Relationships between nitric oxide biomarkers and physiological outcomes following dietary nitrate supplementation.

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2-]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3-, NO2-, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3- supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3--rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3--depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s-1, P = 0.03) and 0-50 ms (79 ± 99 N m s-1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2-] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3-] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3-] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3- ingestion in humans.

Decision-Making Confidence of Clinical Competency Committees for Entrustable Professional Activities.

Importance: A competency-based assessment framework using entrustable professional activities (EPAs) was endorsed by the American Board of Surgery following a 2-year feasibility pilot study. Pilot study programs' clinical competency committees (CCCs) rated residents on EPA entrustment semiannually using this newly developed assessment tool, but factors associated with their decision-making are not yet known. Objective: To identify factors associated with variation in decision-making confidence of CCCs in EPA summative entrustment decisions. Design, Setting, and Participants: This cohort study used deidentified data from the EPA Pilot Study, with participating sites at 28 general surgery residency programs, prospectively collected from July 1, 2018, to June 30, 2020. Data were analyzed from September 27, 2022, to February 15, 2023. Exposure: Microassessments of resident entrustment for pilot EPAs (gallbladder disease, inguinal hernia, right lower quadrant pain, trauma, and consultation) collected within the course of routine clinical care across four 6-month study cycles. Summative entrustment ratings were then determined by program CCCs for each study cycle. Main Outcomes and Measures: The primary outcome was CCC decision-making confidence rating (high, moderate, slight, or no confidence) for summative entrustment decisions, with a secondary outcome of number of EPA microassessments received per summative entrustment decision. Bivariate tests and mixed-effects regression modeling were used to evaluate factors associated with CCC confidence. Results: Among 565 residents receiving at least 1 EPA microassessment, 1765 summative entrustment decisions were reported. Overall, 72.5% (1279 of 1765) of summative entrustment decisions were made with moderate or high confidence. Confidence ratings increased with increasing mean number of EPA microassessments, with 1.7 (95% CI, 1.4-2.0) at no confidence, 1.9 (95% CI, 1.7-2.1) at slight confidence, 2.9 (95% CI, 2.6-3.2) at moderate confidence, and 4.1 (95% CI, 3.8-4.4) at high confidence. Increasing number of EPA microassessments was associated with increased likelihood of higher CCC confidence for all except 1 EPA phase after controlling for program effects (odds ratio range: 1.21 [95% CI, 1.07-1.37] for intraoperative EPA-4 to 2.93 [95% CI, 1.64-5.85] for postoperative EPA-2); for preoperative EPA-3, there was no association. Conclusions and Relevance: In this cohort study, the CCC confidence in EPA summative entrustment decisions increased as the number of EPA microassessments increased, and CCCs endorsed moderate to high confidence in most entrustment decisions. These findings provide early validity evidence for this novel assessment framework and may inform program practices as EPAs are implemented nationally.

Integrated Proteomics Analysis of Baseline Protein Expression in Pig Tissues.

The availability of an increasingly large amount of public proteomics data sets presents an opportunity for performing combined analyses to generate comprehensive organism-wide protein expression maps across different organisms and biological conditions. Sus scrofa, a domestic pig, is a model organism relevant for food production and for human biomedical research. Here, we reanalyzed 14 public proteomics data sets from the PRIDE database coming from pig tissues to assess baseline (without any biological perturbation) protein abundance in 14 organs, encompassing a total of 20 healthy tissues from 128 samples. The analysis involved the quantification of protein abundance in 599 mass spectrometry runs. We compared protein expression patterns among different pig organs and examined the distribution of proteins across these organs. Then, we studied how protein abundances were compared across different data sets and studied the tissue specificity of the detected proteins. Of particular interest, we conducted a comparative analysis of protein expression between pig and human tissues, revealing a high degree of correlation in protein expression among orthologs, particularly in brain, kidney, heart, and liver samples. We have integrated the protein expression results into the Expression Atlas resource for easy access and visualization of the protein expression data individually or alongside gene expression data.

Liquid Chromatography Coupled to Isotope Ratio Mass Spectrometry Expanded to Include Organic Mobile Phases.

Current commercially available liquid chromatography coupled to isotope ratio mass spectrometry systems (LC-IRMS) oxidize all eluent and thus can only operate with all-aqueous mobile phases, limiting their application to a small subset of analytes and mixtures that can be separated without organic solvents. We report a novel rotating-catalytic disc desolvation device with subsequent laser-activated photocatalytic analyte combustion to create CO2 for high precision carbon isotope ratio measurements compatible with both aqueous and organic liquid mobile phases. Sucrose, glucose, androsterone, or androsterone acetate in 20% and 50% H2O-CH3OH solutions were introduced by flow injection to the interface to IRMS for sugars and steroids, respectively. Sucrose δ13CVPDB linearity was excellent over 1-10 µg (33-655 nmol C) injections, using IRMS compatible He/1%O2 oxidation gas. The limit of precise isotope analysis (LOIA) of δ13CVPDB was 1 µg (35 nmol C) for sucrose and 10 µg (655 nmol C) for androsterone with average precisions of SD(δ13C) ± 0.8‰. Calibration was performed with and bracketed the δ13CVPDB isotope ratio range using androsterone-acetate and glucose. With further development to improve sensitivity and application to chromatography, the prototype proof-of-principle LC-IRMS shows promise to resolve a major drawback in current LC-IRMS systems and may open LC-IRMS to many more compounds than currently possible.

Joint environmental and social benefits from diversified agriculture.

Agricultural simplification continues to expand at the expense of more diverse forms of agriculture. This simplification, for example, in the form of intensively managed monocultures, poses a risk to keeping the world within safe and just Earth system boundaries. Here, we estimated how agricultural diversification simultaneously affects social and environmental outcomes. Drawing from 24 studies in 11 countries across 2655 farms, we show how five diversification strategies focusing on livestock, crops, soils, noncrop plantings, and water conservation benefit social (e.g., human well-being, yields, and food security) and environmental (e.g., biodiversity, ecosystem services, and reduced environmental externalities) outcomes. We found that applying multiple diversification strategies creates more positive outcomes than individual management strategies alone. To realize these benefits, well-designed policies are needed to incentivize the adoption of multiple diversification strategies in unison.

Socioeconomic status, alcohol use and the role of social support and neighbourhood environment among individuals meeting criteria for a mental health problem: a cross-sectional study.

PURPOSE: Indicators of socioeconomic status (SES), such as education and occupational grade, are known to be associated with alcohol use but this has not been examined among individuals with a mental health problem. This study developed latent classes of SES, their associations with alcohol use, and examined the indirect effect via social support and neighbourhood environment. METHODS: A secondary analysis of the 2014 Adult Psychiatric Morbidity Survey was conducted among participants with a mental health problem (N = 1,436). SES classes were determined using a range of indicators. Alcohol use was measured using the Alcohol Use Disorder Identification Test. Social support and neighbourhood neighbourhood environment were measured using validated questionnaires. A latent class analysis was conducted to develop SES classes. Multinomial logistic regression examined associations of SES and alcohol use. Structural equation models tested indirect effects via social support and neighbourhood environment. RESULTS: A four-class model of SES was best-fitting; "economically inactive,GCSE-level and lower educated,social renters", "intermediate/routine occupation,GCSE-level educated,mixed owner/renters", "retired, no formal education,homeowners", and "professional occupation,degree-level educated,homeowners". Compared to "professional occupation,degree-level educated, homeowners", SES classes were more likely to be non-drinkers; odds were highest for "economically inactive,GCSE-level and lower educated,social renters" (OR = 4.96,95%CI 3.10-7.93). "Retired, no formal education,homeowners" were less likely to be hazardous drinkers (OR = 0.35,95%CI 0.20-0.59). Associations between "economically inactive,GCSE-level and lower educated,social renters" and "retired, no formal education,homeowners" and non- and harmful drinking via social support and neighbourhood environment were significant. CONCLUSIONS: In contrast to the alcohol harms paradox, among individuals with a mental health problem, lower SES groups were more likely to be non-drinkers while no associations with harmful drinking were found. There is also a need to examine the alcohol harms paradox in the context of the area in which they live.

Point-of-choice kilocalorie labelling practices in large, out-of-home food businesses: a preobservational versus post observational study of labelling practices following implementation of The Calorie Labelling (Out of Home Sector) (England) Regulations 2021.

BACKGROUND AND OBJECTIVES: On 6 April 2022, the UK government implemented mandatory kilocalorie (kcal) labelling regulations for food and drink products sold in the out-of-home food sector (OHFS) in England. Previous assessments of kcal labelling practices in the UK OHFS found a low prevalence of voluntary implementation and poor compliance with labelling recommendations. This study aimed to examine changes in labelling practices preimplementation versus post implementation of mandatory labelling regulations in 2022. METHODS: In August-December 2021 (preimplementation) and August-November 2022 (post implementation), large OHFS businesses (250 or more employees) subject to labelling regulations were visited. At two time points, a researcher visited the same 117 food outlets (belonging to 90 unique businesses) across four local authorities in England. Outlets were rated for compliance with government regulations for whether kcal labelling was provided at any or all point of choice, provided for all eligible food and drink items, provided per portion for sharing items, if labelling was clear and legible and if kcal reference information was displayed. RESULTS: There was a significant increase (21% preimplementation vs 80% post implementation, OR=40.98 (95% CI 8.08 to 207.74), p<0.001) in the proportion of outlets providing any kcal labelling at point-of-choice post implementation. Only 15% of outlets met all labelling compliance criteria post implementation, with a minority of outlets not presenting labelling in a clear (33%) or legible (29%) way. CONCLUSION: The number of large businesses in the OHFS providing kcal labelling increased following the implementation of mandatory labelling regulations. However, around one-fifth of eligible outlets sampled were not providing kcal labelling 4-8 months after the regulations came into force, and the majority of businesses only partially complied with government guidance. More effective enforcement may be required to further improve kcal labelling practices in the OHFS in England. PREREGISTRATION: Study protocol and analysis strategy preregistered on Open Science Framework (https://osf.io/pfnm6/).

The extrastriate symmetry response is robust to alcohol intoxication.

Visual symmetry activates a network of regions in the extrastriate cortex and generates an event-related potential (ERP) called the sustained posterior negativity (SPN). Previous work has found that the SPN is robust to experimental manipulations of task, spatial attention, and memory load. In the current study, we investigated whether the SPN is also robust to alcohol-induced changes in mental state. A pilot experiment (N = 13) found that alcohol unexpectedly increased SPN amplitude. We followed this unexpected result with two new experiments on separate groups, using an alcohol challenge paradigm. One group completed an Oddball discrimination task (N = 26). Another group completed a Regularity discrimination task (N = 26). In both groups, participants consumed a medium dose of alcohol (0.65 g/kg body weight) and a placebo drink, in separate sessions. Alcohol reduced SPN amplitude in the Oddball task (contrary to the pilot results) but had no effect on SPN amplitude in the Regularity task. In contrast, the N1 wave was consistently dampened by alcohol in all experiments. Exploratory analysis indicated that the inconsistent effect of alcohol on SPN amplitude may be partly explained by individual differences in alcohol use. Alcohol reduced the SPN in light drinkers and increased it in heavier drinkers. Despite remaining questions, the results highlight the automaticity of symmetry processing. Symmetry still produces a large SPN response, even when participants are intoxicated, and even when symmetry is not task relevant.

The Associations among Perceived Courtesy Stigma, Health and Social Behaviours in Family Members and Friends of People Who Use Substances: An Ecological Momentary Assessment Study.

Background: The stigma and discrimination experienced by individuals with an alcohol/substance use disorder often extends to the family members and friends who provide care, which is known as courtesy stigma. This courtesy stigma can lead to isolation, poor mental health and might impact the quality-of-care these individuals provide. The aim of this study was to examine the frequency of experienced courtesy stigma/discrimination in individuals in a family support service for a loved one's substance use, and to examine any cross-sectional associations with changes in mood, health- and social-related outcomes. Methods: Thirty-six individuals (25 female) with a mean age of 51.91 years took part in an ecological momentary assessment study in which the experience of courtesy stigma/discrimination and measures of mood, health (e.g. alcohol use, nicotine use, healthy eating, sleep, physical activity) and social connections were taken 3 times per day for fourteen days. Results: Across 1029 competed assessments (compliance ∼68%), there were 122 (∼11%) reports of courtesy stigma/discrimination. The most common sources of stigma/discrimination were from family members (∼43% of occurrences) and friends (∼31% of occurrences). Experiencing this stigma/discrimination was associated with increases in alcohol and nicotine use, as well as reductions in healthy eating, physical activity, sleep, social connections, and mood. Conclusions: The experience of courtesy stigma/discrimination was common in a sample of individual's who support a loved one with alcohol or substance use disorder. These experiences are associated with changes in health and social behaviors and may lead to a poorer quality of care.

The Virtual Child.

SUMMARY: We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life.

Changing sustainable diet behaviours during the COVID-19 Pandemic: inequitable outcomes across a sociodemographically diverse sample of adults.

The objective of this study was to describe changes in sustainable dietary behaviours (those that support environmental, economic, and physical health) among a sample of US adults during the COVID-19 pandemic and to examine differences in changes by individuals' race/ethnicity and socioeconomic status. Therefore, a cross-sectional online survey study was conducted in April 2021 (N = 1,488, mean age = 42.7 (SD = 12.6)) receiving outpatient care from Michigan Medicine, the University of Michigan health system. Enrolment quotas were established to ensure a diverse sample-one-third of participants identified as African American/Black, one-third Hispanic/Latino, one-third White, and one-third low-income. Participants reported engaging in more behaviours that are supportive of a sustainable diet one year into the COVID-19 pandemic compared to before. This is particularly true regarding ecologically and economically sustaining behaviours such as taking fewer trips to the grocery store, increased use of home grocery delivery, increased cooking at home, and greater consumption of healthy foods. Not all behaviour changes promoted sustainable food systems; namely, the use of farmer's markets and Community Supported Agriculture (CSAs) declined. White and high-income participants were more likely than African American/Black, Hispanic/Latino, and low-income individuals to engage in ecologically and economically sustainable dietary behaviours during the pandemic. Meanwhile, African American/Black participants reported large increases in physical health sustainable dietary behaviours. To support the continuation of greater engagement with sustainable diets, policies that increase access to public transportation, limit the frequency with which consumers have groceries delivered, increase work-from-home options, and improve access for low-income populations should be prioritised.

Better kidney allograft survival despite higher-risk donor and recipient characteristics between 1995-2014.

BACKGROUND AND HYPOTHESIS: Advances in organ procurement, surgical techniques, immunosuppression regimens and prophylactic antibiotic therapies have dramatically improved short term kidney transplant graft failure. It is unclear how these interventions have affected longer term graft failure. It is hypothesised that graft failure has improved over the last 20 years. METHODS: Data on all first kidney transplants from 1995-2014 were extracted from the Australia and New Zealand Dialysis and Transplant Registry with follow-up as of 31 December, 2021. Primary exposure was transplant era, classified into 5-year intervals. Primary outcome was all-cause 5-year graft failure. Secondary outcomes included all-cause 10-year graft failure and cause-specific graft failure. Kaplan Meier curves and multivariable Cox Proportional Hazards Regression models were used to assess trends in all-cause graft failure. Fine-Gray subdistribution hazard models verified that changes in death rates were not biasing the Cox Proportional Hazards Regression models. Cumulative incidence functions were used to assess temporal trends in cause-specific graft failure. RESULTS: Across 10 871 kidney transplants, there was a shift towards transplanting more recipients aged over 45 years old, with more comorbidities, longer dialysis vintage, body mass index greater than 30 kg/m2 and greater human leukocyte antigen mismatches. Donor age has increased but no clear shift in donor source was observed. Compared to 1995-1999 (reference), the adjusted hazard ratio for 5-year graft failure was 0.78 (95% CI 0.67-0.91), 0.70 (95% CI 0.59-0.83) and 0.60 (95% CI 0.50-0.73) for 2000-2004, 2005-2009, and 2010-2014, respectively. Ten-year graft failure similarly reduced from 0.83 (95% CI 0.74-0.93) for 2000-04 to 0.78 (95% CI 0.68-0.89) for 2010-14, compared to 1995-99. CONCLUSION: Medium and long term all-cause graft failure has improved steadily since 1995-99. Significant reductions in graft failure due to rejection and vascular causes were observed at 5 years, and due to rejection, vascular causes, death and glomerular disease at 10 years.

Acetylation of Rec8 cohesin complexes regulates reductional chromosome segregation in meiosis.

For establishing sister chromatid cohesion and proper chromosome segregation in mitosis in fission yeast, the acetyltransferase Eso1 plays a key role. Eso1 acetylates cohesin complexes, at two conserved lysine residues K105 and K106 of the cohesin subunit Psm3. Although Eso1 also contributes to reductional chromosome segregation in meiosis, the underlying molecular mechanisms have remained elusive. Here, we purified meiosis-specific Rec8 cohesin complexes localized at centromeres and identified a new acetylation at Psm3-K1013, which largely depends on the meiotic kinetochore factor meikin (Moa1). Our molecular genetic analyses indicate that Psm3-K1013 acetylation cooperates with canonical acetylation at Psm3-K105 and K106, and plays a crucial role in establishing reductional chromosome segregation in meiosis.

I can't believe I missed that! How the fear of missing out impacts on alcohol behaviours.

BACKGROUND: The Fear of Missing Out (FoMO), which is often experienced over missing opportunities for social gains associated with drinking, has been linked to heavy episodic drinking and experiencing negative consequences. The UK Coronavirus (COVID-19)-related lockdown provided a unique context to study FoMO's ability to predict of alcohol consumption. The aim of the current study was to test if FoMO predicted alcohol consumption during a time of social restrictions. METHODS: One hundred and five UK adults (aged 18-30, 61% female) participated in a study using an ecological momentary assessment design. Surveys were completed on smartphones and assessed FoMO and drinking intentions, three time a day (morning, afternoon, evening) over three consecutive weekends (Friday, Saturday, Sunday). Alcohol consumption was recorded once per day, based on previous day consumption. RESULTS: Repeated mixed model analyses found FoMO significantly predicted quantity of alcohol consumption (b =.05, p =.01) and drinking intentions (b =.47, p <.001), but did not predict frequency of consumption. Being male (b = 2.93, p =.02) and higher intentions (b = 0.5, p <.001) predicted higher quantity of consumption. Drinking intentions was the only variable to predict frequency of consumption (b =.004, p <.001). CONCLUSIONS: The study showed FoMO can predict quantity of alcohol consumption and drinking intentions, which are linked to increased negative consequences. Future studies should assess FoMO against other predictive factors. Results provide an insight into how a social predictor influenced alcohol consumption during a time of restrictions.

Self-regulatory control processes in youths: A temporal network analysis approach.

Objective: This study aimed to better understand the temporal interrelationships among self-control, response inhibition, and anger (i.e., momentary state and rumination) on both the within- and between-person levels in male adolescents. Method: We applied temporal network analyses among 62 male adolescents with a wide range of behavioral difficulties. Self-control, momentary anger, and anger rumination were mapped by self-report measures, whereas we measured response inhibition through an ambulatory Go/No-go task (two measures a day-morning and afternoon-over a 9-day period). Results: Temporal network analysis, at the within-person level, revealed that morning measures of response inhibition, anger rumination, and self-control were related to the corresponding measure in the afternoon. More efficient response inhibition in the morning was associated with higher self-control in the afternoon. Higher anger rumination in the morning led to higher momentary anger in the afternoon. In a concurrent within-person network, higher momentary anger was reciprocally associated with lower self-control. At the between-person level, higher momentary anger was correlated to higher anger rumination, lower response inhibition, and lower self-control. Discussion: This study provides insight into the dynamic interactions among self-control, response inhibition, and anger (momentary state and rumination) in male adolescents, advancing the understanding of self-regulatory control functioning.

Inducing Circularly Polarized Single-Photon Emission via Chiral-Induced Spin Selectivity.

One of the central aims of the field of spintronics is the control of individual electron spins to effectively manage the transmission of quantized data. One well-known mechanism for controlling electronic spin transport is the chiral-induced spin-selectivity (CISS) effect in which a helical nanostructure imparts a preferential spin orientation on the electronic transport. One potential application of the CISS effect is as a transduction pathway between electronic spin and circularly polarized light within nonreciprocal photonic devices. In this work, we identify and quantify the degree of chiral-induced spin-selective electronic transport in helical polyaniline films using magnetoconductive atomic force microscopy (mcAFM). We then induce circularly polarized quantum light emission from CdSe/CdS core/shell quantum dots placed on these films, demonstrating a degree of circular polarization of up to ∼21%. Utilizing time-resolved photoluminescence microscopy, we measure the radiative lifetime difference associated with left- and right-handed circular polarizations of single emitters. These lifetime differences, in combination with Kelvin probe mapping of the variation of surface potential with magnetization of the substrate, help establish an energy level diagram describing the spin-dependent transport pathways that enable the circularly polarized photoluminescence.

Glucocorticoid prescribing in neurology.

Glucocorticoids are commonly used for neurological disorders, but they can have significant adverse effects, including adrenal insufficiency, hyperglycaemia, osteoporosis and increased infection risk. Long-term use of corticosteroids requires the prescriber to plan risk mitigation, including monitoring and often coprescribing. This article highlights the potential risks of corticosteroid prescribing and draws together up-to-date guidance with multispecialty input to clarify ways of reducing those risks. We discuss home blood glucose monitoring and consider a steroid safety checklist to promote safer steroid prescribing.

Ecological patterns and processes of temporal turnover within lung infection microbiota.

BACKGROUND: Chronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical 'one microbe, one disease' concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota. RESULTS: The lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend's rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function. CONCLUSIONS: Our work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases. Video Abstract.

The Impact of Digital Hospitals on Patient and Clinician Experience: Systematic Review and Qualitative Evidence Synthesis.

BACKGROUND: The digital transformation of health care is advancing rapidly. A well-accepted framework for health care improvement is the Quadruple Aim: improved clinician experience, improved patient experience, improved population health, and reduced health care costs. Hospitals are attempting to improve care by using digital technologies, but the effectiveness of these technologies is often only measured against cost and quality indicators, and less is known about the clinician and patient experience. OBJECTIVE: This study aims to conduct a systematic review and qualitative evidence synthesis to assess the clinician and patient experience of digital hospitals. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and ENTREQ (Enhancing the Transparency in Reporting the Synthesis of Qualitative Research) guidelines were followed. The PubMed, Embase, Scopus, CINAHL, and PsycINFO databases were searched from January 2010 to June 2022. Studies that explored multidisciplinary clinician or adult inpatient experiences of digital hospitals (with a full electronic medical record) were included. Study quality was assessed using the Mixed Methods Appraisal Tool. Data synthesis was performed narratively for quantitative studies. Qualitative evidence synthesis was performed via (1) automated machine learning text analytics using Leximancer (Leximancer Pty Ltd) and (2) researcher-led inductive synthesis to generate themes. RESULTS: A total of 61 studies (n=39, 64% quantitative; n=15, 25% qualitative; and n=7, 11% mixed methods) were included. Most studies (55/61, 90%) investigated clinician experiences, whereas few (10/61, 16%) investigated patient experiences. The study populations ranged from 8 to 3610 clinicians, 11 to 34,425 patients, and 5 to 2836 hospitals. Quantitative outcomes indicated that clinicians had a positive overall satisfaction (17/24, 71% of the studies) with digital hospitals, and most studies (11/19, 58%) reported a positive sentiment toward usability. Data accessibility was reported positively, whereas adaptation, clinician-patient interaction, and workload burnout were reported negatively. The effects of digital hospitals on patient safety and clinicians' ability to deliver patient care were mixed. The qualitative evidence synthesis of clinician experience studies (18/61, 30%) generated 7 themes: inefficient digital documentation, inconsistent data quality, disruptions to conventional health care relationships, acceptance, safety versus risk, reliance on hybrid (digital and paper) workflows, and patient data privacy. There was weak evidence of a positive association between digital hospitals and patient satisfaction scores. CONCLUSIONS: Clinicians' experience of digital hospitals appears positive according to high-level indicators (eg, overall satisfaction and data accessibility), but the qualitative evidence synthesis revealed substantive tensions. There is insufficient evidence to draw a definitive conclusion on the patient experience within digital hospitals, but indications appear positive or agnostic. Future research must prioritize equitable investigation and definition of the digital clinician and patient experience to achieve the Quadruple Aim of health care.