data reveal a role for O2- as a metabolic signal affecting transcriptional control of the circadian oscillator in Arabidopsis.

Nurse managers' perceptions of the prospective acceptability of an implementation leadership training programme: A qualitative descriptive study.

AIM: To explore the prospective acceptability of an implementation leadership training programme prototype for nurse managers in China to implement evidence-based practices, from the perspectives of potential programme participants and deliverers. DESIGN: A qualitative descriptive study was conducted in Spring 2022 at three tertiary hospitals in Hunan, China. METHODS: We conducted individual semi-structured interviews with unit-level nurse managers (n = 14), including 12 potential participants, and two potential deliverers that have been involved in developing the programme prototype. Interview questions and thematic analysis were guided by the Theoretical Framework of Acceptability. RESULTS: After reviewing the programme content, potential participants and deliverers reported that unit nurse managers would benefit from engaging in the programme, acknowledging that the programme fit with professional nursing values for implementing research evidence. They expressed positive views about being involved in producing academic papers through the training process, and interactive multi-modal training activities such as group work, experience-sharing and coaching. Seven participants were not very confident about being fully engaged in the training, as they could not navigate the English research literature. Both participants and deliverers highlighted factors that would influence their participation, including time constraints, the impact of the COVID-19 pandemic, and support from senior organizational leadership. CONCLUSIONS: The training programme prototype was perceived to be useful and acceptable. The multimodal training activities were considered a strength and managers expressed an interest in writing academic papers about their implementation processes. Support from senior hospital leaders and programme deliverers was identified as critical to the training programme's success. IMPACT: The study helps understand nurse managers' perceptions and concerns of participating in an implementation leadership training programme and could inform the development and refinement of similar programmes in various nursing contexts globally.

Youth, caregiver and healthcare professional perspectives on planning the implementation of a trauma-informed care programme: A qualitative study.

AIMS: To explore youth, caregiver and staff perspectives on their vision of trauma-informed care, and to identify and understand potential considerations for the implementation of a trauma-informed care programme in an inpatient mental health unit within a paediatric hospital. DESIGN AND METHODS: We applied the Interpretive Description approach, guided by complexity theory and the Implementation Roadmap, and used Applied Thematic Analysis methods. FINDINGS: Twenty-five individuals participated in individual or group interviews between March and June 2022, including 21 healthcare professionals, 3 youth and 1 caregiver. We identified two overarching themes. The first theme, 'Understanding and addressing the underlying reasons for distress', related to participants' understanding and vision of TIC in the current setting comprising: (a) 'Participants' understanding of TIC'; (b) 'Trauma screening and trauma processing within TIC'; (c) 'Taking "a more individualized approach"'; (d) 'Unit programming'; and (e) "Connecting to the community". The second theme, 'Factors that support or limit successful TIC implementation' comprises: (a) 'The need for a broad "cultural shift"'; (b) 'The physical environment on the unit'; and (c) 'Factors that may limit successful implementation'. CONCLUSION: We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of engagement with youth, caregivers and staff in trauma-informed care delivery and implementation, (b) trauma-informed care core programme components, (c) factors that may support or limit success in implementing trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration (partnering with external organizations and sectors). IMPACT: When implementing TIC, there is an ongoing need to increase clarity regarding TIC interventions and implementation initiatives. Youth, caregiver and healthcare professional participants shared considerations important for planning the delivery and implementation of trauma-informed care in their setting. We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of relational engagement, (b) trauma-informed care programme components, (c) factors that may support or limit successful implementation of trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration. Organizations wishing to implement trauma-informed care should consider ongoing engagement with all relevant knowledge user groups throughout the process. REPORTING METHOD: Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: The local hospital research institute's Patient and Family Advisory Committee reviewed the draft study methods and provided feedback.

Development of a training program prototype to enhance implementation leadership competencies and behaviours of Chinese unit nurse managers: a qualitative descriptive study.

BACKGROUND: Unit nurse managers hold essential positions that can facilitate implementation of evidence-based practice. Studies showed that nurse managers in China lacked competencies and behaviours necessary to lead evidence-based practice implementation. The aim of the current study was to develop a context-fit training program prototype to enhance leadership competencies and behaviours regarding evidence-based practice implementation of Chinese unit nurse managers. METHOD: We used a descriptive qualitative study design and followed the integrated knowledge translation approach to co-develop the prototype in a tertiary hospital in Changsha, China. Seven nurse managers from the participated hospital and a researcher co-developed the prototype based on the Ottawa Model of Implementation Leadership (O-MILe). The development process encompassed four phases from November 2021 to March 2022 that involved group discussions (n = 4) and individual interviews (n = 21). All data were analysed by two independent researchers using the thematic analysis method. RESULTS: Managers agreed that all O-MILe behaviours were important to evidence-based practice implementation, and only minor modifications were needed for clarification and adaptation. The actions managers identified that could operationalize the leadership behaviours were related to current clinical practices, evidence-based practice, nurses, patients, interprofessional staff members, incentives and resources, organization and external entities. Three types of general competencies related to evidence-based practice, professional nursing, and implementation leadership were identified. Multimodal activities such as lectures, experience sharing, group discussions, plan development and coaching were suggested to deliver the training program. CONCLUSIONS: All O-MILe leadership behaviours were perceived as essential for unit nurse managers to lead EBP implementation in the hospital context in China. We identified the leadership actions and the competencies required for nursing managers to implement EBP in China. Further studies are required to evaluate the acceptability and impact of this prototype. Further studies with large sample sizes across various clinical settings are needed to facilitate the generalization of the findings and gain an in-depth understanding of the program.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Exome and genome sequencing for rare genetic disease diagnosis: A scoping review and critical appraisal of clinical guidance documents produced by genetics professional organizations.

PURPOSE: Exome and genome sequencing have rapidly transitioned from research methods to widely used clinical tests for diagnosing rare genetic diseases. We sought to synthesize the topics covered and appraise the development processes of clinical guidance documents generated by genetics professional organizations. METHODS: We conducted a scoping review of guidance documents published since 2010, systematically identified in peer-reviewed and gray literature, using established methods and reporting guidelines. We coded verbatim recommendations by topic using content analysis and critically appraised documents using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. RESULTS: We identified 30 guidance documents produced by 8 organizations (2012-2022), yielding 611 recommendations covering 21 topics. The most common topic related to findings beyond the primary testing indication. Mean AGREE II scores were low across all 6 quality domains; scores for items related to rigor of development were among the lowest. More recently published documents generally received higher scores. CONCLUSION: Guidance documents included a broad range of recommendations but were of low quality, particularly in their rigor of development. Developers should consider using tools such as AGREE II and basing recommendations on living knowledge syntheses to improve guidance development in this evolving space.

Bridging clinical care and research in Ontario, Canada: Maximizing diagnoses from reanalysis of clinical exome sequencing data.

We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians. Reanalysis of clinically relevant genes identified diagnoses in 4% (13/287); four were missed by clinical testing. Translational research methods, including analysis of novel candidate genes, identified candidates in 21% (61/287). Of these, 24 families have additional evidence through data sharing to support likely diagnoses (8% of cohort). This study indicates few diagnoses are missed by clinical laboratories, the incremental gain from reanalysis of clinically-relevant genes is modest, and the highest yield comes from validation of novel disease-gene associations. Future implementation of translational research methods, including continued reporting of compelling genes of uncertain significance by clinical laboratories, should be considered to maximize diagnoses.

Exploring the relationship between softness and excess entropy in glass-forming systems.

We explore the relationship between a machine-learned structural quantity (softness) and excess entropy in simulations of supercooled liquids. Excess entropy is known to scale well the dynamical properties of liquids, but this quasi-universal scaling is known to breakdown in supercooled and glassy regimes. Using numerical simulations, we test whether a local form of the excess entropy can lead to predictions similar to those made by softness, such as the strong correlation with particles' tendency to rearrange. In addition, we explore leveraging softness to compute excess entropy in the traditional fashion over softness groupings. Our results show that the excess entropy computed over softness-binned groupings is correlated with activation barriers to rearrangement.

Planning and implementing practice changes in Ontario maternal-newborn hospital units: a secondary qualitative analysis.

BACKGROUND: Moving evidence into practice is complex, and pregnant and birthing people and their infants do not always receive care that aligns with the best available evidence. Implementation science can inform how to effectively move evidence into practice. While there are a growing number of examples of implementation science being studied in maternal-newborn care settings, it remains unknown how real-world teams of healthcare providers and leaders approach the overall implementation process when making practice changes. The purpose of this study was to describe maternal-newborn hospital teams' approaches to implementing practice changes. We aimed to identify what implementation steps teams take (or not) and identify strengths and potential areas for improvement based on best practices in implementation science. METHODS: We conducted a supplementary qualitative secondary analysis of 22 interviews completed in 2014-2015 with maternal-newborn nursing leaders in Ontario, Canada. We used directed content analysis to code the data to seven steps in an implementation framework (Implementation Roadmap): identify the problem and potential best practice; assemble local evidence; select and customize best practice; discover barriers and drivers; tailor implementation strategies; field-test, plan evaluation, prepare to launch; launch, evaluate, and sustain. Frequency counts are presented for each step. RESULTS: Participants reported completing a median of 4.5 of 7 Implementation Roadmap steps (range = 3-7), with the most common being identifying a practice problem. Other steps were described less frequently (e.g., selecting and adapting evidence, field-testing, outcome evaluation) or discussed frequently but not optimally (e.g., barriers assessment). Participants provided examples of how they engaged point-of-care staff throughout the implementation process, but provided fewer examples of engaging pregnant and birthing people and their families. Some participants stated they used a formal framework or process to guide their implementation process, with the most common being quality improvement approaches and tools. CONCLUSIONS: We identified variability across the 22 hospitals in the implementation steps taken. While we observed many strengths, we also identified areas where further support may be needed. Future work is needed to create opportunities and resources to support maternal-newborn healthcare providers and leaders to apply principles and tools from implementation science to their practice change initiatives.

Turning the tide on inequity through systematic equity action-analysis.

BACKGROUND: Collective agreement about the importance of centering equity in health research, practice, and policy is growing. Yet, responsibility for advancing equity is often situated as belonging to a vague group of 'others', or delegated to the leadership of 'equity-seeking' or 'equity-deserving' groups who are tasked to lead systems transformation while simultaneously navigating the violence and harms of oppression within those same systems. Equity efforts also often overlook the breadth of equity scholarship. Harnessing the potential of current interests in advancing equity requires systematic, evidence-guided, theoretically rigorous ways for people to embrace their own agency and influence over the systems in which they are situated. ln this article, we introduce and describe the Systematic Equity Action-Analysis (SEA) Framework as a tool that translates equity scholarship and evidence into a structured process that leaders, teams, and communities can use to advance equity in their own settings. METHODS: This framework was derived through a dialogic, critically reflective and scholarly process of integrating methodological insights garnered over years of equity-centred research and practice. Each author, in a variety of ways, brought engaged equity perspectives to the dialogue, bringing practical and lived experience to conversation and writing. Our scholarly dialogue was grounded in critical and relational lenses, and involved synthesis of theory and practice from a broad range of applications and cases. RESULTS: The SEA Framework balances practices of agency, humility, critically reflective dialogue, and systems thinking. The framework guides users through four elements of analysis (worldview, coherence, potential, and accountability) to systematically interrogate how and where equity is integrated in a setting or object of action-analysis. Because equity issues are present in virtually all aspects of society, the kinds of 'things' the framework could be applied to is only limited by the imagination of its users. It can inform retrospective or prospective work, by groups external to a policy or practice setting (e.g., using public documents to assess a research funding policy landscape); or internal to a system, policy, or practice setting (e.g., faculty engaging in a critically reflective examination of equity in the undergraduate program they deliver). CONCLUSIONS: While not a panacea, this unique contribution to the science of health equity equips people to explicitly recognize and interrupt their own entanglements in the intersecting systems of oppression and injustice that produce and uphold inequities.