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Interface recombination is one of the factors limiting the performance of Cu(In,Ga)Se_2 (CIGS). Especially in the absence of band grading at the front and rear surface, interface passivation approaches become important to improve device performance. The integration of an oxide layer as passivation layer at the front surface of the CIGS requires meticulous considerations in order not to impact the further steps of the solar cell production. In this article, a novel approach is reported to try to tackle the problem of interface recombination at the front surface of CIGS without affecting further solar cell production steps. In this approach, an Al_2O_3/HfO_2 multi-stack layer with contact openings is applied. NaCl template patterning with preliminarily selected parameters was used to create a homogeneous pattern of contact opening on the CIGS surface and allow the current flow in the device. After the removal of the NaCl islands, the holes in the multi-stack (openings) were visualized by scanning electron microscopy. In addition, energy-dispersive X-ray spectroscopy (EDS) was performed before and after chemical bath deposition of the buffer layer. The EDS result confirmed that the undesired etching of the Al_2O_3 layer during buffer layer deposition was prevented by using a thin HfO_2 layer. Solar cells were produced by using preliminarily selected parameters for the multi-stack design. As a result, without having a significant negative impact on the solar cell parameters, a device design was achieved which is almost comparable with the reference device. In addition, options for future improvement and development are discussed. European Union's H2020 Research and Innovation Program [715027]

In twin pregnancies, amnionicity and chorionicity are crucial as they strongly determine prenatal and perinatal management. First trimester ultrasound allows a highly reliable diagnosis of amnionicity and chorionicity, making it an internationally accepted standard in antenatal care. However, in rare cases, amnionicity can change from diamniotic to monoamniotic throughout pregnancy, substantially impacting perinatal management. We report the case of a confirmed monochorionic diamniotic twin pregnancy with a diagnosis of spontaneous septostomy of the dividing membrane (SSDM) at 28 weeks of gestation, resulting in a pseudomonoamniotic pregnancy. Even though SSDM is a rare condition and its sonographic diagnosis might be challenging, it should be considered if, in a known diamniotic pregnancy, there is a sudden failure to visualise the intertwin membrane truly separating both twins.

Background: Tractography based on diffusion-weighted magnetic resonance imaging (DWI) models the structural connectivity of the human brain. Deep brain stimulation (DBS) targeting the subthalamic n...

Private rental markets have become increasingly important since the Global Financial Crisis 2008–2009 and rent controls are back on the political agenda. Yet, they have received less attention from housing scholars than homeownership and public housing. This paper presents new data on the development of private tenancy legislation based on a content-coding of rent control, protection of tenants from eviction, and rental housing rationing laws across more than 15 countries and 100 years. This long-run perspective allows for inquiring about the dynamic effects of rent control on the rise of homeownership as the dominant tenure during the twentieth century. We find that both rent regulation and rationing measures were followed by increases of homeownership and decreases of private rentals. We suggest that homeownership was not just produced by generous subsidies or the homeownership dream, but also through the push-effect of regulation crowding out rental units. 1. Introduction 2. Literature on rent regulation and homeownership determinants 3. Data: tenancy regulation in the long-run 4. Estimation results 5. Discussion and conclusion Acknowledgements Disclosure statement Footnotes References Appendixes

Background Care homes were hit hard by the COVID-19 pandemic. Although high levels of psychosocial burden (i.e., anxiety, depression and stress) during the pandemic have been described for healthcare workers in hospitals, evidence on the psychosocial burden for nurses in care homes during the pandemic is scarce. Methods A total of 811 nurses participated in a retrospective online survey between November 2020 and February 2021. Information about the COVID-19 situation (i.e., working demands, COVID-19 cases in their facility, and COVID-19-related burden) of nurses in German care homes during the first wave of the pandemic (March 2020 to June 2020) was gathered. The Stress Scale of the Depression Anxiety and Stress Scales (SDASS-21), the Generalized Anxiety Disorder Scale-2 (GAD-2), the Patients-Health-Questionnaire-2 (PHQ-2), and the Copenhagen Psychosocial Questionnaire (COPSOQ) were used to screen for psychosocial burden. Results Among nurses, 94.2% stated that working demands since the COVID-19 pandemic increased. Further, 59.1% showed clinically relevant levels of either stress, anxiety, and/or depression. Multiple regression analysis showed significant associations between COVID-19-related burden and qualification (p < .01), dissatisfaction with COVID-19 management of care home manager (p < .05), COVID-19-related anxiety (p < .001), and dementia as a focus of care (p < .05). Stress, depression, and anxiety showed associations with COVID-19 related burden at work (p < .01), COVID-19-related anxiety (p < .001), social support (p < .01), and sense of community (p < .05). Stress was also associated with COVID-19 cases among residents (p < .05), and size of care home (p < .05). Conclusion Short- and long-term strategies (i.e., psychosocial counseling, mandatory team meetings, more highly qualified nurses, additional training) in the work environment of nursing, in crises, but beyond, should be encouraged to reduce the burden on nursing staff in care homes.

Periods of absence from supervised group exercise while maintaining physical activity might be a frequent pattern in adults' exercise habits. The aim of the present study was to determine detraining effects on musculoskeletal outcomes after a 3-month detraining period in early post-menopausal, osteopenic women. Due to the COVID-19 pandemic, we terminated the 18-month randomized controlled ACTLIFE exercise intervention immediately after the 13-month follow-up assessment. This put an abrupt stop to the high-intensity aerobic and resistance group exercise sessions undertaken three times per week by the exercise group (EG: n = 27) and the gentle exercise program performed once per week for the attention control group (CG: n = 27); but both groups were permitted to conduct individual outdoor activity for the 3-month lock-down period. Study endpoints were lean body mass (LBM), bone mineral density (BMD) at the lumbar spine (LS), maximum hip-/leg extension strength and power. Detraining-induced reductions of LBM, hip/leg strength and power (but not BMD-LS) were significantly greater (p p = 0.044) compared with the CG. Significant exercise effects, i.e. differences between EG and CG, present after 13 months of exercise, were lost after 3 months of detraining for LBM (p = 0.157) and BMD-LS (p = 0.065), but not for strength (p p Trial registration number: ClinicalTrials.gov: NCT04420806, 06.05.2020.

Purpose: The menopausal transition is a critical period in wo-men’s lives. The central aim of the present study was to evaluate the effect of a multimodal exercise protocol on the cardiometa-bolic risk factor potentially related to menopausal transition in early postmenopausal women. Methods: Fifty-four (54) early-postmenopausal women (54.0±1.8 years) were randomly assigned to two groups: (1) exercise group (EG: n=27) which conducted a high intensity aerobic and resistance training three times/week and (2) active control group (CG: n=27) exercising once a week with low exercise inten-sity. Besides bone density, the main variable of this project, the outcome variable in this thesis was also cardiometabolic risk, as summarized by the Metabolic Syndrome (MetS) Z-Score. We applied Intention-to-Treat (ITT) and Per Protocol Analyses (PPA) with multiple imputation and used standardized mean differences to illustrate the effects. Results: After 16 weeks of exercise two participants (EG: n=1; CG: n=1) were lost to follow-up. Effects for the MetS Z-Score were moderate (EG:-0.36±1.36 vs. CG: 0.51±2.28; SMD: 0.47, 95% CI:-0.08 to 1.03), albeit borderline non-significant (ITT: p=.089; PPA: p=.060). Conclusion: The present multimodal exercise protocol just fai-led to affect the MetS Z-Score and its underlying cardiometabolic risk factors. Whether this result can be generalized to the entire cohort of early-postmenopausal women or whether it has to be attributed to the only moderately high exercise intensity during the early weeks of the intervention along with a relatively short intervention period remains to be evaluated.

Purpose The absence of routine health check-ups during adolescence in low- and middle-income countries is a missed opportunity for prevention, early identification, and treatment of health issues, and health promotion. We aimed to codesign the content and delivery for routine adolescent health checkups in Zimbabwe, with adolescents and key adults in their lives. Methods We held participatory workshops with adolescents (16 workshops; 96 adolescents) and parents (8 workshops; 95 parents), and in-depth interviews with key informants including policymakers, programmers, and healthcare workers (n = 25). Analysis was iterative and the design of the checkups was refined based on participant preferences, document review of burden of disease data, and feasibility considerations. Results Participants overwhelmingly supported the introduction of routine health checkups. Reported facilitators to attendance included free cost and desire to know one’s health status. Barriers included tendencies for health service seeking only when ill, fear of diagnosis and judgment, and religious beliefs. Delivery preferences were by nonjudgmental medical professionals, in a youth friendly environment, and accompanied by youth engagement activities. Preferred location was schools for younger adolescents (10–14 years), and community settings for older adolescents (15–19 years). Prioritized content included sexual health, oral health, mental health, hearing, eyesight, growth and nutrition, anemia, immunization, and deworming, based on health burden and participant preferences. Discussion This study resulted in an outline design of two routine health checkups with stakeholders in Zimbabwe, in schools for young adolescents, and in community settings for older adolescents. Evidence of feasibility, effectiveness, and cost-effectiveness of such checkups is required.

Background Currently, interpretation of prostate MRI is performed qualitatively. Quantitative assessment of the mean apparent diffusion coefficient (mADC) is promising to improve diagnostic accuracy while radiomic machine learning (RML) allows to probe complex parameter spaces to identify the most promising multi-parametric models. We have previously developed quantitative RML and ADC classifiers for prediction of clinically significant prostate cancer (sPC) from prostate MRI, however these have not been combined with radiologist PI-RADS assessment. Purpose To propose and evaluate diagnostic algorithms combining quantitative ADC or RML and qualitative PI-RADS assessment for prediction of sPC. Methods and population The previously published quantitative models (RML and mADC) were utilized to construct four algorithms: 1) Down(ADC) and 2) Down(RML): clinically detected PI-RADS positive prostate lesions (defined as either PI-RADS≥3 or ≥4) were downgraded to MRI negative upon negative quantitative assessment; and 3) Up(ADC) and 4) Up(RML): MRI-negative lesions were upgraded to MRI-positive upon positive assessment of quantitative parameters. Analyses were performed at the individual lesion level and the patient level in 133 consecutive patients with suspicion for clinically significant prostate cancer (sPC, International Society of Urological Pathology (ISUP) grade group≥2), the test set subcohort of a previously published patient population. McNemar test was used to compare differences in sensitivity, specificity and accuracy. Differences between lesions of different prostate zones were assessed using ANOVA. Reduction in false positive assessments was assessed as ratios. Results Compared to clinical assessment at the PI-RADS≥4 cut-off alone, algorithms Down(ADC/RML) improved specificity from 43% to 65% (p = 0.001)/62% (p = 0.003), while sensitivity did not change significantly at 89% compared to 87% (p = 1.0)/89% (unchanged) on the patient level. Reduction of false positive lesions was 50% [26/52] in the PZ and 53% [15/28] in the TZ. Algorithms Up(ADC/RML) led, on a patient basis, to an unfavorable loss of specificity from 43% to 30% (p = 0.039)/32% (p = 0.106), with insignificant increase of sensitivity from 89% to 96%/96% (both p = 1.0). Compared to clinical assessment at the PI-RADS≥3 cut-off alone, similar results were observed for Down(ADC) with significantly increased specificity from 2% to 23% (p 0.001) and unchanged sensitivity on the lesion level; patient level specificity increased only non-significantly. Conclusion Downgrading PI-RADS≥3 and ≥ 4 lesions based on quantitative mADC measurements or RML classifiers can increase diagnostic accuracy by enhancing specificity and preserving sensitivity for detection of sPC and reduce false positives.

Highlights • KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. • Disease course can be unpredictable and may severely affect children and young adults. • Findings suggest a potential window for intervention until 40 years of age, albeit with variability between patients due to macular atrophy., Purpose To describe the detailed retinal phenotype of KCNV2-associated retinopathy. Study design Multicenter international retrospective case series. Methods Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. Results Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes. Conclusions KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.

Background There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. Objectives In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. Methods We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. Results Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. Conclusion Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

Background: Bornholm eye disease (BED) is a rare X-linked cone dysfunction disorder with high myopia, amblyopia, and color vision defects.Materials and methods: Visual and ocular outcomes in a family where two of five siblings had molecularly confirmed BED are reported. Ophthalmological assessments included best-corrected visual acuity (BCVA), color vision test, and optical coherence tomography (OCT). Medical records, electroretinography (ERG), and genetic analyses were re-evaluated.Results: Two male siblings had confirmed BED with myopia and protanopia. The younger brother had high myopia, subnormal BCVA, and ocular fundi that showed tilted discs, crescent shaped peripapillary atrophy, and visible choroidal vessels. OCT confirmed retinal and choroidal atrophy. The older brother was lightly myopic with normal/subnormal BCVA and subtle findings in the fundi. Both brothers had abnormal ERG recordings with a decreased cone response. They also had a structurally intact OPN1LW/OPN1MW gene cluster. The OPN1LW gene was shown to carry a deleterious variant combination in exon 3 known to result in mis-splicing of opsin mRNA and acknowledged as LIAVA amino acid delineation (Leu153-Ile171-Ala174-Val178-Ala180), while the OPN1MW gene exon 3 showed a non-pathogenic variant combination (MVVVA). Another normal-sighted brother carried another wildtype variant combination (LVAIS) in exon 3 of the OPN1LW gene.Conclusions: The two affected brothers demonstrated a large variability in their phenotypes even though the genotypes were identical. They presented a disease-associated haplotype in exon 3 of OPN1LW that has been described as the molecular cause of BED.

Objectives. To examine the effects of warm footbaths with thermogenic medicinal powders on vitality and heart rate variability in healthy adults. Intervention and Outcome. Seventeen healthy young adults (22.1 ± 2.4 years, 11 females) received three footbaths (WA: warm water only; GI: warm water and ginger; MU: warm water and mustard) in randomized order with a crossover design. We assessed vitality with the Basler Befindlichkeit questionnaire (BBS) and heart rate variability (HRV) before (t0), immediately after (t1), and 10 minutes following footbaths (t2). The primary outcome measure was self-reported vitality, measured via the BBS, at t1. Results. The primary outcome measure, self-reported vitality, was higher after GI and tended to be higher after MU compared to WA with medium effect sizes (GI vs. WA, mean difference −2.47 (95% CI −5.28 to 0.34),padj=0.048, dadj = 0.74), MU vs. WA, −2.35 (−5.32 to 0.61),padj=0.30, dadj = 0.50). At t2, the standard deviation of beat-to-beat intervals (SDNN) of HRV increased, and the stress index tended to decrease after all three footbath conditions with small to medium effect sizes (0.42–0.66). Conclusion. There is preliminary evidence that footbaths with thermogenic agents GI and MU may increase self-reported vitality during a short-time period with a more pronounced effect with GI. After a short follow-up, all three conditions tended to shift the autonomic balance towards relaxation. Future research should investigate these effects in clinical samples with a larger, more diverse sample size.

Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure1. Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold2, at a scale that covers almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions that are likely to be disordered. Finally, we provide some case studies to illustrate how high-quality predictions could be used to generate biological hypotheses. We are making our predictions freely available to the community and anticipate that routine large-scale and high-accuracy structure prediction will become an important tool that will allow new questions to be addressed from a structural perspective., AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.

AimsTo determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).MethodsDetails of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.ResultsNo adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.ConclusionThe results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

ZusammenfassungWiederholt episodenhaft auftretende Atemnot ist im Kindes- und Jugendalter ein häufiges Symptom. Neben anstrengungsinduzierter Bronchialobstruktion im Rahmen eines Asthma bronchiale ist eine funktionelle Genese eine sehr häufige Differenzialdiagnose. Dennoch wird diese Diagnose häufig nicht oder mit langer Latenz gestellt. Unter dem Oberbegriff „ILO“ („inducible laryngeal obstruction“) werden sowohl funktionelle supraglottische Obstruktionen durch Kollaps der Knorpelstrukturen als auch Dysfunktionen auf Glottisebene wie „vocal cord dysfunction“ (VCD) subsumiert. Körperliche Anstrengung ist ein häufiger Auslöser; es werden jedoch auch Beschwerdebilder ohne Anstrengungsbezug beobachtet. Es wird der Erkenntnisstand zur Pathophysiologie referiert und die klinische Präsentation beschrieben. Ein wesentlicher Fokus des Artikels liegt im Folgenden auf der Darstellung eines sinnvollen und Ressourcen-orientierten diagnostischen Vorgehens. Der CLE-Test („continuous laryngoscopy exercise test“) als Provokationsmethode unter Wach-Videolaryngoskopie ist der Goldstandard, jedoch wird diese Diagnostik im deutschsprachigen Raum nicht flächendeckend vorgehalten. Dieses Positionspapier stellt daher die diagnostische Wertigkeit verschiedener anderer Diagnostik-Algorithmen und anamnestischer Informationen heraus. Ein weiterer Schwerpunkt des Papiers besteht in der detaillierten Vorstellung geeigneter atemphysiotherapeutischer Interventionen.

Currently, lactate (Lac) is used to evaluate machine perfusion (MP) of hearts, donated after circulatory death (DCD). We hypothesize that monitoring of myocardial microcirculation (mLDP) by Laser-Doppler-Perfusion is superior to Lac to evaluate perfusion and predict contractility. In a pig model, DCD-hearts were perfused 4 hours followed by reperfusion and left ventricular contractility measurement. Lac and mLDP were measured every 30 min in successfully (N = 9) and unsuccessfully (N = 7) maintained hearts. Successfully maintained hearts showed decreasing Lac (5.6 to 2.8 mmol/L) and slightly downregulated (92%) mLDP. In unsuccessfully maintained hearts Lac first decreased (5.1 to 3.8 mmol/L) followed by increase and mLDP dropped to 39%. In a single-variable regression only mLDP showed a significant r² for systolic (0.514, p = 0.045) and diastolic (0.501, p = 0.049) parameters. The combination of mLDP and Lac (r2 = 0.876, p = 0.005) showed best results. mLDP seems to be superior to Lac to show perfusion disorders and predict DCD-heart contractility.

Purpose To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. Study design This was a multicenter international clinical cohort study. Methods Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. Results In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. Conclusion In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics., Highlights • The current study established the largest and most characterized cohort of molecularly confirmed patients with KCNV2-associated retinopathy. • Report 1 highlights the genetic background, evidence of electroretinography stability over a broad age range, and the severe phenotype of the disease.

Introduction Disease-causing mutations in the protocadherin FAT1 have been recently described both in patients with a glomerulotubular nephropathy and in patients with a syndromic nephropathy. Methods We identified 4 patients with FAT1-associated disease, performed clinical and genetic characterization, and compared our findings to the previously published patients. Patient-derived primary urinary epithelial cells were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblotting to identify possible alterations in Hippo signaling. Results Here we expand the spectrum of FAT1-associated disease with the identification of novel FAT1 mutations in 4 patients from 3 families (homozygous truncating variants in 3, compound heterozygous missense variants in 1 patient). All patients show an ophthalmologic phenotype together with heterogeneous renal phenotypes ranging from normal renal function to early-onset end-stage kidney failure. Molecular analysis of primary urine-derived urinary renal epithelial cells revealed alterations in the Hippo signaling cascade with a decreased phosphorylation of both the core kinase MST and the downstream effector YAP. Consistently, we found a transcriptional upregulation of bona fide YAP target genes. Conclusion A comprehensive review of the here identified patients and those previously published indicates a highly diverse phenotype in patients with missense mutations but a more uniform and better recognizable phenotype in the patients with truncating mutations. Altered Hippo signaling and de-repressed YAP activity might be novel contributing factors to the pathomechanism in FAT1-associated renal disease., Graphical abstract

In this article, the design and characterization of package-embedded solenoid inductors for a high-efficiency, four-phase system-in-package (SIP) buck-type integrated voltage regulator (IVR) switching at 100 MHz is discussed. The IVR enables three conversion ratios (5, 3, and 1.7–1 V) with a minimum inductance of 25 nH/phase and a load current of 10 A (2.5 A/phase). Two inductor designs (one with a rectangular core made of an epoxy dielectric/NiZn ferrite composite magnetic material/epoxy dielectric stack and one with an elliptical core of NiZn ferrite composite magnetic material only) were optimized and compared based on the highest achievable IVR efficiency. At high-load conditions (>5 A), the elliptical core inductor showed higher efficiency than the rectangular core inductor over the frequency range investigated (10–100 MHz). The elliptical core inductors were fabricated using a novel fabrication process combining core printing, noncontact photolithography, and copper electroplating. Two simple deembedding techniques which use a single thru structure and its equivalent circuit model as well as a cascade-based two-port analysis were introduced for the characterizations of the fabricated inductors. The accuracy of these deemebedding techniques was assessed using commercial, fixed-air core inductors and standard THRU and thru–reflect–line (TRL) deembedding for comparison purpose. Less than 5% difference was observed between the TRL and the introduced deembedding techniques for the inductance and ac resistance for both the fixed air core and package-embedded magnetic core inductors. The extracted electrical parameters of the fabricated inductors were compared with the modeling results and a good correlation was observed at 100 MHz.

Background: In response to conflicting findings for activity levels across sociodemographic groups, this study examined differences in adolescents’ in-school, out-of-school, and weekend physical activity (PA) by sociodemographic subgroups using representative US data. Methods: Data were obtained from the Family Life, Activity, Sun, Health, and Eating study. Multiple regression models compared in-school, out-of-school, and weekend PA by gender and race/ethnicity, and examined potential modification of associations by grade (middle vs high school) and socioeconomic status (lower vs higher). Results: Final analytic sample was 1413 adolescents (Mean age = 14.5 y, 51.3% female, 64.5% white). Compared with whites, in-school PA was significantly higher among blacks and those classified as other race/ethnicity for middle school (69.8 and 71.0, respectively, vs 66.4 min/d), and among Hispanics for high school (52.7 vs 48.4 min/d). Hispanics’ (vs whites’) out-of-school PA was significantly lower for middle school (63.7 vs 66.6 min/d), but higher for high school (54.0 vs 51.8 min/d). In-school PA was significantly higher among adolescents of lower (vs higher) socioeconomic status among males and Hispanics (all Ps Conclusions: The relation of race/ethnicity with PA varies by grade and time of day/week. Socioeconomic status findings contradict previously reported findings. Efforts to increase PA based on sociodemographic disparities should consider potential interaction effects.

Item does not contain fulltext BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

Background The purpose of this study was to: 1) examine the maintenance of Physical Education and physical activity during the distance learning time, 2) determine the resources educators are utilizing to deliver PE curricula, and 3) understand the challenges experienced by educators during distance learning. Methods A survey was sent to a cohort of school-based fitness assessment software users. Respondents were largely school-based individuals including PE teachers (n = 1789), school (n = 62) and district administrators (n = 64), nurses (n = 3), and “other” (n = 522). Results Of 2440 respondents, most were from a city or suburb (69.7%), elementary or middle school (72.3%), and had Title 1 status (60.4%), an indicator of low socioeconomic status. Most campuses were closed during the COVID-19 pandemic (97.8%). Of the schools closed during the pandemic, only 2.8% had no prior PE requirements and that increased to 21% during the pandemic. In schools that remained open during the pandemic, 7.7% had no prior PE requirements and this increased to 60.5%. Importantly, 79% of respondents reported that students were either “significantly less” or “somewhat less” physically active during the closure. For closed schools, the most frequently cited challenges included “student access to online learning“, “teacher/student communication” and “teacher remote work arrangements”. For open schools, the most commonly reported challenges included “social distancing”, “access to gymnasium/equipment”, and “concern for personal health and wellbeing”. Conclusion The COVID-19 pandemic has caused important reductions in PE requirements and time engaged in physical activity. Challenges experienced by teachers were identified for closed and open schools.

A 39-year-old man presented with chest pain initially attributed to viral pericarditis. He was found to have an embolized inferior vena cava filter strut that perforated the right ventricle. Inferior vena cava filter fracture and embolization should be considered in patients with chest pain and pericardial effusion. (Level of Difficulty: Beginner.), Graphical abstract

Endoskopische Diagnostik und Interventionen bei Kindern erfordern ein hohes Mas an Expertise aus unterschiedlichen Bereichen. Die kleinen Dimensionen, die Vulnerabilitat der Patienten*innen und die Seltenheit der Erkrankungen und Problematiken einerseits und die Notwendigkeit modernster Endoskopietechnik andererseits konnen nur durch ein adaquat aufgestelltes Team gemeistert werden. Wir beschreiben typische Indikationen, personelle und technische Anforderungen und machen Vorschlage zur Prozessorganisation. Die Notwendigkeit zum interdisziplinaren Vorgehen wird an 3 exemplarischen Beispielen geschildert. Kein Fachgebiet allein kann die vielfaltigen Herausforderungen der Kinderendoskopie alleine bewaltigen. Die Organisation sollte deshalb niederschwellige Kooperationen begunstigen. Vor allem im Bereich der Fruhgeborenenversorgung und Kindern mit Darmversagen und Motilitatsstorungen bedarf es weiterer Technikentwicklungen.

Position paper of the Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition. In 2019 the German Federal Institute for Drugs and Medical Devices (Bundesinstitut fur Arzneimittel und Medizinprodukte, BfArM) launched a “doctors letter” (Rote-Hand-Brief) recommending light protection of all parenteral nutrition (PN) solutions during administration for preterm infants, term infants and children less than 2 years of age. The aim of the present paper is to review the available evidence and provide evidence-based recommendations for hospital and home PN light protection in children. The Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition recommend in accordance with the recommendations of the ESPGHAN, ESPEN, ESPR and CESPEN guidelines on pediatric parenteral nutrition: 1. Lipid emulsions and/or vitamins containing PN solutions should be protected from light during administration (bags and tubing) to prevent the generation of oxidants. 2. There is no conclusive evidence for recommending light protection for PN solutions without lipid emulsions and without vitamins during administration (solutions containing, e.g. amino acids, glucose, electrolytes, or trace elements). In addition, in home PN non-light-protected spiral tubing may be used because validated light-protected spiral tubing is currently not available, given that spiral tubing improves the range of motion and safety in infants and young children.

BackgroundVoretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue.MethodsSeven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months.ResultsAll except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R2>0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R2=0.5).ConclusionsThe presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.

Osteosarcopenia is characterized by a progressive decline in muscle function and bone strength and associated with muscle fat accumulation. This study aimed to determine the effect of long-term high intensity resistance training (HIRT) on thigh muscle fat infiltration in older men with osteosarcopenia. Forty-three community-dwelling men (72 years and older) were randomly assigned to either an exercise group (EG, n = 21) or an inactive control group (CG, n = 22). EG participants performed a supervised single-set exercise training with high effort two times per week. Participants of both groups were individually provided with dietary protein to reach a cumulative intake of 1.5-1.6 g/kg/day or 1.2-1.3 g/kg/day (EG/CG), respectively, and Up to 10,000 IE/week of Vitamin-D were supplemented in participants with 25 OH Vitamin-D 3 levels below 100 nmol/l. Magnetic resonance (MR) imaging was performed to determine muscle and adipose tissue volume and fat fraction of the thigh. At baseline, there were no significant differences between the two groups. After 16 month,, there were significant training effects of 15% (p = 0.004) on intermuscular adipose tissue (IMAT) volume, which increased in the CG (p = 0.012) and was stable in the EG. In parallel, fat fraction within the deep fascia of the thigh (Baseline, EG: 18.2 vs CG: 15.5, p = 0.16) significantly differed between the groups (Changes, EG: 0.77% vs. CG: 7.7%, p = 0.009). The study confirms the role of fat infiltration of the muscles as an advanced imaging marker in osteosarcopenia and the favorable effects of HIRT on adipose tissue volume of the thigh, in men with osteosarcopenia.

The success of data-driven maintenance is strongly dependant on effective use of AI and multi-structured data sources. Introducing and integrating an AI-enhanced methodology in reliability-centred maintenance study of complex production systems leads to reducing failure rates and optimizing availability. In manufacturing enterprises, information about machine failures and expert knowledge are often stored in digital shift books (DSB). This paper introduces a transferable and scalable AI-enhanced methodology for DSB in automotive industry, which enhances Overall Equipment Efficiency (OEE) by optimizing availability through reducing the Mean Failure Detection Time (MFDT). Experimental investigations in the use-case suggest an OEE increase by over 5%.

Aims Patients with tetralogy of Fallot (TOF) are often affected by right ventricular fibrosis, which has been associated with arrhythmias. This study aimed to assess fibrosis distribution in right ventricular outflow tract (RVOT) myocardium of TOF patients to evaluate the utility of single histology-section analyses, and to explore the possibility of fibrosis quantification in unlabelled tissue by second harmonic generation imaging (SHGI) as an alternative to conventional histology-based assays. Methods and results We quantified fibrosis in 11 TOF RVOT samples, using a tailor-made automated image analysis method on Picrosirius red-stained sections. In a subset of samples, histology- and SHGI-based fibrosis quantification approaches were compared. Fibrosis distribution was highly heterogeneous, with significant and comparable variability between and within samples. We found that, on average, 67.8 mm2 of 10 µm thick, histologically processed tissue per patient had to be analysed for accurate fibrosis quantification. SHGI provided data faster and on live tissue, additionally enabling quantification of collagen anisotropy. Conclusion Given the high intra-individual heterogeneity, fibrosis quantification should not be conducted on single sections of TOF RVOT myectomies. We provide an analysis algorithm for fibrosis quantification in histological images, which enables the required extended volume analyses in these patients.

Background: Coronavirus disease 2019 (COVID-19) mortality has waned significantly over time; however, factors contributing towards this reduction largely remain unidentified. The purpose of this study was to evaluate the trend in mortality at our large tertiary academic health system and factors contributing to this trend. Methods: This is a retrospective cohort study of intensive care unit (ICU) patients diagnosed with COVID-19 between March and August 2020 admitted across 14 hospitals in the Philadelphia area. Collected data included demographics, comorbidities, admission risk of mortality score, laboratory values, medical interventions, survival outcomes, hospital and ICU length of stay (LOS) and discharge disposition. Chi-square (? 2 ) test, Fisher exact test, Cochran-Mantel-Haenszel method, multinomial logistic regression models, independent sample t -test, Mann-Whitney U test and one-way analysis of variance (ANOVA) were used. Results: A total of 1,204 patients were included. Overall mortality was 39%. Mortality declined significantly from 46% in March to 14% in August 2020 (P < 0.05). The most common underlying comorbidities were hypertension (60.2%), diabetes mellitus (44.7%), dyslipidemia (31.6%) and congestive heart failure (14.7%). Hydroxychloroquine (HCQ) use was more commonly associated with the patients who died, while the use of remdesivir, tocilizumab, steroids and duration of these medications were not significantly different. Peak values of ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer levels were significantly higher in patients who died (P < 0.05). The mean hospital LOS was significantly longer in the patients who survived compared to the patients who died (18 vs. 12, P < 0.05). Conclusions: The mortality of patients admitted to our ICU system significantly decreased over time. Factors that may have contributed to this may be the result of a better understanding of COVID-19 pathophysiology and treatments. Further research is needed to elucidate the factors contributing to a reduction in the mortality rate for this patient population. J Clin Med Res. 2021;13(3):184-190 doi: https://doi.org/10.14740/jocmr4452

Delegates from the 35 member countries of the European Association of Hospital Pharmacists (EAHP) came together on 11 and 12 June for the 51st General Assembly. Because of the COVID-19 pandemic this gathering was virtual. During the General Assembly, delegates received updates on EAHP’s educational activities, the core projects of the Association and current policy developments. Discussions centred on the implementation of the 44 European Statements of Hospital Pharmacy, the Common Training Framework for hospital pharmacy specialisation, access to medicines and the growing problem of medicines shortages, in particular those linked to immunoglobulins that are increasingly impacting patient care. At the end of the General Assembly, Andras Sule was welcomed as EAHP’s new President. For the next 3 years, he will be steering the Association. Dr Andras Sule is currently the Chief Pharmacist at Peterfy Hospital and Trauma Centre as well as the Chief Pharmacy Advisor at Duna Medical Centre, both located in Hungary. He is a guest lecturer and lead developer of the Hospital Pharmacy Specialisation programme at Semmelweis University in Budapest. In 2008, he obtained a PhD from Semmelweis University and has since gone on to complete a PharmD Specialisation in Pharmaceutical Technology and a PharmD Specialisation in Clinical Pharmacy. Reflecting on the goals for this 3 year presidency, Dr Andras Sule outlined the following: “I feel very honoured to take over EAHP’s primary leadership role from Petr Horak and his predecessors who have done a great job in improving patient care and advancing the hospital pharmacy profession in the almost 50 years that our Association now exists. I will have some very big shoes to fill, especially since I am taking over as EAHP’s President during a global pandemic. However, knowing our profession has gone above and beyond during this unprecedented time, I also feel confident that …

Biomedical imaging is a driver of scientific discovery and a core component of medical care and is being stimulated by the field of deep learning. While semantic segmentation algorithms enable image analysis and quantification in many applications, the design of respective specialized solutions is non-trivial and highly dependent on dataset properties and hardware conditions. We developed nnU-Net, a deep learning-based segmentation method that automatically configures itself, including preprocessing, network architecture, training and post-processing for any new task. The key design choices in this process are modeled as a set of fixed parameters, interdependent rules and empirical decisions. Without manual intervention, nnU-Net surpasses most existing approaches, including highly specialized solutions on 23 public datasets used in international biomedical segmentation competitions. We make nnU-Net publicly available as an out-of-the-box tool, rendering state-of-the-art segmentation accessible to a broad audience by requiring neither expert knowledge nor computing resources beyond standard network training.

ZusammenfassungDie Adenomyose ist durch endometriale Zellen im Myometrium charakterisiert. Zu den klinischen Beschwerden gehören Schmerzen, Blutungsstörungen und beeinträchtigte Fertilität. Die Abklärung beinhaltet eine gute Anamnese und die Bildgebung mit transvaginalem Ultraschall (TVUS) sowie ggf. Magnetresonanztomographie. Klassisch zeigt sich die Adenomyose im TVUS durch partielle Aufhebung der Junktionalzone. Die Therapie erfolgt ganzheitlich und beinhaltet ein gutes Schmerzmanagement. Bei jungen Patientinnen sollte eine endokrine Therapie erfolgen. Die Kinderwunschtherapie kann mit einer 3‑monatigen Down-Regulation mit Gonadotropin-Releasing-Hormon(GnRH)-Analoga eingeleitet werden. Bei notwendiger In-vitro-Fertilisation haben Protokolle mit ultralanger Down-Regulation oder zeitlich versetztem Embryotransfer nach GnRH-Analoga bessere Resultate gezeigt. Bei fortgeschrittener Erkrankung, abgeschlossener Familienplanung oder Therapieresistenz kommt die operative Sanierung oder Hysterektomie infrage.

The 2030 Agenda for Sustainable Development promotes with the Sustainable Development Goal 4 a quality education for all and aims to ensure equal access to all levels of education and vocational training for vulnerable groups, such as Indigenous Peoples. However, most education systems are not yet in a position to embrace a culturally appropriate way of teaching children and youth of their Indigenous communities. The #IndigenousESD research creates a voice for relevant education stakeholder groups, including Indigenous Elders/leaders, ministry officials, parents, students, and teachers from communities with Indigenous students on their perceptions of quality education. Based on a participatory research approach developed together with Indigenous communities and researchers from around the world, dialogues held in 54 research settings in 26 countries show a focus on the acquisition of twenty-first century competencies for learners amongst the most important aspects of a quality education. For this article, the authors focused on knowledge, attitudes and skills, providing recommendations for policy makers in education to better address the needs and priorities of Indigenous communities. Findings from the research indicate that teaching twenty-first century competencies are at the center of concern in all stakeholder groups, yet want these competencies taught in a context to which Indigenous students can readily relate. Adjusting the pedagogy of delivering these common competencies in the classroom could be an important step towards a feasible and affordable path within existing education systems to better serve Indigenous students and all learners.

AIM Breastfeeding has numerous advantages. Our aim was to investigate whether breastfeeding initiation and duration in women with pregnancies conceived through in vitro fertilisation differ from spontaneously conceived pregnancies. METHODS This is a comparative cross-sectional study about breastfeeding behaviour performed at the Bern University Hospital including mothers of singletons conceived by in vitro fertilisation (n = 198) with or without gonadotropin stimulation between 2010 and 2016 (in vitro fertilisation group). They were compared to a population-based control group (n = 1421) of a randomly selected sample of mothers in Switzerland who delivered in 2014. RESULTS A total of 1619 women were included in this analysis. Breastfeeding initiation rates were high, similar between the in vitro fertilisation group (93.4%) and the control group (94.8%). No increased risk of stopping breastfeeding earlier after in vitro fertilisation treatment compared to the control group could be found over the observational period of 12 months (HR = 1.00, 95% CI 0.83-1.20, P = .984). There was no difference in breastfeeding initiation or duration after gonadotropin-stimulated vs unstimulated in vitro fertilisation. CONCLUSION In Switzerland, in vitro fertilisation treatments were not associated with earlier breastfeeding cessation. This result is reassuring for mothers undergoing in vitro fertilisation.

Magnons, the quanta of spin waves, could be used to encode information in beyond-Moore computing applications, and magnonic device components, including logic gates, transistors, and units for non-Boolean computing, have already been developed. Magnonic directional couplers, which can function as circuit building blocks, have also been explored, but have been impractical because of their millimetre dimensions and multi-mode spectra. Here, we report a magnonic directional coupler based on yttrium iron garnet single-mode waveguides of 350 nm width. We use the amplitude of a spin-wave to encode information and to guide it to one of the two outputs of the coupler depending on the signal magnitude, frequency, and the applied magnetic field. Using micromagnetic simulations, we also propose an integrated magnonic half-adder that consists of two directional couplers and processes all information within the magnon domain with aJ energy consumption., 26 pages, 10 figures. arXiv admin note: text overlap with arXiv:1902.02855

Recent translational data suggest that deep brain stimulation (DBS) of the cortico-striato-thalamo-cortical (CSTC) loops improves sensorimotor gating in psychiatric disorders that show deficient prepulse inhibition (PPI), a robust operational measure of sensorimotor gating. To our knowledge we are the first to investigate this effect in patients with Tourette syndrome (TS). We measured PPI of the acoustic startle reflex in patients with TS (N = 10) or Obsessive-Compulsive Disorder (OCD) (N = 8) treated with DBS of the centromedian and ventro-oral internal thalamic nucleus and the anterior limb of internal capsule-nucleus accumbens area respectively, and aged- and gender-matched healthy controls (HC). PPI of the DBS groups was measured in randomized order in the ON and OFF stimulation condition. Statistical analysis revealed no significant difference in PPI (%) of patients with TS between ON (M = 20.5, SD = 14.9) and OFF (M = 25.2, SD = 29.7) condition. There were significantly reduced PPI levels in patients with TS in the ON condition compared to HC (M = 49.2, SD = 10.7), but no significant difference in PPI between TS in the OFF condition and HC. Furthermore, we found no significant stimulation or group effect for OCD and HC (OCD ON: M = 57.0, SD = 8.3; OCD OFF: 67.8, SD = 19.6; HC: M = 63.0, SD = 24.3). Our study has a number of limitations. Sample sizes are small due to the restricted patient collective. The study was not controlled for use of psychoactive medication or nicotine. Furthermore, we were not able to assess presurgical PPI measurements. In conclusion, we were able to show that PPI is impaired in patients with TS. This finding is in line with recent translational work. With respect to the OCD cohort we were not able to replicate our previously published data. A disability in sensorimotor gating plays a pivotal role in many psychiatric disorders therefore more research should be conducted to disentangle the potential and limitations of modulating sensorimotor gating via brain stimulation techniques.

The article presents a comparative analysis of maturity level in Industry 4.0, of Brazilian companies with German Industry, seeking to identify learning opportunities to increase competitiveness. It was used the maturity model in Industry 4.0 developed by VDMA (German Mechanical Engineering Industry Association), applied to German companies, serving as benchmark. The same model was applied to Brazilian companies, from the State of Espírito Santo, located in the most developed region of the country, but with lower industrial density, and which has great challenges to increase its participation in the national and international markets. A field research was carried out with 46 industries, which participated in workshops to understand the fundamentals and to evaluate the maturity level in Industry 4.0. The individual results were processed by the platform of VDMA, indicating the levels in six dimensions of the model and the general result on a scale of 0 to 5. The results of all companies were tabulated, allowing the comparison with the research carried out with German companies. The study showed that, on average, Brazilian companies have the same level of maturity of German companies in readiness for Industry 4.0, with grade 0.9 in a scale of 0 to 5. But, there are significant differences in compared dimensions. 5.6% of German companies are at the advanced level in Industry 4.0, especially the technology developers, while Brazilian companies studied are still at the most basic levels. Both Industries are skeptical about investments in Industry 4.0 and the level of evaluation on Strategy dimension is still low. The comparison of expectations and difficulties allowed identify essential points to support these companies to follow the way to Industry 4.0.

Objective: \ud \ud This review will systematically examine and synthesize the evidence evaluating the effectiveness and safety of interventions that enable non-allergy specialist health care workers to assess allergy risk in patients with reported penicillin allergies and subsequently remove erroneous allergy records.\ud \ud \ud \ud Introduction: \ud \ud The potential benefits of removing erroneous penicillin allergy labels (de-labeling) are wide-ranging. Penicillin allergy assessment and de-labeling is an antibiotic stewardship priority. Delivery of such assessment and de-labeling by non-allergy specialists has been reported in several studies, but the effectiveness and safety have not been formally synthesized. This is a necessary step in the upscaling of penicillin allergy assessment services.\ud \ud \ud \ud Inclusion criteria: \ud \ud This review will consider quantitative studies using appropriate designs. The studies will include adults and pediatric patients who have undergone penicillin allergy assessment and de-labeling by non-allergy specialists in any health care setting.\ud \ud \ud \ud Methods: \ud \ud A range of databases will be searched to identify studies published in English, with no date limit. Unpublished studies and gray literature will also be searched. Title and abstract screening, and assessment of selected full texts against the inclusion criteria will be conducted by at least two independent reviewers. Identified studies will be assessed for methodological quality using standardized critical appraisal instruments. Data will be extracted and categorized using the EPOC taxonomy, and the effectiveness and safety of the intervention will be determined. Where possible, data will be pooled to facilitate meta-analysis. Data from heterogeneous studies will be reported narratively. The GRADE approach for grading the certainty of evidence will be followed.\ud \ud \ud \ud Systematic review registration number: \ud \ud PROSPERO CRD42020219044

Contains fulltext : 241592.pdf (Publisher’s version ) (Open Access) Objectives: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers. Materials and Methods: Fifteen patients (six male) with otherwise treatment-refractory OCD receiving ALIC/NAc DBS performed a flanker task with EEG recordings at three sessions: presurgery, and at follow-up with DBS on and off. We examined MFT, ERN, and task performance. Furthermore, we investigated interrelations with clinical efficacy and the explored the influence of the location of individual stimulation volumes on EEG modulations. Results: MFT and ERN were significantly attenuated by DBS with differences most pronounced between presurgery and DBS-on states. Also, we observed reaction time slowing for erroneous responses during DBS-off. Larger presurgery ERN amplitudes were associated with decreased clinical efficacy. Exploratory anatomical analyses suggested that stimulation volumes encompassing the NAc were associated with MFT modulation, whereas ALIC stimulation was associated with modulation of the ERN and clinical efficacy. Conclusion: ALIC/NAc DBS diminished MFT and ERN, demonstrating modulation of the medial frontal performance monitoring system in OCD. Furthermore, our findings encourage further studies to explore the ERN as a potential predictor for clinical efficacy. 8 p.

Purpose Higher education and its leadership are not yet using their potential impact for a sustainable future. This paper aims to focus on UN developments and the long history of university involvement in sustainability might create more interest and understanding that sustainably oriented universities are actually possible and a much stronger role for higher education is needed when nations are discussing their future. Design/methodology/approach Literature review with a focus on international treaties and declarations on the UN level and international university networks, literature review of the background and potential of the whole-institution approach and the need/suggestions for further research, also to measure advancement. Findings History shows a strong engagement of higher education with sustainability from its beginnings. There have been strong calls/offers from within university networks to take a crucial role in moving towards sustainable development that involves more than teaching about sustainability. The international community calls for higher education to be involved in policymaking rather than simply implementation, have been limited and the full potential of higher education institutions using all opportunities such as being living labs for sustainability has not as yet been realized. Currently, calls for engagement are often still limited to training and providing research when scientific evidence is wanted. Research limitations/implications Literature review focused on UN level treaties/declarations English- and German-language review national developments limited to samples of members of the Sustainable Development Goal (SDG) 4 subcluster in the Higher Education and Research for Sustainable Development (HESD) Global Cluster by the International Association of Universities (IAU). Practical implications Guidance for university leaders and other stakeholders to become aware of and consider a whole-institution approach. Practitioner relevance as countries is encouraged to embed UN recommendations, treaties and declarations. Defining opportunities for further research. Presenting the HESD Cluster by the IAU as a sample for new approaches of higher education to interact with the SDGs. Social implications Strengthening the role of higher education in the pursuit of a better future would focus on science and research as a neutral basis for decision-making and policy development. Sustainability embedded in all streams of university can help universities to be a practical example of the possibilities of sustainability at work. Originality/value Composition of authors with UN background and involvement. Focus on UN treaties/declarations and guidance for academics and practitioners in leadership on adopted UN and other international documents. Summarizing the background of the whole-institution approach as a genuine development over time but including limitations and implications for future roles for higher education leadership. IAU SDG 4 Subcluster is unique in its own approach and with its connections to a global network of higher education institutions and UNESCO.

In this work, hafnium oxide layer is investigated as rear surface passivation layer for ultra-thin (550 nm) CIGS solar cells. Point contact openings in the passivation layer are realized by spin-coating potassium fluoride prior to absorber layer growth. Contacts are formed during absorber layer growth and visualized with scanning electron microscopy (SEM). To assess the passivating qualities, HfOx was applied in a metal-insulator-semiconductor (MIS) structure, and it demonstrates a low interface trap density in combination with a negative density of charges. Since we used ultra-thin devices that are ideal to probe improvements at the rear, solar cell results indicated improvements in all cell parameters by the addition of 2 nm thick HfOx passivation layer with contact openings.

Objective This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. Methods Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. Results All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. Conclusion Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). A large annotated dataset, composed of both microscopy and whole-slide images, was specifically compiled and made publicly available for the BACH challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. From the submitted algorithms it was possible to push forward the state-of-the-art in terms of accuracy (87%) in automatic classification of breast cancer with histopathological images. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publically available as to promote further improvements to the field of automatic classification in digital pathology., Accepted for publication at Medical Image Analysis (Elsevier). Publication licensed under the Creative Commons CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Medical devices are an essential part of the delivery of high-quality healthcare to patients all across Europe. In many countries, their procurement and management in the hospital setting falls often under the authority of hospital pharmacists. To further improve the safety of medical devices for European patients, a new regulatory regime was adopted in spring 2017 encompassing both the Medical Device Regulation (MDR) (Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC) and the Invitro Medical Device Regulation(Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU). With the MDR becoming fully applicable from May 2021 onwards, the European Association of Hospital Pharmacists (EAHP) would like to use this occasion to reiterate some of the considerations raised by hospital pharmacist in EAHP’s Statement on the Medical Device Regulation adopted in 2014 and EAHP’s Opinion on this topic released in 2019. EAHP welcomes the reinforcement of the supervision of notified bodies, the strengthened clinical evaluation and the improved surveillance and vigilance mechanisms introduced by the MDR. In relation to the latter, EAHP would like to express its support for the requirements mandating manufacturers to report serious incidents and corrective actions they have taken to reduce the risk of recurrence. However, given that systems for pharmacovigilance reporting by health professionals in respect of medicines are well established across Europe, EAHP would also like to see further empowerment of healthcare professional and patient reporting, in particular, reporting from hospital pharmacists specifically trained for this task. Ensuring reporting processes for devices and medicines are of a similar …

This paper seeks to analyze the impact of terrorism on the enjoyment of civil liberties guaranteed under the European Convention on Human Rights (ECHR). The paper profoundly assesses case law from the European Court of Human Rights (ECtHR) in order to assess how the Court manages to guarantee that rights are still respected and upheld, even when weighed against the most severe circumstances, namely terrorism. In doing so, the counter-terrorism legal system of one of the most controversial parties to the ECHR, the United Kingdom, is assessed to identify issues which arise when combating terrorism. Surveillance and stop-and-search are archetypical anti-terrorism measures that are limited through the ECtHR in order to not excessively infringe upon human rights, in accordance with Lloyd’s notion of imposing sufficient safeguards if new measures are enacted. Although the ECtHR can be considered an essential guarantor for human rights through its judicial dialogues and influences on domestic courts and governments, the issue of refoulment in torture cases must be readdressed in upcoming case-law. Moreover, grave privacy infringements are permitted to a terrifying extent, and the longer the ECtHR takes to take a solid stance against States abusing the aim of national security, the more severe it will naturally become, due to society’s incremental progression towards a digital life. Ultimately, terrorism tests democratic governments in a unique way, as imposing draconian measures would be an easy way to ensure safety. Nonetheless, fighting with one hand behind one’s back is necessary to uphold the status of a rights-respecting democracy. Only time will tell whether the ECtHR will evolve to give proactive verdicts to ensure human rights prior to their breach.