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In this study, we investigate atmospheric new particle formation (NPF) across 65 d in the Bolivian central Andes at two locations: the mountaintop Chacaltaya station (CHC, 5.2 km above sea level) and an urban site in El Alto–La Paz (EAC), 19 km apart and at 1.1 km lower altitude. We classified the days into four categories based on the intensity of NPF, determined by the daily maximum concentration of 4–7 nm particles: (1) high at both sites, (2) medium at both, (3) high at EAC but low at CHC, and (4) low at both. These categories were then named after their emergent and most prominent characteristics: (1) Intense-NPF, (2) Polluted, (3) Volcanic, and (4) Cloudy. This classification was premised on the assumption that similar NPF intensities imply similar atmospheric processes. Our findings show significant differences across the categories in terms of particle size and volume, sulfuric acid concentration, aerosol compositions, pollution levels, meteorological conditions, and air mass origins. Specifically, intense NPF events (1) increased Aitken mode particle concentrations (14–100 nm) significantly on 28 % of the days when air masses passed over the Altiplano. At CHC, larger Aitken mode particle concentrations (40–100 nm) increased from 1.1 × 103 cm−3 (background) to 6.2 × 103 cm−3, and this is very likely linked to the ongoing NPF process. High pollution levels from urban emissions on 24 % of the days (2) were found to interrupt particle growth at CHC and diminish nucleation at EAC. Meanwhile, on 14 % of the days, high concentrations of sulfate and large particle volumes (3) were observed, correlating with significant influences from air masses originating from the actively degassing Sabancaya volcano and a depletion of positive 2–4 nm ions at CHC but not at EAC. During these days, reduced NPF intensity was observed at CHC but not at EAC. Lastly, on 34 % of the days, overcast conditions (4) were associated with low formation rates and air masses originating from the lowlands east of the stations. In all cases, event initiation (∼ 09:00 LT) generally occurred about half an hour earlier at CHC than at EAC and was likely modulated by the daily solar cycle. CHC at dawn is in an air mass representative of the regional residual layer with minimal local surface influence due to the barren landscape. As the day progresses, upslope winds bring in air masses affected by surface emissions from lower altitudes, which may include anthropogenic or biogenic sources. This influence likely develops gradually, eventually creating the right conditions for an NPF event to start. At EAC, the start of NPF was linked to the rapid growth of the boundary layer, which favored the entrainment of air masses from above. The study highlights the role of NPF in modifying atmospheric particles and underscores the varying impacts of urban versus mountain top environments on particle formation processes in the Andean region.

Abstract Maximal isometric contraction time (MICT) is critical for most motor tasks and depends on skeletal muscle blood flow at

Abstract Elevated high-sensitivity cardiac troponin-T (hs-cTnT) is associated with mortality in older adults. However, little is known about the implications of changes over time. We investigated hs-cTnT 3-year change and its association with subsequent mortality in the Activity and Function in the Elderly Study. Participants with baseline and follow-up hs-cTnT 14 ng/L (n = 74). Cox-proportional hazards models evaluated the association with mortality adjusting for age, sex, education, cardiovascular disease, chronic kidney disease, number of medications, hs-CRP, and NT-proBNP. Among 745 participants (median age 75.9 years, 58.9% male) we observed 98 deaths (median follow-up 4.8 years). G1 had the lowest mortality rate (MR) (5.2 per 1000 person-years). The highest MR were observed by follow-up ≥ 14 ng/L: G3: 95.4 and G6: 100.4 per 1000 person-years, with an adjusted hazard ratio of 5.22 [95% CI 1.46, 18.65] and 3.40 [95% CI 1.02, 11.34], respectively. Hs-cTnT trajectories could help to identify older adults with a high mortality risk even after further adjustment including hs-CRP and NT-proBNP.

Abstract Background As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those subjects who responded to treatment, to build a more precise Phase 3 trial design for further investigation in likely responders. Results Subjects with mtDNA pathogenic variants or single large-scale mtDNA deletions represented 74% of the MMPOWER-3 population, with 70% in the mtDNA cohort having either single large-scale mtDNA deletions or MT-TL1 pathogenic variants. Most subjects in the nDNA cohort had pathogenic variants in genes required for mtDNA maintenance (mtDNA replisome), the majority of which were in POLG and TWNK. The mtDNA replisome post-hoc cohort displayed an improvement on the 6MWT, trending towards significant, in the elamipretide group when compared with placebo (25.2 ± 8.7 m versus 2.0 ± 8.6 m for placebo group; p = 0.06). The 6MWT results at week 24 in subjects with replisome variants showed a significant change in the elamipretide group subjects who had chronic progressive external ophthalmoplegia (CPEO) (37.3 ± 9.5 m versus − 8.0 ± 10.7 m for the placebo group; p = 0.0024). Pharmacokinetic (exposure–response) analyses in the nDNA cohort showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement. Conclusions Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders. Classification of evidence Class I ClinicalTrials.gov identifier NCT03323749

BackgroundHealth care systems and the nursing profession worldwide are being transformed by technology and digitalization. Nurses acquire digital competence through their own experience in daily practice, but also from education and training; nursing education providers thus play an important role. While nursing education providers have some level of digital competence, there is a need for ongoing training and support for them to develop more advanced skills and effectively integrate technology into their teaching. ObjectiveThis study aims to develop a needs-based support program for nursing education providers to foster digital competencies and to test this intervention. MethodsWe used a design-based research approach, incorporating iterative development with expert consultation to create and evaluate a support program for nursing education providers. Focus groups were conducted online to assess needs, and thematic content analysis was used to derive key insights. The support program was then refined through expert feedback and subjected to a feasibility and satisfaction test, with participant evaluations analyzed descriptively. ResultsSix main categories emerged from the focus groups, highlighting key areas, including the use of digital technology, ongoing support needs, and the current state of digitalization in nursing education. The support program was developed based on these findings, with expert validation leading to adjustments in timing, content prioritization, and platform integration. Preliminary testing showed good overall satisfaction with the support program, although participants suggested improvements in content relevance and digital platform usability. ConclusionsAlthough the feasibility test showed high satisfaction with the support program, low participation rates and limited perceived knowledge gain were major concerns. The results suggest that while the program was well received, further refinements, including a focus on competency-based approaches and addressing workplace barriers, are needed to increase participation and effectiveness of such interventions. The findings of this research can be used as a basis for the development of similar programs in other educational and health care contexts.

ABSTRACT This case series presents the use of elamipretide in two patients with different progressive mitochondrial disorders (chronic progressive external ophthalmoplegia [CPEO] plus and neuropathy, ataxia, and retinitis pigmentosa [NARP] syndrome) characterized by ophthalmic traits. Elamipretide was well tolerated and both patients demonstrated improvement in symptoms while on therapy.

Abstract Background The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (IMI2-853966) aimed to develop tools to establish integrated research platforms (IRP) for conducting adaptive-design trials in various diseases, including metabolic-dysfunction associated steatohepatitis (MASH). One essential component of a successful MASH IRP is a robust and reliable Clinical Research Network (CRN). Herein, we outline the required elements and anticipated steps to set-up such a CRN. Methods We identified European clinical research sites that could potentially serve as the foundation for MASH IRP and a CRN. A survey was sent to sites to assess their interest in joining a CRN, their familiarity with platform trials, and their capacity to participate in a future MASH IRP. Results A total of 141 investigators were invited to participate in the survey, and 40% responded. More than half of the answers (52%) identify MASH with advanced fibrosis (F3-4) as the subpopulation with the greatest unmet need. Regarding the difficulty in identifying candidates for trials, 65% find it is moderately difficult and 30% very difficult. Most respondents (94%) believe that a platform trial could offer substantial benefits to patients. Nearly all researchers express interest in participating in a platform trial (78%), with 22% indicating their interest would be contingent on initial industry funding. Conclusion While preliminary, our findings on responding sites are encouraging for the potential establishment of a CRN for a MASH IRP. However, funding schemes and sustainability strategies to provide proof-of-platform in MASH seem key in the short-term scenario.

Abstract Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

Abstract Background Home treatment in child and adolescent psychiatry offers an alternative to conventional inpatient treatment by involving the patient’s family, school, and peers more directly in therapy. Although several reviews have summarised existing home treatment programmes, evidence of their effectiveness remains limited and data synthesis is lacking. Methods We conducted a meta-analysis on the effectiveness of home treatment compared with inpatient treatment in child and adolescent psychiatry, based on a systematic search of four databases (PubMed, CINAHL, PsychINFO, Embase). Primary outcomes were psychosocial functioning and psychopathology. Additional outcomes included treatment satisfaction, duration, costs, and readmission rates. Group differences were expressed as standardised mean differences (SMD) in change scores. We used three-level random-effects meta-analysis and meta-regression and conducted both superiority and non-inferiority testing. Results We included 30 studies from 13 non-overlapping samples, providing data from 1795 individuals (mean age: 11.95 ± 2.33 years; 42.5% female). We found no significant differences between home and inpatient treatment for postline psychosocial functioning (SMD = 0.05 [− 0.18; 0.30], p = 0.68, I 2 = 98.0%) and psychopathology (SMD = 0.10 [− 0.17; 0.37], p = 0.44, I 2 = 98.3%). Similar results were observed from follow-up data and non-inferiority testing. Meta-regression showed better outcomes for patient groups with higher levels of psychopathology at baseline and favoured home treatment over inpatient treatment when only randomised controlled trials were considered. Conclusions This meta-analysis found no evidence that home treatment is less effective than conventional inpatient treatment, highlighting its potential as an effective alternative in child and adolescent psychiatry. The generalisability of these findings is reduced by limitations in the existing literature, and further research is needed to better understand which patients benefit most from home treatment. Trial registration Registered at PROSPERO (CRD42020177558), July 5, 2020.

Abstract The rapid transformation of sensory inputs into meaningful neural representations is critical to adaptive human behaviour. While non-invasive neuroimaging methods are the de-facto method for investigating neural representations, they remain expensive, not widely available, time-consuming, and restrictive. Here we show that movement trajectories can be used to measure emerging neural representations with fine temporal resolution. By combining online computer mouse-tracking and publicly available neuroimaging data via representational similarity analysis (RSA), we show that movement trajectories track the unfolding of stimulus- and category-wise neural representations along key dimensions of the human visual system. We demonstrate that time-resolved representational structures derived from movement trajectories overlap with those derived from M/EEG (albeit delayed) and those derived from fMRI in functionally-relevant brain areas. Our findings highlight the richness of movement trajectories and the power of the RSA framework to reveal and compare their information content, opening new avenues to better understand human perception.

Key Clinical Message This case report presents a progressively declining 17‐year‐old patient with membrane protein‐associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6‐minute walk test and 5 times sit‐to‐stand test during elamipretide treatment.

Introduction Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.Methods and analysis SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2–6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.Ethics and dissemination The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.Trial registration number NCT04680910.

Abstract It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis. Continental/subcontinental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov–Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. We observed no reduction in overall DY associated with any genetic ancestry (African, Native American, East Asian, European, Middle Eastern, South Asian). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.

Abstract Under what conditions do citizens support coercive public policies? Although recent research suggests that people prefer policies that preserve freedom of choice, such as behavioural nudges, many citizens accepted stringent policy interventions like fines and mandates to promote vaccination during the COVID-19 pandemic—a pattern that may be linked to the unusually high effectiveness of COVID-19 vaccines. We conducted a large online survey experiment (N = 42,417) in the Group of Seven (G-7) countries investigating the relationship between a policy’s effectiveness and public support for stringent policies. Our results indicate that public support for stringent vaccination policies increases as vaccine effectiveness increases, but at a modest scale. This relationship flattens at higher levels of vaccine effectiveness. These results suggest that intervention effectiveness can be a significant predictor of support for coercive policies but only up to some threshold of effectiveness.

Abstract Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case–control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case–control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.

Abstract The anatomically complex and often spatially restricted conditions of anastomosis in the head and neck region cannot be adequately reproduced by training exercises on current ex vivo or small animal models. With the development of a Realistic Anatomical Condition Experience (RACE) model, complex spatial-anatomical surgical areas and the associated intraoperative complexities could be transferred into a realistic training situation in head and neck surgery. The RACE model is based on a stereolithography file generated by intraoperative use of a three-dimensional surface scanner after neck dissection and before microvascular anastomosis. Modelling of the acquired STL file using three-dimensional processing software led to the model’s final design. As a result, we have successfully created an economical, sustainable and realistic model for microsurgical education and provide a step-by-step workflow that can be used in surgical and general medical education to replicate and establish comparable models. We provide an open source stereolithography file of the head-and-neck RACE model for printing for educational purposes. Once implemented in other fields of surgery and general medicine, RACE models could mark a shift in medical education as a whole, away from traditional teaching principles and towards the use of realistic and individualised simulators.

Objective:Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer.Materials and Methods:Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated.Results:Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups.Conclusion:Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

Abstract Background Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes. Objective To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA. Methods The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR. Results Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767). Conclusions The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA.

Abstract Background Pandemic-induced restrictions forced curriculum transformation from on-site education to virtual learning options. This report describes this transition, the challenge of creating technology-enhanced learning for hands-on psychomotor skills teaching in physiotherapy, and students’ evaluations of the new technology-enhanced learning approach in Complex Decongestive Physiotherapy. Methods On-site theoretical background lectures were replaced with e-learning sessions. Faculty hands-on skills demonstrations for the entire class were replaced with video-recorded demonstrations. Videos included verbal and written instructions and were complemented with checklists guiding the students, training in pairs, through their learning tasks. A cross-sectional observational survey for teaching quality evaluated this new technology-enhanced learning approach and assessed students’ preference for traditional or video-based hands-on skills learning. Results Survey return rate was > 50% (46 participating students). Teaching quality was rated between 1.5 ± 0.5 and 1.8 ± 0.4 (Likert scale from − 2 to + 2). Most students (66.7%) preferred the new approach. They appreciated for example that videos were available all the time, enabling self-paced learning, providing an equally good view on skills demonstrations, and the convenience to be able to rewind, re-view, and use speed adjustment options. Conclusions Students preferred the new video-based learning of skills for Complex Decongestive Physiotherapy. Because in-class live skills demonstrations were omitted, faculty had more time to provide individual feedback and answer questions. The shift from teacher- to student-centered learning enabled students to control their own learning pace. The innovative program was maintained after pandemic-induced restrictions were lifted. The success of this approach should be tested in other physiotherapy settings and different educational institutions.

Introduction Lifelong learning is the foundation for professionals to maintain competence and proficiency in several aspects of economy and medicine. Until now, there is no evidence of overconfidence (the belief to be better than others or tested) and clinical tribalism (the belief that one’s own group outperforms others) in the specialty of health economics. We investigated the hypothesis of overconfidence effects and their relation to learning motivation and motivational patterns in healthcare providers regarding healthcare economics.Methods We conducted a national convenience online survey of 116 healthcare workers recruited from social and personal networks to detect overconfidence effects and clinical tribalism and to assess learning motivation. Instruments included self-assessments for five learning dimensions (factual knowledge, skills, attitude, problem-solving and behaviour) and a four-item situational motivation scale. The analysis comprised paired t-tests, correlation analyses and two-step cluster analyses.Results We detected overplacement, overestimation and signs of clinical tribalism. Responders in the physician subgroup rated themselves superior to colleagues and that their professional group was superior to other professions. Participants being educators in other competencies showed high overconfidence in health economics. We detected two groups of learners: overconfident but motivated persons and overconfident and unmotivated learners. Learning motivation did not correlate with overconfidence effects.Discussion We could show the presence of overconfidence in health economics, which is consistent with studies in healthcare and the economy. The subjective perception of some medical educators, being role models to students and having a superior ‘attitude’ (eg, morality) concerning the economy may foster prejudice against economists as students might believe them. It also may aggravate moral distress and disrupts interactions between healthcare providers managers and leaders. Considering the study’s limitations, lifelong interprofessional and reflective training and train-the-trainer programmes may be mandatory to address the effects.

Abstract Background Due to the asymptomatic nature of the early stages, chronic kidney disease (CKD) is usually diagnosed at late stages and lacks targeted therapy, highlighting the need for new biomarkers to better understand its pathophysiology and to be used for early diagnosis and therapeutic targets. Given the close relationship between CKD and cardiovascular disease (CVD), we investigated the associations of 233 CVD- and inflammation-related plasma proteins with kidney function decline and aimed to assess whether the observed associations are causal. Methods We included 1140 participants, aged 55–74 years at baseline, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort study, with a median follow-up time of 13.4 years and 2 follow-up visits. We measured 233 plasma proteins using a proximity extension assay at baseline. In the discovery analysis, linear regression models were used to estimate the associations of 233 proteins with the annual rate of change in creatinine-based estimated glomerular filtration rate (eGFRcr). We further investigated the association of eGFRcr-associated proteins with the annual rate of change in cystatin C-based eGFR (eGFRcys) and eGFRcr-based incident CKD. Two-sample Mendelian randomization was used to infer causality. Results In the fully adjusted model, 66 out of 233 proteins were inversely associated with the annual rate of change in eGFRcr, indicating that higher baseline protein levels were associated with faster eGFRcr decline. Among these 66 proteins, 21 proteins were associated with both the annual rate of change in eGFRcys and incident CKD. Mendelian randomization analyses on these 21 proteins suggest a potential causal association of higher tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) level with eGFR decline. Conclusions We reported 21 proteins associated with kidney function decline and incident CKD and provided preliminary evidence suggesting a potential causal association between TNFRSF11A and kidney function decline. Further Mendelian randomization studies are needed to establish a conclusive causal association.

Abstract The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated. The CLEARER algorithm was trained on six model organisms: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and employed to identify essential genes in An. gambiae. Of the 10,426 genes in An. gambiae, 1,946 genes (18.7%) were predicted to be Cellular Essential Genes (CEGs), 1716 (16.5%) to be Organism Essential Genes (OEGs), and 852 genes (8.2%) to be essential as both OEGs and CEGs. RNA interference (RNAi) was used to validate the top three highly expressed non-ribosomal predictions as probable vector control targets, by determining the effect of these genes on the survival of An. gambiae G3 mosquitoes. In addition, the effect of knockdown of arginase (AGAP008783) on Plasmodium berghei infection in mosquitoes was evaluated, an enzyme we computationally inferred earlier to be essential based on chokepoint analysis. Arginase and the top three genes, AGAP007406 (Elongation factor 1-alpha, Elf1), AGAP002076 (Heat shock 70kDa protein 1/8, HSP), AGAP009441 (Elongation factor 2, Elf2), had knockdown efficiencies of 91%, 75%, 63%, and 61%, respectively. While knockdown of HSP or Elf2 significantly reduced longevity of the mosquitoes (p

Abstract Escherichia coli ST1485 strains belong to the clinically important phylogroup F and have disseminated worldwide in humans, animals, and the environment. Here, we elucidated the pathogenome of a global collection of E. coli ST1485 isolates from diverse sources retrieved from public databases and a high-quality sequenced complete genome of colistin-resistant E. coli strain CFSAN061771 isolated from raw milk cheese which designated as a reference strain. CFSAN061771 belongs to O83:H42-ST1485 pathotype and carries a conjugative ColV plasmid, pCFSAN061771_01, combining extraintestinal virulence genes (ompt, sitA, iroN, etsC, traT, cvaC, hylF, iss, tsh, mchf, iucC, iutA) with a multidrug resistance island (bla TEM-1, aph(6)-Id, aph(3″)-Ib, sul2, dfrA14). Comparative genomic analysis revealed a high frequency of pCFSAN061771_01-like plasmids in E. coli ST1485. A notable evolutionary genetic event in E. coli ST1485 strains is the acquisition of a pCFSAN061771_02-like plasmid, which confers resistance to several antimicrobials, tellurium, and quaternary ammonium compounds. The identical virulence and antibiotic resistance profiles identified in some human and animal strains are worrisome. This is the first study to emphasize the significance of E. coli ST1485 as a global high-risk virulent and multidrug-resistant clone with zoonotic potential.

Objectives The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs.Methods A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with

Maternal decidual CD8+ T cells must integrate the antithetical demands of providing immunity to infection while maintaining immune tolerance for fetal and placental antigens. Human decidual CD8+ T cells were shown to be highly differentiated memory T cells with mixed signatures of dysfunction, activation, and effector function. However, no information is present on how specificity for microbial or fetal antigens relates to their function or dysfunction. In addition, a key question, whether decidual CD8+ T cells include unique tissue-resident memory T cells (Trm) or also effector memory T cell (Tem) types shared with peripheral blood populations, is unknown. Here, high-dimensional flow cytometry of decidual and blood CD8+ T cells identified 2 Tem populations shared in blood and decidua and 9 functionally distinct Trm clusters uniquely found in decidua. Interestingly, fetus- and virus-specific decidual CD8+ Trm cells had similar features of inhibition and cytotoxicity, with no significant differences in their expression of activation, inhibitory, and cytotoxic molecules, suggesting that not all fetus-specific CD8+ T cell responses are suppressed at the maternal-fetal interface. Understanding how decidual CD8+ T cell specificity relates to their function and tissue residency is crucial in advancing understanding of their contribution to placental inflammation and control of congenital infections.

Across the lifespan, individuals frequently choose between exploiting known rewarding options or exploring unknown alternatives. A large body of work has suggested that children may explore more than adults. However, because novelty and reward uncertainty are often correlated, it is unclear how they differentially influence decision-making across development. Here, children, adolescents, and adults (ages 8–27 years, N = 122) completed an adapted version of a recently developed value-guided decision-making task that decouples novelty and uncertainty. In line with prior studies, we found that exploration decreased with increasing age. Critically, participants of all ages demonstrated a similar bias to select choice options with greater novelty, whereas aversion to reward uncertainty increased into adulthood. Computational modeling of participant choices revealed that whereas adolescents and adults demonstrated attenuated uncertainty aversion for more novel choice options, children’s choices were not influenced by reward uncertainty.

Abstract Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. We analyzed the association between time from recognition of fever to start of antibiotics (TTA) and SRE (death, admission to intensive care unit, severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation with FN. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. TTA (median, 120 min; interquartile range, 49–180 min) was not associated with SRE, with a trend for less SREs in episodes with longer TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. In conclusion, TTA was unrelated to poor clinical outcome in pediatric patients with FN presenting without severe disease. We saw strong evidence for triage bias which could only be partially adjusted.

Key Clinical Message Nonspecific symptoms such as pleuritic or pericardial chest pain in cardiovascular implantable electronic devices patients, even with unremarkable ECG or device parameters, should always raise suspicion of electrode perforation, regardless of how long ago the implantation was performed. Abstract We report the successful percutaneous management of a 77‐year‐old woman who had a dual‐chamber pacemaker implanted more than 1 year ago and presented with pericarditis pain and compensated pericardial hemorrhagic tamponade. The symptoms were due to very late acute perforation of the atrial lead. This report is intended to raise awareness of procedure‐related complications in the large group of cardiovascular implantable electronic device patients. Pleuritic or pericardial pain in these patients should raise suspicion of electrode perforation, as the risk of perforation is not restricted to the period immediately after implantation and a lifelong risk cannot apparently be excluded.

BackgroundSame-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population.Methods and findingsWe conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA ConclusionsIn patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes.Trial registrationThis study is registered with ClinicalTrials.gov NCT03154320.

Abstract The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington’s disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases. Trial registration: NCT04698551_date of first registration: 07/01/2021.

Abstract Honey bees are vital pollinators and can be used to monitor the landscape. Consequently, interest in mounting technologies onto bees to track foraging behaviors is increasing. The barrier to entry is steep, in part because the methodology for fastening tags to bees, and the success rates, are often missing from publications. We tested six factors suspected to influence the presence and tag retention rates of nurse honey bees after their introduction to hives, and followed bees until foraging age. We also compared reintroducing foragers to their maternal colony using the best method for nurse bees to releasing them in front of their maternal hive and allowing them to fly back unaided. Nurses were most likely to be present in the hive with their tag still attached when introduced using an introduction cage at night. Glue type was important, but may further be influenced by tag material. Foragers were most likely to be present with a tag attached if released in front of their colony. Preparation and introduction techniques influence the likelihood of tagged honey bee survival and of the tags remaining attached, which should be considered when executing honey bee tagging and tracking experiments.

Abstract Quantum information processing requires fast manipulations of quantum systems in order to overcome dissipative effects. We propose a method to accelerate quantum dynamics and obtain a target state in a shorter time relative to unmodified dynamics, and apply the theory to a system consisting of two linearly coupled qubits. We extend the technique to accelerate quantum adiabatic evolution in order to rapidly generate a desired target state, thereby realizing a shortcut to adiabaticity. Further, we address experimental limitations to the rate of change of control parameters for quantum devices which often limit one’s ability to generate a desired target state with high fidelity. We show that an initial state following decelerated dynamics can reach a target state while varying control parameters more slowly, enabling more experimentally feasible driving schemes.

Abstract Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

The use of contrast-enhanced ultrasound (CEUS) has expanded over the past decade to include a variety of diagnostic and therapeutic applications. These include urgent clinical situations that require timely diagnosis and subsequent treatment. With the introduction of microbubble ultrasound contrast agents (UCAs), CEUS provides increased sensitivity and specificity over conventional ultrasound. Within the trauma setting, CEUS benefits include point of care imaging and an ability to monitor perfusion in real-time. Additionally, UCAs are non-nephrotoxic, and can be used when contrast enhanced CT is contraindicated. In this review, we discuss recent advancements of CEUS within trauma settings.

Abstract Autoantibodies are present in healthy individuals and altered in chronic diseases. We used repeated samples collected from participants in the NYU Women’s Health Study to assess autoantibody reproducibility and repertoire stability over a one-year period using the HuProt array. We included two samples collected one year apart from each of 46 healthy women (92 samples). We also included eight blinded replicate samples to assess laboratory reproducibility. A total of 21,211 IgG and IgM autoantibodies were interrogated. Of those, 86% of IgG (n = 18,303) and 34% of IgM (n = 7,242) autoantibodies showed adequate lab reproducibility (coefficient of variation [CV] 0.8). Temporal reproducibility was lower after using quantile normalization suggesting that batch variability was not an important source of error, and that normalization removed some informative biological information. To our knowledge this study is the largest in terms of sample size and autoantibody numbers to assess autoantibody reproducibility in healthy women. The results suggest that for many autoantibodies a single measurement may be used to rank individuals in studies of autoantibodies as etiologic markers of disease.

Abstract Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

Introduction Gestational diabetes mellitus (GDM) is one of the most common health complications during pregnancy. Medical nutrition therapy is the mainstay of treatment for GDM, however, there is no current consensus on optimal dietary approaches to prevent or control hyperglycaemia in pregnancy. The aim of this systematic review is to assess the relationships between plant-based dietary patterns, plant foods and botanical dietary supplements with GDM and maternal glycaemic biomarkers.Methods and analysis A predefined search strategy was used on 16 June 2021, to search PubMed, Embase and CINAHL Plus with Full Text (EBSCOhost), as well as ClinicalTrials.gov, for studies published as original articles in English. Articles will be included if they are human observational studies or clinical trials and will be excluded if they are review articles or conference abstracts. We will use Cochrane’s risk of bias tools for interventions that are parallel arm (Risk of Bias tool for randomised trials version 2 (RoB 2)) and single arm, non-randomised intervention studies (Risk of Bias In Non-randomised Studies-of Interventions (ROBINS-I)). For observational, case–control and cross-sectional studies, we will use the National Heart, Lung and Blood Institute’s quality assessment tools. Data will be synthesised in a narrative format describing significant results as well as presenting the results of the quality assessment of studies.Ethics and dissemination This systematic review does not require ethical approval as primary data will not be collected. The review will be published in a peer-reviewed journal and disseminated electronically and in print.PROSPERO registration number CRD42022306915.

Skeletal muscles are a highly structured tissue responsible for movement and metabolic regulation, which can be broadly subdivided into fast and slow twitch muscles with each type expressing common as well as specific sets of proteins. Congenital myopathies are a group of muscle diseases leading to a weak muscle phenotype caused by mutations in a number of genes including RYR1. Patients carrying recessive RYR1 mutations usually present from birth and are generally more severely affected, showing preferential involvement of fast twitch muscles as well as extraocular and facial muscles. In order to gain more insight into the pathophysiology of recessive RYR1-congential myopathies, we performed relative and absolute quantitative proteomic analysis of skeletal muscles from wild-type and transgenic mice carrying p.Q1970fsX16 and p.A4329D RyR1 mutations which were identified in a child with a severe congenital myopathy. Our in-depth proteomic analysis shows that recessive RYR1 mutations not only decrease the content of RyR1 protein in muscle, but change the expression of 1130, 753, and 967 proteins EDL, soleus and extraocular muscles, respectively. Specifically, recessive RYR1 mutations affect the expression level of proteins involved in calcium signaling, extracellular matrix, metabolism and ER protein quality control. This study also reveals the stoichiometry of major proteins involved in excitation contraction coupling and identifies novel potential pharmacological targets to treat RyR1-related congenital myopathies.

Introduction: Food insecurity (FI) has been associated with adverse health outcomes and increased healthcare expenditures. Many families experienced reduced access to food during the coronavirus disease 2019 (COVID-19) pandemic. A 2019 study revealed that the pre-pandemic prevalence of FI at an urban, tertiary care hospital’s emergency department (ED) was 35.3%. We sought to evaluate whether the prevalence of FI in the same ED patient population increased during the COVID-19 pandemic. Methods: We performed a single-center, observational, survey-based study. Surveys assessing for FI were administered to clinically stable patients presenting to the ED over 25 consecutive weekdays from November–December 2020. Results: Of 777 eligible patients, 379 (48.8%) were enrolled; 158 (41.7%) screened positive for FI. During the pandemic, there was a 18.1% relative increase (or 6.4% absolute increase) in the prevalence of FI in this population (P=0.040; OR=1.309, 95% CI 1.012–1.693). The majority (52.9%) of food-insecure subjects reported reduced access to food due to the pandemic. The most common perceived barriers to access to food were reduced food availability at grocery stores (31%), social distancing guidelines (26.5%), and reduced income (19.6%). Conclusion: Our findings suggest that nearly half of the clinically stable patients who presented to our urban ED during the pandemic experienced food insecurity. The prevalence of FI in our hospital’s ED patient population increased by 6.4% during the pandemic. Emergency physicians should be aware of rising FI in their patient population so that they may better support patients who must choose between purchasing food and purchasing prescribed medications.

Introduction Older people in need of home care are at risk of declining oral health as their visits to dentists are becoming less frequent due to restricted mobility. There is increasing evidence that poor oral health and systemic diseases are closely associated, for example, in cardiological, metabolic or neurodegenerative conditions. Thus, Interaction of Systemic Morbidity and Oral Health in Ambulatory Patients in Need of Home Care (InSEMaP) is investigating the need, provision and utilisation of oral healthcare, systemic morbidity and clinical status of the oral cavity in older people.Methods and analysis InSEMaP consists of four subprojects (SP), all involving the target population of older people in need of home care. In SP1 part a, a sample is surveyed using a self-report questionnaire. In SP1 part b, stakeholders (general practitioners, dentists, medical assistants, family and professional caregivers) are interviewed regarding barriers and facilitators using focus groups and personal interviews. In SP2, a retrospective cohort study, health insurance claims data are examined to investigate the utilisation of oral healthcare, its association with systemic morbidity and healthcare costs. In SP3, a clinical observational study will assess the oral health of participants by a dentist’s visit at home. SP4 synthesises the results of SP1, SP2 and SP3 to develop integrated clinical pathways, identifying strategies to uphold oral healthcare in older people. In assessing and evaluating the process of oral healthcare, and its associated systemic morbidity, InSEMaP aims to improve general healthcare across the sector boundary of dental and general practitioner care.Ethics and dissemination Ethics approval was obtained from the Institutional Review Board of the Hamburg Medical Chamber (approval number: 2021-100715-BO-ff). The results of this study will be disseminated through conference presentations and publications in peer-reviewed journals. An expert advisory board to support the InSEMaP study group will be established.Trial registration number German Clinical Trials Register: DRKS00027020.

Abstract The anatomy and even existence of a common tendinous origin of the extraocular eye muscles, or annulus of Zinn, has widely been debated in anatomical literature. This study explored the anatomical origins of the recti muscles, their course into the orbit and the dural connections of the common tendinous origin with the skull base. Twenty orbits of ten adult human cadavers were dissected. The orbital apex and its dural connections were photographed. Histological examination of apical specimens was performed. In all cadavers, extraocular muscles were observed to have a common tendinous origin at the orbital apex, continuous with dural connections extending into the skull base. Accessory slips of the medial rectus were observed across all cadavers. Dual heads of the lateral rectus were observed in fourteen orbits of seven cadavers. The origin of the levator palpebrae superioris appeared to be contiguous with the superior rectus at the common tendinous origin in all but one cadaver. These results support the existence of a common tendinous origin of the extraocular muscles, that is continuous with the skull base dura. In addition, they support the existence of variations in orbital anatomy including dual or accessory muscle slips of the extraocular muscles.

Abstract The concept of progressive fibrosing interstitial lung disease (PF-ILD) has recently emerged. However, real-life proportion of PF-ILDs outside IPF is still hard to evaluate. Therefore, we sought to estimate the proportion of PF-ILD in our ILD cohort. We also determined the proportion of ILD subtypes within PF-ILD and investigated factors associated with PF-ILDs. Finally, we quantified interobserver agreement between radiologists for the assessment of fibrosis. We reviewed the files of ILD patients discussed in multidisciplinary discussion between January 1st 2017 and December 31st 2019. Clinical data, pulmonary function tests (PFTs) and high-resolution computed tomography (HRCTs) were centrally reviewed. Fibrosis was defined as the presence of traction bronchiectasis, reticulations with/out honeycombing. Progression was defined as a relative forced vital capacity (FVC) decline of ≥ 10% in ≤ 24 months or 5%

Alliance ruptures of the withdrawal type are prevalent in adolescents with borderline personality disorder (BPD). Longer speech pauses are negatively perceived by these patients. Safran and Muran's rupture model is promising but its application is very work intensive. This workload makes research costly and limits clinical usage. We hypothesised that pauses can be used to automatically detect one of the markers of the rupture model i.e. the minimal response marker. Additionally, the association of withdrawal ruptures with pauses was investigated. A total of 516 ruptures occurring in 242 psychotherapy sessions collected in 22 psychotherapies of adolescent patients with BPD and subthreshold BPD were investigated. Trained observers detected ruptures based on video and audio recordings. In contrast, pauses were automatically marked in the audio-recordings of the psychotherapy sessions and automatic speaker diarisation was used to determine the speaker-switching patterns in which the pauses occur. A random forest classifier detected time frames in which ruptures with the minimal response marker occurred based on the quantity of pauses. Performance was very good with an area under the ROC curve of 0.89. Pauses which were both preceded and followed by therapist speech were the most important predictors for minimal response ruptures. Research costs can be reduced by using machine learning techniques instead of manual rating for rupture detection. In combination with other video and audio derived features like movement analysis or automatic facial emotion detection, more complete rupture detection might be possible in the future. These innovative machine learning techniques help to narrow down the mechanisms of change of psychotherapy, here specifically of the therapeutic alliance. They might also be used to technologically augment psychotherapy training and supervision.

A surgical site infection (SSI) is one of the most common surgical complications. This study analyzed different sources of microorganisms in the air, on reusable surgical instruments, and the outer surface of sterile packaging systems during the use and reprocessing of sterile goods (from the operating room (OR) to the Central Sterile Supply Department (CSSD)). The microbial load in the air was analyzed via active air sampling and settle plates. Furthermore, the airborne particle load was measured by a particle counter. Contact agar plates were used to determine the microbial load on surgical instruments and sterile packaging systems. The highest average microbial and particle load was measured in the air of the OR (active air sampling: max. 56 CFU/m3; settle plates: max. 9 CFU; ≥0.3 μm particles in size: 1,958,403 no./m3). However, no microbial load (0 CFU) was detected on surgical instruments sampled in the OR. The outer surface of stored sterile packaging systems showed a maximal microbial load of 64 CFU. The most common identified pathogen was coagulase-negative staphylococci. Compared to properly reprocessed reusable surgical instruments and sterile packaging systems, the air still seems to be the primary potential source of microbial contamination, especially within the OR.

Computational prediction of absolute essential genes using machine learning has gained wide attention in recent years. However, essential genes are mostly conditional and not absolute. Experimental techniques provide a reliable approach of identifying conditionally essential genes; however, experimental methods are laborious, time and resource consuming, hence computational techniques have been used to complement the experimental methods. Computational techniques such as supervised machine learning, or flux balance analysis are grossly limited due to the unavailability of required data for training the model or simulating the conditions for gene essentiality. This study developed a heuristic-enabled active machine learning method based on a light gradient boosting model to predict essential immune response and embryonic developmental genes in Drosophila melanogaster. We proposed a new sampling selection technique and introduced a heuristic function which replaces the human component in traditional active learning models. The heuristic function dynamically selects the unlabelled samples to improve the performance of the classifier in the next iteration. Testing the proposed model with four benchmark datasets, the proposed model showed superior performance when compared to traditional active learning models (random sampling and uncertainty sampling). Applying the model to identify conditionally essential genes, four novel essential immune response genes and a list of 48 novel genes that are essential in embryonic developmental condition were identified. We performed functional enrichment analysis of the predicted genes to elucidate their biological processes and the result evidence our predictions. Immune response and embryonic development related processes were significantly enriched in the essential immune response and embryonic developmental genes, respectively. Finally, we propose the predicted essential genes for future experimental studies and use of the developed tool accessible at http://heal.covenantuniversity.edu.ng for conditional essentiality predictions.