Genetic factors predict hybrid formation in the British flora.

Natural hybridization can have a profound evolutionary impact, with consequences ranging from the extinction of rare taxa to the origin of new species. Natural hybridization is particularly common in plants; however, our understanding of the general factors that promote or prevent hybridization is hampered by the highly variable outcomes in different lineages. Here, we quantify the influence of different predictors on hybrid formation across species from an entire flora. We combine estimates of hybridization with ecological attributes and a new species-level phylogeny for over 1,100 UK flowering plant species. Our results show that genetic factors, particularly parental genetic distance, as well as phylogenetic position and ploidy, are key determinants of hybrid formation, whereas many other factors such as range overlap and genus size explain much less variation in hybrid formation. Overall, intrinsic genetic factors shape the evolutionary and ecological consequences of natural hybridization across species in a flora.

Pupal Exuviae of Culex Pipiens L. (Diptera: Culicidae) Can be Utilised as a Non-Invasive Method of Biotype Differentiation.

BACKGROUND: Culex pipiens L. is a principal vector of zoonotic arboviruses in Europe, acting in both an amplification role in enzootic transmission between avian hosts and as a bridge vector between avian hosts and mammals. The species consists of two forms which are indistinguishable using morphological methods but possess varying ecological and physiological traits that influence their vector capacity. In this study we validate methods that can be used to extract trace DNA from single pupal exuviae of Cx. pipiens for use in molecular speciation of samples. These DNA extraction methods are compared using measurement of the total yield and successful identification using a real-time polymerase chain reaction (PCR) assay. RESULTS: Genomic DNA was initially extracted from colony-derived individuals using an ethanol precipitation method, two commercially available DNA extraction kits: DNeasy® Blood & Tissue Kit (Qiagen, UK) and Wizard® SV Genomic DNA Purification System (Promega, UK) and a direct real-time PCR method. Time elapsed between eclosion and processing of pupae significantly influenced Cx. pipiens form identification as nucleic acid concentration and PCR amplification success decreased with increased time elapsed. Real-time PCR amplification success, however, was not shown to vary significantly between the three extraction methods, with all methods successfully identifying all samples, but the direct real-time PCR method achieved a lesser amplification success rate of 70% (n = 20 for each treatment). More variable results were produced when field-derived exuviae were used, with no significant difference in real-time PCR amplification success found across the four methods and a lower overall rate of successful identification of 55-80%. CONCLUSIONS: This study shows that both colony and field derived Cx. pipiens pupal exuviae can be a useful non-invasive source of trace DNA permitting accurate biotype differentiation for at least twenty-four hours post-eclosion. The significance and utility of this technique in ecological and behavioural studies of Cx. pipiens is discussed and recommendations made for use according to experimental scenario.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

"What Is the Most Important to Them?" Swiss Health Care Proxies, Nurses, and Physicians Discuss Planning Practices for Aged Care Residents Who No Longer Have Medical Decision-Making Capacity.

INTRODUCTION: Multiple morbidities, including neurodegenerative diseases such as dementia, which result in diminished decision-making capacity (DMC), make care and care planning complicated for residential aged care facility (RACF) residents. While advance care planning has been highlighted as essential for ensuring that this population receives care that is coherent with their wishes, there are few models specifically designed for this population. This study aimed to explore the current practices for care planning and decision-making for Swiss RACF residents who no longer have medical DMC. METHODS: Semi-structured focus groups were conducted with 23 nurses in three RACFs and with 13 physicians working in 9 RACFs. Semi-structured interviews were conducted with 18 health care proxies of 16 residents without DMC. Thematic analysis was conducted to identify the most salient themes across the dataset. RESULTS: Analyses identified many collaborative processes between nurses, physicians, and health care proxies including family meetings, reconstructing residents' presumed will, making anticipatory decisions, and documenting these decisions. These processes were, however, highly variable and differed between institutions and between residents within each facility, with a lack of standardization. This variability was highlighted to be problematic for information transmission within facilities and in case of hospital or facility transfer. CONCLUSIONS: These results highlight the importance of standardized yet flexible processes of care planning for people who no longer have DMC and provide insights for the development of such models specifically designed to address this problem.

Prevalence and risk of sexual violence victimization among mental health service users: a systematic review and meta-analyses.

PURPOSE: People with mental disorders are more likely to experience sexual violence than the general population, but little is known about the prevalence of sexual violence in people who use psychiatric services. This paper aims to estimate the prevalence and odds of sexual violence victimisation within mental health services by gender and mental health setting (i.e. inpatient, outpatient and mixed settings). METHODS: This study is a systematic review and meta-analysis (PROSPERO registration number: CRD4201810019). Three databases (Medline, Embase, PsychINFO) were searched and citation tracking, and reference screening of included studies was conducted. Studies were included if the prevalence and/or risk of sexual violence in psychiatric service users were reported or calculable across the past year or adult lifetime. The methodological quality of included studies was assessed. A random effects meta-analyses was conducted to estimate odds ratios and pooled prevalence estimates of sexual violence in different mental health settings. RESULTS: Twenty-six studies were included encompassing 197,194 participants. The meta-analyses revealed high pooled prevalence estimates and increased odds of sexual violence victimisation in male and female psychiatric service users compared to non-psychiatric service users. CONCLUSIONS: Mental health practitioners should be trained to respond effectively to disclosures of sexual violence, particularly from these vulnerable groups. Future sexual violence interventions should consider mental health as a treatment outcome.

Ventilator-tube holder for mobilising patients with a tracheostomy: A pilot usability study (TrachVest).

INTRODUCTION: Patients in intensive care may have a tracheostomy and be dependent on a respiratory ventilator while yet conscious and able to mobilise. Early rehabilitation is known to be key to patient recovery. However, for these patients, therapy staff members are required to manage the ventilator tubing in addition to other patient-connected equipment whilst focussing on patient mobility and progress. A technical garment (TrachVest) was designed to hold the ventilator tubing securely during these therapeutic mobilisations. METHODS: We conducted a mixed-methods study to evaluate the use of this garment in an intensive care unit setting. The aim was to determine potential effects on patient safety, its potential benefits, and usability. Research methods included direct observations, user questionnaires (quantitative and qualitative), and staff focus groups. RESULTS: A total of 14 therapy sessions with the garment were observed, involving nine patients and 10 staff. Eleven staff members participated in two focus groups, including two previously involved in the therapy sessions. Therapy sessions consisted of a range of activities including sitting on the edge of the bed, transferring from bed to chair (including use of hoists), and mobilising with walking aids. Overall, staff members felt that the garment was easy to use and would likely improve patient safety during mobilisations. The main benefits were staff reassurance, allowing them to focus on therapy, and in potentially reducing the number of staff members needed for particular activities. Patient characteristics were found to be influential on the perceived utility, and TrachVest may have greater benefit for patients who have greater physical function (e.g., able to actively participate in rehabilitation) and can mobilise at least from bed to chair. Experience of using the TrachVest and of patient capabilities was thought to be key to knowing when it would be most useful. CONCLUSION: Within this pilot usability study, participants, both staff and patients, reported that the TrachVest garment designed to support ventilator tubing during rehabilitation to be highly useable and beneficial to supporting rehabilitation in this patient group.

Temporal change in floral availability leads to periods of resource limitation and affects diet specificity in a generalist pollinator.

Generalist species are core components of ecological networks and crucial for the maintenance of biodiversity. Generalist species and networks are expected to be more resilient, and therefore understanding the dynamics of specialization and generalization in ecological networks is a key focus in a time of rapid global change. Whilst diet generalization is frequently studied, our understanding of how it changes over time is limited. Here we explore temporal variation in diet specificity in the honeybee (Apis mellifera), using pollen DNA metabarcoding of honey samples, through the foraging season, over two years. We find that, overall, honeybees are generalists that visit a wide range of plants, but there is temporal variation in the degree of specialization. Temporal specialization of honeybee colonies corresponds to periods of resource limitation, identified as a lack of honey stores. Honeybees experience a lack of preferred resources in June when switching from flowering trees in spring to shrubs and herbs in summer. Investigating temporal patterns in specialization can identify periods of resource limitation that may lead to species and network vulnerability. Diet specificity must therefore be explored at different temporal scales in order to fully understand species and network stability in the face of ecological change.

Preferences for deinfibulation (opening) surgery and female genital mutilation service provision: A qualitative study.

OBJECTIVE: To explore the views of female genital mutilation (FGM) survivors, men and healthcare professionals (HCPs) on the timing of deinfibulation surgery and NHS service provision. DESIGN: Qualitative study informed by the sound of silence framework. SETTING: Survivors and men were recruited from three FGM prevalent areas of England. HCPs and stakeholders were from across the UK. SAMPLE: Forty-four survivors, 13 men and 44 HCPs. Ten participants at two community workshops and 30 stakeholders at a national workshop. METHODS: Hybrid framework analysis of 101 interviews and three workshops. RESULTS: There was no consensus across groups on the optimal timing of deinfibulation for survivors who wished to be deinfibulated. Within group, survivors expressed a preference for deinfibulation pre-pregnancy and HCPs antenatal deinfibulation. There was no consensus for men. Participants reported that deinfibulation should take place in a hospital setting and be undertaken by a suitable HCP. Decision making around deinfibulation was complex but for those who underwent surgery it helped to mitigate FGM impacts. Although there were examples of good practice, in general, FGM service provision was suboptimal. CONCLUSION: Deinfibulation services need to be widely advertised. Information should highlight that the procedure can be carried out at different time points, according to preference, and in a hospital by suitable HCPs. Future services should ideally be developed with survivors, to ensure that they are clinically and culturally appropriate. Guidelines would benefit from being updated to reflect the needs of survivors and to ensure consistency in provision.

Effects of mixtures of polychlorinated biphenyls (PCBs) and three organochlorine pesticides on cognitive function differ between older Mohawks at Akwesasne and older adults in NHANES.

BACKGROUND: Akwesasne Mohawks has been exposed to high concentrations of polychlorinated biphenyls (PCBs) and background levels of organochlorine pesticides, hexachlorobenzene (HCB), dichlorodiphenyl dichloroethylene (DDE), and mirex. We have previously reported relative contributions to the mixture of low- and high-chlorinated PCBs, HCB, and DDE on cognitive decrements in Mohawks of various ages. OBJECTIVE: This study examines differences in the mixture effects of PCB congener groups, HCB, DDE, and mirex on cognitive function in older Mohawks and less PCB-exposed older adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 cycles. METHODS: We used Bayesian kernel machine regression (BKMR) to evaluate the mixture effects of different PCB congener groups, HCB, DDE, and mirex on cognitive function in both populations. Models were adjusted for age, sex, education levels, and race/ethnicity focusing on individuals 60 years and older. RESULTS: Older Mohawks had 3-fold higher mean total PCB concentrations and 1.8-fold higher mirex, but slightly lower mean DDE and HCB levels than NHANES older adults. Higher mixture concentrations were significantly associated with greater cognitive decline. In older Mohawks, low- and high-chlorinated PCBs, HCB, and DDE contributed to the cognitive score decline. In contrast, score decline in older NHANES adults were primarily from high-chlorinated PCBs and DDE with a threshold dose of approximately 2.08-2.27 ng/g and 2.02-2.40 ng/g, respectively. CONCLUSION: Mixtures of PCBs and organochlorine pesticides increase the risk of cognitive decline in both older Mohawks and NHANES older adults. However, contributions to these mixture effects show significant differences. In older Mohawks, high- and low-chlorinated PCBs, DDE, and HCB are the primary contributors, while high-chlorinated PCBs and DDE are important contributors in NHANES older adults. Due to chronic heavy exposures to PCBs, older Mohawks had a significantly increased risk of cognitive decline compared to general older adults from NHANES.

Suicidal Ideation Amongst University Students During the COVID-19 Pandemic: Time Trends and Risk Factors.

OBJECTIVE: Examine time trends in suicidal ideation in post-secondary students over the first three waves of the COVID-19 pandemic in Canada and identify subpopulations of students with increased risk. METHOD: We analysed 14 months of data collected through repeated cross-sectional deployment of the World Health Organization (WHO) World Mental Health-International College Student (WMH-ICS) survey at the University of British Columbia. Estimated log odds weekly trends of 30-day suicidal ideation (yes/no) were plotted against time with adjustments for demographics using binary logistic generalized additive model (GAM). Risk factors for 30-day suicidal ideation frequency (four categories) were examined using the ordered logistic GAM, with a cubic smoothing spline for modelling time trend in obervation weeks and accounting for demographics. RESULTS: Nearly one-fifth (18.9%) of students experienced suicidal ideation in the previous 30 days. While the estimated log odds suggested that binary suicidal ideation was relatively stable across the course of the pandemic, an initial drop followed by an increasing trend was observed. Risk factors for suicidal ideation frequency during the pandemic included identifying as Chinese or as another non-Indigenous ethnic minority; experiencing current symptoms of depression or anxiety; having a history of suicidal planning or attempts; and feeling overwhelmed but unable to get help as a result of COVID-19. Older age was identified as a protective factor. CONCLUSIONS: The general university student population in our study was relatively resilient with respect to suicidal ideation during the first three waves of the pandemic, but trends indicate the possibility of delayed impact. Specific sub-populations were found to be at increased risk and should be considered for targeted support. Further analyses should be undertaken to continue monitoring suicidality trends throughout the remainder of the pandemic and beyond.

An ErbB2 splice variant lacking exon 16 drives lung carcinoma.

Lung cancer causes more deaths annually than any other malignancy. A subset of non-small cell lung cancer (NSCLC) is driven by amplification and overexpression or activating mutation of the receptor tyrosine kinase (RTK) ERBB2 In some contexts, notably breast cancer, alternative splicing of ERBB2 causes skipping of exon 16, leading to the expression of an oncogenic ERBB2 isoform (ERBB2ΔEx16) that forms constitutively active homodimers. However, the broader implications of ERBB2 alternative splicing in human cancers have not been explored. Here, we have used genomic and transcriptomic analysis to identify elevated ERBB2ΔEx16 expression in a subset of NSCLC cases, as well as splicing site mutations facilitating exon 16 skipping and deletions of exon 16 in a subset of these lung tumors and in a number of other carcinomas. Supporting the potential of ERBB2ΔEx16 as a lung cancer driver, its expression transformed immortalized lung epithelial cells while a transgenic model featuring inducible ERBB2ΔEx16 specifically in the lung epithelium rapidly developed lung adenocarcinomas following transgene induction. Collectively, these observations indicate that ERBB2ΔEx16 is a lung cancer oncogene with potential clinical importance for a proportion of patients.

"Life goes on": Perspectives on the will to live from residents of Swiss long-term care facilities.

OBJECTIVES: While there is a growing body of literature on the wish to die in older patients, there is little research about their will to live. Exploring the subjective will to live (WTL) offers valuable insights into the patients' resources and motivations, which could help improving geriatric palliative care. The aim of this study was to examine, in long-term care facilities (LTCF), residents' definitions of and factors influencing their WTL. METHODS: Twenty residents (mean age 85.8 ± 10.3 years, 70% women) of 3 Swiss LTCFs gave informed consent and participated in semi-structured interviews about their WTL. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted to identify recurrent themes (40% double coded). RESULTS: The majority of residents reported that they had not thought about the WTL. Nevertheless, they had no difficulty in describing it as innate in their lives. They spontaneously mentioned factors that contributed to their WTL, classified into 5 themes: (1) relationships - primarily with family and health professionals, secondarily with other residents; (2) living situation - the LTCF as a necessary place providing care, constant professional presence, and security, yet necessitates inconveniences such as loss of independence; (3) personality factors - positive outlook on life or spirituality; (4) engagement in routines - organized activities and individual daily routines; and (5) health status - primarily related to functional health. SIGNIFICANCE OF RESULTS: Examining WTL provides important insights into elements that are essential to take into account in planning care and promoting well-being in LTCF residents. The themes identified provide important starting points for improving life in LTCFs.

Lights, fluorescence, action-Influencing wound treatment plans including debridement of bacteria and biofilms.

High bacterial loads within chronic wounds increase the risk of infection and complication. Detection and localization of bacterial loads through point-of-care fluorescence (FL) imaging can objectively inform and support bacterial treatment decisions. This single time-point, retrospective analysis describes the treatment decisions made on 1000 chronic wounds (DFUs, VLUs, PIs, surgical wounds, burns, and others) at 211 wound-care facilities across 36 US states. Clinical assessment findings and treatment plans derived from them, as well as subsequent FL-imaging (MolecuLight®) findings and any associated treatment plan changes, were recorded for analysis. FL signals indicating elevated bacterial loads were observed in 701 wounds (70.8%), while only 293 (29.6%) showed signs/symptoms of infection. After FL-imaging, treatment plans changed in 528 wounds as follows: more extensive debridement (18.7%), more extensive hygiene (17.2%), FL-targeted debridement (17.2%), new topical therapies (10.1%), new systemic antibiotic prescriptions (9.0%), FL-guided sampling for microbiological analysis (6.2%), and changes in dressing selection (3.2%). These real-world findings of asymptomatic bacterial load/biofilm incidence, and of the frequent treatment plan changes post-imaging, are in accordance with clinical trial findings using this technology. These data, from a range of wound types, facilities, and clinician skill sets, suggest that point-of-care FL-imaging information improves bacterial infection management.

4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response.

Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages.

Weight Stigma and Mental Health in Youth: A Systematic Review and Meta-Analysis.

OBJECTIVE: Over the past two decades, there has been a steady increase in research focused on the association between weight-based stigma and mental health outcomes in children and adolescents. The present study is a systematic review and meta-analysis of the associations between weight stigma and mental health in youth. METHODS: A systematic search of PubMed, PsychInfo, and Embase databases was conducted in January 2020. Inclusion criteria included the following: (a) examined an association between weight stigma and a mental health outcome, (b) mean sample age <18 (+1 standard deviation) years, (c) written in English, and (d) peer reviewed. Forty eligible articles were identified. The moderating effects of age, sex (percent female), weight status (percent with overweight/obesity), and study quality were examined. RESULTS: Overall, meta-analytic findings using a random-effects model indicated a statistically significant moderate association between weight stigma and poorer mental health outcomes (r = .32, 95% confidence interval [0.292, 0.347], p < .001). Age and study quality each moderated the association between weight stigma and mental health. Generally, the study quality was fair to poor, with many studies lacking validated measurement of weight stigma. CONCLUSIONS: Although there was a significant association between weight stigma and mental health in youth, study quality hinders the current body of literature. Furthermore, findings highlight the lack of consideration of internalized weight stigma in child populations, the importance of using validated measures of weight stigma, and the need for increased awareness of how these associations affect populations of diverse backgrounds.

Differences in Cardiometabolic Comorbidities Between Black and White Persons Living With Multiple Sclerosis.

OBJECTIVE: To determine differences in obesity, type 2 diabetes, and hypertension in Black patients compared with White patients with multiple sclerosis (MS). DESIGN: Cross-sectional database review. SETTING: Large academic medical center research records database. PARTICIPANTS: A total of 3191 patient cases (N=3191; 77% female, 34% Black) identified by MS diagnosis within the medical record. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Diagnosis codes for type 2 diabetes and hypertension. Body mass index (BMI), race, age, and sex were collected. Analysis of variance (continuous variables) and chi-square analyses (categorical variables) were conducted to determine differences in obesity, diabetes, and hypertension between race and sex. Logistic regression was conducted to determine odds ratios (ORs) of developing diabetes and hypertension based on race, sex, BMI, and age. RESULTS: Black patients were more than twice as likely to be diagnosed as having diabetes (OR, 2.15 [95% CI, 1.70-2.72]; P<.0001) or hypertension (OR, 2.44 [95% CI, 2.05-2.91], P<.0001) compared with White patients. Sex did not present a greater likelihood of being diagnosed as having diabetes; however, men were 1.22 times more likely be diagnosed as having hypertension compared with women (95% CI, 1.01-1.49; P=.0439). Increased age and BMI were also significantly associated with likelihood of diagnosis of diabetes and hypertension (age: diabetes OR, 1.05 [95% CI, 1.04-1.06], P<.0001; hypertension OR, 1.06 [95% CI, 1.05-1.06], P<.0001; BMI: diabetes obese vs normal: OR, 2.11 [95% CI, 1.43-3.11], P=.0002; hypertension: obese vs normal: OR, 1.72 [95% CI, 1.39-2.13], P<.0001). CONCLUSIONS: Black patients with MS are significantly more likely to have cardiometabolic conditions than White patients. These conditions have been associated with poorer health outcomes for people with MS and may have some effect on the differences in MS disease course reported in Black patients.

Squash bees host high diversity and prevalence of parasites in the northeastern United States.

The squash bee Eucera (Peponapis) pruinosa is emerging as a model species to study how stressors impact solitary wild bees in North America. Here, we describe the prevalence of trypanosomes, microsporidians and mollicute bacteria in E. pruinosa and two other species, Bombus impatiens and Apis mellifera, that together comprise over 97% of the pollinator visitors of Cucurbita agroecosystems in Pennsylvania (United States). Our results indicate that all three parasite groups are commonly detected in these bee species, but E. pruinosa often exhibit higher prevalences. We further describe novel trypanosome parasites detected in E. pruinosa, however it is unknown how these parasites impact these bees. We suggest future work investigates parasite replication and infection outcomes.

Workflow Integration of Research AI Tools into a Hospital Radiology Rapid Prototyping Environment.

The field of artificial intelligence (AI) in medical imaging is undergoing explosive growth, and Radiology is a prime target for innovation. The American College of Radiology Data Science Institute has identified more than 240 specific use cases where AI could be used to improve clinical practice. In this context, thousands of potential methods are developed by research labs and industry innovators. Deploying AI tools within a clinical enterprise, even on limited retrospective evaluation, is complicated by security and privacy concerns. Thus, innovation must be weighed against the substantive resources required for local clinical evaluation. To reduce barriers to AI validation while maintaining rigorous security and privacy standards, we developed the AI Imaging Incubator. The AI Imaging Incubator serves as a DICOM storage destination within a clinical enterprise where images can be directed for novel research evaluation under Institutional Review Board approval. AI Imaging Incubator is controlled by a secure HIPAA-compliant front end and provides access to a menu of AI procedures captured within network-isolated containers. Results are served via a secure website that supports research and clinical data formats. Deployment of new AI approaches within this system is streamlined through a standardized application programming interface. This manuscript presents case studies of the AI Imaging Incubator applied to randomizing lung biopsies on chest CT, liver fat assessment on abdomen CT, and brain volumetry on head MRI.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

A Mixed-Methods Systematic Review and Synthesis of Secondary Care Interventions to Reduce Secondhand Smoke Exposure Among Children and Young People.

INTRODUCTION: Childhood secondhand smoke exposure (SHSe) is linked with increased morbidity and mortality. Hospital or secondary care contact presents a "teachable moment" to support parents to change their home smoking behaviors to reduce children's SHSe. AIMS AND METHODS: This mixed-methods review explores: (1) if existing interventions in this context are effective, (2) if they are reported in sufficient detail to be replicated, (3) the experiences of health care professionals delivering such interventions, and (4) the experiences of parents receiving such interventions. Five electronic databases and the gray literature were searched for relevant literature published and indexed January 1980 to February 2020. Fourteen papers reporting 12 studies (nine quantitative and five qualitative) were included. Aligned with the Joanna Briggs Institute method, a segregated approach was used involving independent syntheses of the quantitative and qualitative data followed by an overall mixed-methods synthesis. RESULTS: There was some evidence of effective interventions that resulted in a short-term (<6 months) reduction in children's SHSe when SHSe was subjectively measured. This was not seen in longer-term follow-up (>6 months) or when SHSe was measured objectively. Inconsistencies with reporting make replication challenging. Experiential evidence suggests a mismatch between stakeholder preferences and interventions being offered. CONCLUSIONS: The pediatric secondary care interventions included in this analysis failed to show statistically significant evidence of longer-term effectiveness to reduce children's SHSe in all but one low-quality study. There was also inadequate reporting of interventions limiting assessment of effectiveness. It offers further insights into areas to target to develop effective interventions. IMPLICATIONS: This review used rigorous methods to explore the current, global literature on how children's exposure to secondhand smoke is being tackled in secondary care. This review identified only one low-quality intervention study showing a statistically significant reduction in children's SHSe beyond 6 months. Synthesis with qualitative research identifies a mismatch between what parents want in an intervention and what has been delivered to date. Reporting quality needs to be improved to ensure that interventions can be replicated and studies conducted within the National Health Service to ensure suitability to this setting.