Search

Contains fulltext : 291174.pdf (Publisher’s version ) (Open Access) Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as treatment options are often noncurative and prognosis remains poor. These patients frequently report unprescribed cannabinoid use, presumably for symptom relieve. As studies on brain tumor patients specifically are lacking, we performed a meta-analysis of the current evidence on cannabinoid efficacy on HRQoL and mental well-being in oncological and neurological patients. Methods: We performed a systematic PubMed, PsychINFO, Embase, and Web of Science search according to PRISMA guidelines on August 2 and 3, 2021. We included randomized controlled trials (RCTs) that assessed the effects of tetrahydrocannabinol (THC) or cannabidiol (CBD) on general HRQoL and mental well-being. Pooled effect sizes were calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane's Risk of Bias tool. Results: We included 17 studies: 4 in oncology and 13 in central nervous system (CNS) disease. Meta-analysis showed no effect of cannabinoids on general HRQoL (g=-0.02 confidence interval [95% CI -0.11 to 0.06]; p=0.57) or mental well-being (g=-0.02 [95% CI -0.16 to 0.13]; p=0.81). Conclusions: RCTs in patients with cancer or CNS disease showed no effect of cannabinoids on HRQoL or mental well-being. However, studies were clinically heterogeneous and since many glioma patients currently frequently use cannabinoids, future studies are necessary to evaluate its value in this specific population. 01 februari 2023

© Copyright 2022. Sociedad Meteorológica Estadounidense (AMS). Para obtener permiso para reutilizar cualquier parte de este Trabajo, comuníquese con permisos@ametsoc. org . Cualquier uso del material en este Trabajo que se determine como "uso justo" según la Sección 107 de la Ley de derechos de autor de EE. UU. (17 Código de EE. UU. § 107) o que cumpla las condiciones especificadas en la Sección 108 de la Ley de derechos de autor de EE. ) no requiere el permiso de la AMS. La republicación, la reproducción sistemática, la publicación en forma electrónica, como en un sitio web o en una base de datos de búsqueda, u otros usos de este material, excepto los exentos de la declaración anterior, requieren un permiso por escrito o una licencia de la AMS. Todas las publicaciones periódicas y monográficas de AMS están registradas en el Centro de Autorización de Derechos de Autor (https://www.copyright.com ). Se proporcionan detalles adicionales en la declaración de política de derechos de autor de AMS, disponible en el sitio web de AMS ( https://www.ametsoc.org/PUBSCopyrightPolicy ) ., In 2021, both social and economic activities began to return towards the levels preceding the COVID-19 pandemic for some parts of the globe, with others still experiencing restrictions. Meanwhile, the climate has continued to respond to the ongoing increase in greenhouse gases and resulting warming. La Niña, a phenomenon which tends to depress global temperatures while changing rainfall patterns in many regions, prevailed for all but two months of the year. Despite this, 2021 was one of the six-warmest years on record as measured by global mean surface temperature with an anomaly of between +0.21° and +0.28°C above the 1991–2020 climatology., Lake surface water temperatures from satellite data have been generated within the GloboLakes project funded by the UK National Environment Research Council (NE/J023345/2), with extensions funded by the EU Copernicus Climate Change Service (C3S) programme...

Derzeit entwickelt eine Vielzahl von geförderten Konsortien Anwendungsfälle im Gaia-X-Kontext. Sie sind charakterisiert durch den Nutzen des unternehmensübergreifenden Datenaustauschs. Dennoch wird ein Großteil der Vorhaben keiner bewussten Kosten-Nutzen-Analyse unterzogen. Bestehende Vorgehensmodelle für datenbasierte Geschäftsmodelle berücksichtigen die Interoperabilität nicht. Es fehlt eine ganzheitliche Beschreibung, wie Anwendungsfälle in wettbewerbsfähige Geschäftsmodelle überführt werden. Currently, a number of funded consortia are developing use cases in the Gaia-X context. They are characterised by the benefits of cross-company data exchange. Nevertheless, the majority of the projects are not subjected to a conscious cost-benefit analysis. Existing process models for data-based business models do not take interoperability into account. There is no holistic description of how use cases are transformed into competitive business models.

Cold-start emissions of the sustainable alternative diesel fuel OME are predominantly NOx, formaldehyde, formic acid and unburned OME. Electrical heating in combination with fuel dosing is an effective method for after-treatment system heating.

Since 01/2018, AVOS (ambulant vor stationär = outpatient to inpatient) regulation has been progressively implemented in hernia surgery in Switzerland. The aim of this prospective, observational, two-centre comparative study was to compare the outcome of outpatient and inpatient post-operative care in terms of AVOS by examining the re-admission rate, complication rate and quality of life in patients with primary unilateral inguinal hernia repair.The study ran between 01/2019 and 04/2020 and included 237 patients with a primary unilateral inguinal hernia. Treatment setting was decided according to AVOS guidelines. Primary endpoint was re-admission rate within 6 weeks postoperatively. Secondary endpoints were the complication rate and patient outcome (quality of life) at 6 weeks follow-up postoperatively, as measured by the Short Form 36 Health Survey Questionnaire (SF-36).Complications occurred in 11 (14%) inpatient patients, but none required re-admitting for revision until follow-up at 6 weeks after discharge. In the outpatient group, there were 27 (17%) complications reported, while 6 (4%) of these patients crossed over to the inpatient group immediately after surgery. None of the other complications required re-admission until follow-up at 6 weeks. No significant relationship between treatment setting and number of complications/re-admission rate (p=0.458, p=0.061) was observed. The mean outcome (SF-36) between the treatment groups was not significantly different (p=0.16-0.856).In terms of AVOS selection criteria in Switzerland, primary unilateral inguinal hernia can be safely treated in both treatment settings. Re-admission rates, complications and quality of life do not significantly differ. Day surgery in terms of AVOS might be as effective and efficient, both from the patient's perspective and that of the institution.NCT05234242.

Operations require collaboration between surgeons, anaesthetia professionals, and nurses. The aim of this study was to determine whether intraoperative briefings influence patient outcomes.In a before-and-after controlled trial (9 months baseline; 9 months intervention), intraoperative briefings were introduced in four general surgery centres between 2015 and 2018. During the operation, the responsible surgeon (most senior surgeon present) briefed the surgical team using the StOP? protocol about: progress of the operation (Status), next steps (Objectives), possible problems (Problems), and encouraged asking questions (?). Differences between baseline and intervention were analysed regarding surgical-site infections (primary outcome), mortality, unplanned reoperations, and duration of hospital stay (secondary outcomes), using inverse probability of treatment (IPT) weighting based on propensity scores.In total, 8256 patients underwent surgery in the study. Endpoint data were available for 7745 patients (93.8 per cent). IPT-weighted and adjusted intention-to-treat analyses showed no differences in surgical-site infections between baseline and intervention (9.8 versus 9.6 per cent respectively; adjusted difference (AD) -0.15 (95 per cent c.i. -1.45 to 1.14) per cent; odds ratio (OR) 0.92, 95 per cent c.i. 0.83 to 1.15; P = 0.797), but there were reductions in mortality (1.6 versus 1.1 per cent; AD -0.54 (-1.04 to -0.03) per cent; OR 0.60, 0.39 to 0.92; P = 0.018), unplanned reoperations (6.4 versus 4.8 per cent; AD -1.66 (-2.69 to -0.62) per cent; OR 0.72, 0.59 to 0.89; P = 0.002), and fewer prolonged hospital stays (21.6 versus 19.8 per cent; AD -1.82 (-3.48 to -0.15) per cent; OR 0.87, 0.77 to 0.98; P = 0.024).Short intraoperative briefings improve patient outcomes and should be performed routinely.Outcomes of surgery depend on patient characteristics and surgeon expertise, but also on teamwork, notably communication. The present study introduces the StOP? protocol, in which the surgeon informs the team about the current status (St), objectives regarding next steps (O), and potential problems (P), and encourages the team to ask questions and raise concerns (?). The results suggest an effect of the StOP? intervention on patient mortality, risk of unplanned reoperation, and duration of hospital stay, but not on surgical-site infections. The study is promising regarding the effect of structured intraoperative communication on important patient outcomes. The study compared patient outcomes at baseline and after implementation of the StOP? protocol, which enhances exchange of structured information within the interdisciplinary surgical team during the course of the operation. The intention-to-treat analyses in this multicentre before-and-after study of 8256 patients undergoing general surgery showed no differences between baseline and intervention for surgical-site infections, but revealed reduced mortality and unplanned reoperations, and fewer prolonged hospital stays during the intervention period.

Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.

Global Climate is one chapter from the State of the Climate in 2019 annual report and is avail- able from https://doi.org/10.1175/BAMS-D-20-0104.1 Compiled by NOAA’s National Centers for Environmental Information, State of the Climate in 2019 is based on contributions from scien- tists from around the world. It provides a detailed update on global climate indicators, notable weather events, and other data collected by environmental monitoring stations and instru- ments located on land, water, ice, and in space. The full report is available from https://doi.org/10.1175/2020BAMSStateoftheClimate.1.

Static pelvic tilt impacts functional cup position in total hip arthroplasty (THA). In the current study we investigated the effect of kinematic pelvic changes on cup position. In the course of a prospective controlled trial postoperative 3D-computed tomography (CT) and gait analysis before and 6 and 12 months after THA were obtained in 60 patients. Kinematic pelvic motion during gait was measured using Anybody Modeling System. By fusion with 3D-CT, the impact of kinematic pelvic tilt alterations on cup anteversion and inclination was calculated. Furthermore, risk factors correlating with high pelvic mobility were evaluated. During gait a high pelvic range of motion up to 15.6° exceeding 5° in 61.7% (37/60) of patients before THA was found. After surgery, the pelvis tilted posteriorly by a mean of 4.0 ± 6.6° (p < .001). The pelvic anteflexion led to a mean decrease of −1.9 ± 2.2° (p < .001) for cup inclination and −15.1 ± 6.1° (p < .001) for anteversion in relation to the anterior pelvic plane (APP). Kinematic pelvic changes resulted in a further change up to 2.3° for inclination and up to 12.3° for anteversion. In relation to the preoperative situation differences in postoperative cup position ranged from −4.4 to 4.6° for inclination and from −7.8 to 17.9° for anteversion, respectively. Female sex (p < .001) and normal body weight (p < .001) correlated with high alterations in pelvic tilt. Kinematic pelvic changes highly impact cup anteversion in THA. Surgeons using the APP as reference should aim for a higher anteversion of about 15° due to the functional anteflexion of the pelvis during gait.

Gletscher gibt es in Deutschland nur in dem sehr kleinen Alpenanteil und dort nur an wenigen, für die Eismassen günstigen Stellen. Diese Gletscher sind vermutlich keine Relikte der letzten Eiszeit, sondern Reste der kühleren Phasen der letzten Jahrhunderte. Trotzdem ging von diesen verbliebenen Eisreserven seit dem Beginn der touristischen Erschließung der Alpen eine große Faszination aus, da sie teilweise vom Tal aus zu sehen, oder verhältnismäßig leicht zu erreichen waren. Selbst heute noch kann man auf dem nördlichen Schneeferner den einzigen Gletscherskilift in Deutschland erleben, wenngleich auch dort die Gletscherflächen erheblich zurückgegangen sind. Die frühe Aufmerksamkeit führte auch dazu, dass es viele historische Dokumente über diese Gletscher gibt und so zumindest ihre Veränderung seit dem Ende der kleinen Eiszeit gut dokumentiert ist. Heute sind fast alle der bayerischen Gletscher am Rande ihrer Existenz und es ist nur eine Frage der Zeit, bis der deutsche Alpenraum eisfrei wird. Wir versuchen mit diesem Beitrag die Entwicklung der Gletscher seit den ersten Untersuchungen zu dokumentieren.

Current legislations typically characterize systems of aerosols, such as from vehicle exhaust, primarily by number concentration and size distributions. While potential health threats have a dependence on the particle size, the chemical composition of particles, including the volatile and semi-volatile components adsorbed onto nonvolatile particle cores present at roadside and urban settings, is important in understanding the impact of exhaust particles on health. To date, the only tools suitable for an online in-depth chemical aerosol characterization are aerosol mass spectrometers, which are typically composed of complex and cost intensive instrumentation. We present a new analytical system, which combines a novel inexpensive infrared-radiation-based evaporation system (HELIOS) with a commercially available highly efficient atmospheric ionization source (SICRIT) connected to a rather low-price ion-trap mass spectrometer. Our inexpensive, robust and mobile aerosol characterization HELIOS/SICRIT/Mass Spectrometry system enables highly sensitive chemical analysis of particle-associated volatile substances. We validate the HELIOS/SICRIT/Mass Spectrometry system in laboratory experiments with coated particles generated under controlled conditions, and show that the system is capable of identification of combustion-generated polycyclic aromatic hydrocarbons and relative quantification of individual chemical species adsorbed on particle surfaces. We then employ our system to analyze real-world vehicle engine exhaust aerosol and show through time-resolved measurements with high time resolution (

Infections are a severe complication after an artificial joint replacement. The clinical symptoms are highly variable, particularly in patients with inflammatory rheumatic diseases, which often makes the diagnosis difficult. In addition to clinical and laboratory findings, joint puncture is an essential component of the diagnostics and enables the identification of pathogens. Treatment of periprosthetic infections in patients with rheumatism should be an interdisciplinary cooperation between surgeons, rheumatologists and specialists for infectious diseases. The two essential pillars of treatment are surgical intervention and antibiotics. For acute joint infections an attempt at preservation of the artificial joint can be carried out, whereas for chronic infection situations only replacement of the prosthesis is possible as a curative treatment. In order to reduce the probability of occurrence of a joint infection, modifiable risk factors should be preoperatively identified and specifically treated.

Solution combustion synthesis followed by annealing in air led to the MPTB‐related phosphates (Rh1/6W5/6O3)8(PO2)4, (Ir1/6W5/6O3)8(PO2)4 (a=5.258(2) Å, b=6.538(3) Å, c=17.322(8) Å), (Rh1/9W8/9O3)12(PO2)4 and (Rh2/21W19/21O3)14(PO2)4. Single‐crystals of the mixed‐metal (Rh,W)‐MPTBs at m=4 and at m=7 were grown by chemical vapor transport (CVT). Their crystal structures have been refined from X‐ray single‐crystal data {(Rh,W)‐MPTB at m=4: P212121, Z=1, a=5.2232(3) Å, b=6.4966(3) Å, c=17.3819(9) Å, R1=0.032, wR2=0.075 for 1714 unique reflections, 1524 with Fo>4σ(Fo), 66 variables, 1 constraint, composition from refinement (Rh0.15W0.85O3)8(PO2)4; (Rh,W)‐MPTB at m=7: P21/n, Z=1, a=5.2510(4) Å, b=6.4949(5) Å, c=26.685(2) Å, β=90.30(1)°, R1=0.060, wR2=0.163 for 2074 unique reflections, 1894 with Fo>4σ(Fo), 100 variables, comp. from ref. (Rh0.07W0.93O3)14(PO2)4}. These structure refinements show unexpected distribution of Rh and W over the available metal sites. Further characterization (powder reflectance and magnetic measurements) of the (Rh,W)‐MPTB at m=4 and at m=7 suggest for both phases a homogeneity range with respect to the Rh/W ratio and the presence of small amounts of W5+ besides Rh3+ and W6+. Results of the ligand field analysis for the reference material Rh(PO3)3, which is containing the octahedral chromophore [RhIIIO6], are reported (Δo=23200 cm−1, B=490 cm−1).

Introduction Pancreatic adenocarcinoma (PAC) is a highly malignant tumor with relevant morbidity and mortality. The role of adjuvant chemoradiotherapy (CRT) for primarily resected tumors remains controversial. We aimed to assess the outcome of patients treated at our institution with postoperative CRT for PAC. Methods We present a retrospective case series of patients with pancreatic adenocarcinoma at a single center in Switzerland. These patients were treated by primary surgery followed by adjuvant CRT between 1995 and 2015. The results were compared with published data. Results Median follow-up for the 60 patients was 33 months (range 19.9–193.9); median overall survival (OS) for patients undergoing a resection followed by combined CRT was 25.5 months. Overall, disease-free survival (DFS) was 15.2 months. A local recurrence occurred in 14 patients (23.3%) after a median time of 8.8 months, and in 43 patients (71.7%) distant metastasis was demonstrated with a median time to metastasis of 10.6 months. Conclusion This retrospective study represents one of the sole reviews of outcome data after adjuvant CRT in resected PAC in Europe within the past years. OS was comparable to that of other institutional outcome data published previously but inferior when compared to most recent published results with an intense chemotherapy. However, not all patients are suitable to undergo such an intense chemotherapy with modified FOLFIRINOX after the extensive surgery for the PAC – these patients could benefit from adding adjuvant CRT to a less intensive chemotherapy with gemcitabine to enhance the benefit regarding locoregional recurrence-free survival.

The optimal 3D positioning of the prosthesis components is of great importance for the stability and function of a total hip endoprosthesis. Pelvic tilt has a particular influence on the position of the implant. In order to use intraoperatively the knowledge on pelvic kinematics gained through preoperative imaging procedures and movement analyses, "image-based" and "image-free" robotic and navigation procedures are available. With the "image-based" procedures, a 3D CT scan serves as the surgeon's basis for operative planning. The "image-free" procedures are based on the principles of stereotaxy. In the future, information about static and dynamic pelvic tilt will be conntected with navigation and robotic systems for total hip arthroplasty. Along with intraoperative data a patientindividual optimized implant position can be achieved.

Despite the broad implications of the cannabinoid type 2 receptor (CB2) in neuroinflammatory processes, a suitable CB2-targeted probe is currently lacking in clinical routine. In this work, we synthesized 15 fluorinated pyridine derivatives and tested their binding affinities toward CB2 and CB1. With a sub-nanomolar affinity (Ki for CB2) of 0.8 nM and a remarkable selectivity factor of >12,000 over CB1, RoSMA-18-d6 exhibited outstanding in vitro performance characteristics and was radiofluorinated with an average radiochemical yield of 10.6 ± 3.8% (n = 16) and molar activities ranging from 52 to 65 GBq/μmol (radiochemical purity > 99%). [18F]RoSMA-18-d6 showed exceptional CB2 attributes as demonstrated by in vitro autoradiography, ex vivo biodistribution, and positron emission tomography (PET). Further, [18F]RoSMA-18-d6 was used to detect CB2 upregulation on postmortem human ALS spinal cord tissues. Overall, these results suggest that [18F]RoSMA-18-d6 is a promising CB2 PET radioligand for clinical translation.

A change in our current approach toward drug development is required to improve the likelihood of finding effective treatment for patients with amyotrophic lateral sclerosis (ALS). The aim of the Treatment Research Initiative to Cure ALS (TRICALS) is to extend the collective effort with industry and consolidate drug development paths. TRICALS has begun a series of meetings on how to best move the field forward collaboratively, thereby addressing five major topics in ALS clinical trials: (1) preclinical research, (2) biomarker development, (3) eligibility criteria, (4) efficacy endpoints and (5) innovative trial design. There is an appetite for ongoing discussions of these major topics in clinical trials between representatives from academia, patient advocacy groups, industry partners and funding bodies. Industry is open to fundamentally change drug development for ALS and shorten the time to effective therapy for patients by implementing promising innovations in biomarker development, trial design, and patient selection. There is however, a pressing need from all stakeholders for regulatory discussions and amendments of current guidelines to successfully adopt innovation in future clinical development lines. ispartof: AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION vol:21 issue:7-8 pages:496-501 ispartof: location:England status: published

BackgroundThe Gold Coast criteria (GCC) have been proposed as a means of selecting patients for amyotrophic lateral sclerosis (ALS) clinical trials. We aimed to characterise disease progression according to the GCC.MethodsData from population-based ALS registries from the Netherlands and Belgium were analysed. The GCC additionally define ALS as lower motor neuron (LMN) dysfunction in ≥2 body regions without upper motor neuron dysfunction. Therefore, the revised El Escorial criteria (rEEC) were supplemented with a ‘Gold Coast ALS’ category for patients with only LMN dysfunction in ≥2 body regions. We assessed survival time, ALS Functional Rating Scale (ALSFRS-R) progression rates and between-patient variability per diagnostic category.ResultsWe included 5957 ALS patients, of whom 600 (10.1%) fulfilled the GCC but not the rEEC, and 95 (1.6%) fulfilled only the rEEC. ALSFRS-R progression rates were similar for the rEEC (0.84 points/month) and GCC (0.81 points/month) with similar variability (standard deviation of 0.59 vs. 0.60) and median survival time (17.8 vs.18.7 months). Survival time and average progression rates varied (pConclusionsThe GCC broaden the definition of ALS, allowing more patients to participate in trials, while minimally impacting population heterogeneity. Given the large variability per diagnostic category, selecting only specific categories for trials may not result in a more homogeneous study population.

Objective Male sex is controversially discussed as a risk factor for surgical site infections (SSI). The aim of the present study was to evaluate the impact of sex on SSI in abdominal surgery under elimination of relevant confounders. Methods Clinicopathological data of 6603 patients undergoing abdominal surgery from a multi-center prospective database of four Swiss hospitals including patients between 2015 and 2018 were assessed. Patients were stratified according to postoperative SSI and risk factors for SSI were identified using univariate and multivariate analysis. Results In 649 of 6603 patients, SSI was reported (9.8%). SSI was significantly associated with reoperation (22.7% vs. 3.4%, p p 75th percentile (57.0% vs. 17.9%, p p = 0.01). In multivariate analysis including multiple confounders’ such as comorbidities and perioperative factors, there was no association between male sex and risk of SSI (odds ratio (OR) 1.1 [CI 0.8–1.4]). Independent risk factors for SSI in multivariate analysis were BMI ≥ 30 kg/m2 (OR 1.8 [CI 1.3–2.3]), duration of surgery > 75th percentile (OR 2.3 [1.8–2.9]), high contamination level (OR 1.3 [1.0–1.6]), laparotomy (OR 1.3 [1.0–1.7]), previous laparotomy (OR 1.4 [1.1–1.7]), blood transfusion (OR 1.7 [1.2–2.4]), cancer (OR 1.3 [1.0–1.8] and malnutrition (OR 2.5 [1.8–3.4]). Conclusion Under elimination of relevant confounders, there is no significant correlation between sex and risk of SSI after abdominal surgery.

Background Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. Methods We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. Results The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182–372}] in DBD recipients and 24.5 years [289 months (95% CI 245–333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (–0.6 versus –0.3 mL/min/year) between the two groups for graft survival >20 years. Conclusions This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts.

The genetic basis of amyotrophic lateral sclerosis (ALS) is still incompletely understood. Using two independent genetic strategies, we show here that a large part of ALS heritability lies in genes expressed in inhibitory and excitatory neurons, especially at splicing sites regulated by a defined set of RNA binding proteins including TDP-43 and FUS. We conducted a transcriptome wide association study (TWAS) and identified 59 loci associated with ALS, including 14 previously identified genes, some of them not previously reaching significance in genome wide association studies. Among the 45 novel genes, several genes are involved in pathways known to be affected in ALS such as mitochondrial metabolism (including ATP5H, ATP5D, BCS1L), proteostasis (including COPS7A, G2E3, TMEM175, USP35) or gene expression and RNA metabolism (including ARID1B, ATXN3, PTBP2, TAF10). Interestingly, decreased expression of NUP50, a constrained gene encoding a nuclear pore basket protein, was associated with ALS in TWAS (Zscore = −4, FDR = 0.034). 11 potentially pathogenic variants (CADD score > 20) in 23 patients were identified in the NUP50 gene, most of them in the region of the protein mediating interaction with Importin alpha, and including 2 frameshift mutations. In cells from two patients carrying NUP50 variants, we showed decreased levels of NUP50 protein. Importantly, knocking down Nup50 led to increased neuronal death associated with p62 and nucleoporin inclusions in cultured neurons, and motor defects in Drosophila and zebrafish models. In all, our study identifies alterations in splicing in neurons as a critical pathogenic process in ALS, uncovers several new loci potentially contributing to ALS missing heritability, and provides genetic evidence linking nuclear pore defects to ALS.

Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases., peer-reviewed

In der postoperativen Rontgenkontrolle nach Huft-TEP-Implantation erfolgt durch die Bestimmung der Komponentenstellung eine objektivierbare Qualitatskontrolle. Die Pfannenposition wird hierbei durch die Steilheit und die Drehung nach vorne beschrieben. Zwischen den radiographisch gemessenen Werten und der tatsachlichen (anatomischen) Pfannenstellung besteht jedoch eine Diskrepanz, die zu Fehlinterpretationen fuhren kann. Um die Diskrepanz zwischen tatsachlicher und radiographisch vermessener Pfannenstellung bildlich darzustellen, wurde in dem Video ein Pfannenhalter verwendet, an dem die Drehung nach vorne und die Pfannensteilheit winkelgenau eingestellt werden kann. Hierdurch kann die Pfannenposition (Anteversion und Inklination) in der radiographischen und anatomischen Definition naher erlautert werden. Der Zuschauer soll einen Eindruck bekommen, ab wann die radiologisch gemessenen Werte nur mit groser Vorsicht zu betrachten sind. In dem Video zeigt sich in der simulierten Rontgen- und Bildsequenz, dass bei gleichbleibender tatsachlicher Pfannensteilheit am Modell mit zunehmender Anteversion uber 20° die Inklination radiographisch flacher gemessen wird. Alleiniges Betrachten der radiographischen Winkelwerte der Anteversion und Inklination kann zu Fehlinterpretationen der tatsachlichen Pfannenstellung fuhren. In bildlicher Darstellung zeigen wir, dass eine unterschiedliche Pfannensteilheit und -drehung anhand der radiographischen Messwerte nicht sicher erkannt werden kann. Die wahre Pfannenposition in der anatomischen Definition lasst sich aus der radiographischen Position errechnen. Hierzu mussen jedoch beide Pfannenwerte (rad. Anteversion und rad. Inklination) berucksichtigt werden.

The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [

This article presents a new design for setting up high speed synchronous reluctance motors (SynRM) in motor spindle applications for up to 30,000 rpm. The transversal laminated SynRM rotor package is supported by thin steel sheets and a shaft nut to exert a constant axial clamping force. Both, numerical and practical investigations are carried out using FEM-analysis and a test bench for centrifugal force load tests. The objective is to find out at which speed the elastic deformation changes into the plastic deformation. The beginning of plastic deformation is a failure criterion in electric motor construction.

ObjectiveA hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.MethodsA panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.ResultsThe 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1WT in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1WT inclusions. Minute amounts of misSOD1WT inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1D90A mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.Conclusions and relevanceAbundant inclusions containing misfolded SOD1WT are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1WT can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.

Objective There is still insufficient knowledge about natural history in adult spinal muscular atrophy, thus valid markers for treatment and disease monitoring are urgently needed. Methods We studied hand muscle innervation pattern of 38 adult genetically confirmed 5q spinal muscular atrophy (SMA) patients by the motor unit number index (MUNIX) method. Data were compared to healthy controls and amyotrophic lateral sclerosis (ALS) patients and systematically correlated to typical disease-relevant scores and other clinical as well as demographic characteristics. Results Denervation of hand muscles in adult SMA was not evenly distributed. By calculation of the MUNIX ratios, we identified a specific hand muscle wasting pattern for SMA which is different to the split hand in ALS. Furthermore, MUNIX parameters strongly correlated with established disease course parameters independent of disease stages. Conclusion We found a pathophysiological remarkable denervation pattern of hand muscles, a ‘reversed split hand’. MUNIX of single hand muscles correlated well with disease severity and thus represents an easily available biomarker for adult SMA. Significance Our data show the power of the MUNIX method as a biomarker for upcoming questions in adult SMA.

Background Computed tomography (CT) is the gold standard for the accurate measurement of cup inclination and anteversion in total hip arthroplasty (THA). However, functional cup position strongly depends on the tilt of the pelvis and thus pelvic tilt in the supine position on the CT table harbors the risk of misinterpretation. Purpose To evaluate the influence of pelvic tilt on cup measurements in postoperative CT scans. Material and Methods This is a secondary outcome analysis of a prospective study. In 123 patients undergoing THA, anatomic cup inclination and anteversion as measured on postoperative 3D-CT scans were compared between: (i) the anterior pelvic plane (APP) resembling neutral pelvic tilt; and (ii) the coronal plane representing the standard planes on CT. Furthermore, the effect of the variation on cup positions within Lewinnek’s safe zone in relation to the applied reference plane was assessed. Results Mean pelvic tilt in supine position was –3.5° ± 5.6°. This resulted in a mean difference for anteversion between APP und coronal plane of 2.1° ± 3.7° and of 2.1° ± 1.9° for cup inclination, respectively. The change varied up to 20.2° for cup inclination and up 12.2° for cup anteversion. The overall conversion rate for inclination and/or anteversion regarding Lewinnek’s safe zone was high at 23.6% (29/123). Conclusion Pelvic tilt affects cup orientation on CT scans depending on the applied reference plane. Standard CT planes should be corrected regarding pelvic tilt before measurements to avoid errors in measurement.

The plug-and-play hyphenation of UV-laser ablation (LA) and mass spectrometry is presented, using dielectric barrier discharge ionization (DBDI). The DBDI source employed here is characterized by its unique geometry, being directly mounted onto the inlet capillary of a mass spectrometer. In the literature, this particular kind of DBDI source is also referred to as active capillary plasma ionization. It has been commercialized as soft ionization by chemical reaction in transfer (SICRIT) and will be addressed as DBDI in this study. LA-DBDI-MS was used for the direct, molecule-specific and spatially resolved analysis of various solid samples, such as coffee beans and pain killer tablets without extensive sample preparation. The combination of fast washout UV-laser ablation and the principle of the DBDI source used here allowed for highly efficient soft ionization as well as high spatial resolution down to 10 μm for molecular imaging.

Introduction The Hospital Frailty Risk Score (HFRS) is a validated risk stratification model referring to the cumulative deficits model of frailty. The purpose of this study was to evaluate the HFRS as a predictor of 90-day readmission and complications after revision total hip (rTHA) and knee (rTKA) arthroplasty. Methods In a retrospective analysis of 565 patients who had undergone rTHA or rTKA between 2011 and 2019, the HFRS was calculated for each patient. Rates of adverse events were compared between patients with low and intermediate or high frailty risk. Multivariable logistic regression models were used to assess the relationship between the HFRS and post-operative adverse events. Results Patients with intermediate or high frailty risk showed higher rates of readmission (30days: 23.8% vs. 9.9%, p = 0.006; 90days: 26.2% vs. 13.0%, p < 0.018), surgical complications (28.6% vs. 7.8%, p < 0.001), medical complications (11.9% vs. 1.0%, p < 0.001), other complications (28.6% vs. 2.3%, p < 0.001), Clavien-Dindo grade IV complications (14.3% vs. 4.8%, p = 0.009), and transfusion (33.3% vs. 6.1%, p < 0.001). Multivariable logistic regression analyses revealed a high HFRS as independent risk factor for surgical complications (OR = 3.45, 95% CI 1.45-8.18, p = 0.005), medical complications (OR = 7.29, 95% CI 1.72-30.97, p = 0.007), and other complications (OR = 14.15, 95% CI 5.16-38.77, p < 0.001). Conclusion The HFRS predicts adverse events after rTHA and rTKA. As it derives from routinely collected data, the HFRS could be implemented automated in hospital information systems to facilitate identification of at-risk patients.

Background and purpose — There is growing evidence that hypoproteinemia is an important risk factor for adverse events after surgery. Less is known about the impact of vitamin deficiency on postoperative outcome. Therefore we evaluated the prevalence and impact of malnutrition and vitamin deficiency in geriatric patients undergoing elective orthopedic surgery. Patients and methods — In a retrospective analysis of 599 geriatric patients who had undergone elective orthopedic surgery in 2018 and 2019, hypoproteinemia, and deficiency of vitamin D, vitamin B12, and folate were assessed. Reoperation rates, readmission rates, complication rates, and transfusion rates were compared between malnourished patients and patients with normal parameters. Multivariable logistic regression models were used to assess the relationship between malnutrition and postoperative adverse events, controlling for confounding factors such as age, sex, diabetes mellitus, and frailty. Results — Patients with malnutrition showed a higher rate of reoperation (13% vs. 5.5%; p = 0.01) and exhibited more wound-healing disorders (7.4% vs. 1.3%, p = 0.001) as well as Clavien–Dindo IV° complications (7.4% vs. 2.4%; p = 0.03). Deficiency of vitamin D led to a higher rate of falls (8.4% vs. 2.9%, p = 0.006). Deficiency of vitamin B12 and folate did not affect postoperative adverse events. Although correlated to frailty (p = 0.004), multivariable regression analysis identified malnutrition as independent risk factor for reoperation (OR 2.6, 95% CI 1.1–6.2) and wound healing disorders (OR 7.1, CI 1.9–26). Interpretation — Malnutrition is common among geriatric patients undergoing elective orthopedic surgery and represents an independent risk factor for postoperative adverse events.

Background and purpose ��� Improving health care and demographic change have resulted in a steady increase in geriatric patients undergoing total hip (THA) and knee (TKA) arthroplasty. Postoperative delirium (POD) is a frequent and severe complication after major surgery. Therefore, we analyzed the impact of POD on outcome after THA and TKA. Patients and methods ��� In a consecutive series of 10,140 patients who had undergone elective THA or TKA between 2011 and 2020, rates of reoperation within 90 days, readmission within 90 days, complications, and responder rate as defined by the OMERACT-OARSI criteria were compared between patients with and without POD. Multivariable logistic regression models were used to assess the relationship between POD and other postoperative complications. Results ��� Patients with POD showed higher rates of reoperation (12% vs. 5%), readmission (15% vs. 5%), surgical complications (7% vs. 2%), non-surgical complications (8% vs. 4%), Clavien���Dindo IV�� complications (10% vs. 2%) and transfusion (14% vs. 2%). POD led to lower responder rate (76% vs. 87%) 1 year after total joint replacement. All previous comparisons statistically significant. Multivariable logistic regression analyses revealed POD as an independent risk factor for reoperation (OR = 2; CI 1���3), readmission (OR = 2; CI 2���4) and Clavien���Dindo IV�� complications (OR = 3; CI 2���5). Interpretation ��� POD is a serious problem in elective joint replacement. Affected patients suffer more complications and show poor patient-reported outcome 1 year postoperatively. Systematic prevention strategies and standardized therapy protocols are mandatory to avoid burden to patients and healthcare providers.

Introduction Because of the ongoing discussion of imageless navigation in total knee arthroplasty (TKA), its advantages and disadvantages were evaluated in a large patient cohort. Methods This retrospective analysis included 2464 patients who had undergone TKA at a high-volume university arthroplasty center between 2012 and 2017. Navigated and conventional TKA were compared regarding postoperative mechanical axis, surgery duration, complication rates, one-year postoperative patient-reported outcome measures (PROMs) (WOMAC and EQ-5D indices), and responder rates as defined by the criteria of the Outcome Measures in Rheumatology and Osteoarthritis Research Society International consensus (OMERACT-OARSI). Results Both navigated (1.8 ± 1.6°) and conventional TKA (2.1 ± 1.6°, p = 0.002) enabled the exact reconstruction of mechanical axis. Surgery duration was six minutes longer for navigated TKA than for conventional TKA (p p = 0.39), joint infection (p = 0.42 and thromboembolic events (p = 0.03). Periprosthetic fractures occurred more frequently during conventional TKA (p = 0.001). One-year PROMs showed excellent improvement in both groups. The WOMAC index was statistically higher for navigated TKA than for conventional TKA (74.7 ± 19.0 vs. 71.7 ± 20.7, p = 0.014), but the increase was not clinically relevant. Both groups had a similarly high EQ-5D index (0.23 ± 0.24 vs. 0.26 ± 0.25, p = 0.11) and responder rate (86.5% [256/296] vs. 85.9% [981/1142], p = 0.92). Conclusion Both methods enable accurate postoperative leg alignment with low complication rates and equally successful PROMs and responder rates one year postoperatively. Level of evidence III. Retrospective cohort study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 samples (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.

Background Mesenteric ischemia is associated with poor outcome and high overall mortality. The aim was to analyze an interdisciplinary treatment approach of vascular and visceral specialists focusing on the in-hospital outcome and follow-up in patients with acute and acute-on-chronic mesenteric ischemia. Methods From 2010 until 2017, 26 consecutive patients with acute or acute on chronic mesenteric ischemia were treated by an interdisciplinary team. Data were prospectively collected and retrospectively evaluated. Throughout the initial examination, the extent of bowel resection was determined by the visceral surgeon and the appropriate mode of revascularization by the vascular surgeon. The routine follow-up included clinical examination and ultrasound- or CT-imaging for patency assessment and overall survival as primary endpoint of the study. Results Out of 26 patients, 18 (69.2%) were rendered for open repair. Ten patients (38.5%) received reconstruction of the superior mesenteric artery with an iliac-mesenteric bypass. Seven patients (26.9%) underwent thrombembolectomy of the mesenteric artery. One patient received an infra-diaphragmatic aorto-celiac-mesenteric bypass. Out of the 8 patients, who were not suitable for open revascularization, 2 patients (7.7%) were treated endovascularly and 6 (23.1%) underwent explorative laparotomy. The in-hospital mortality was 23% (n = 6). The mean survival of the revascularized group (n = 20) was 51.8 months (95% CI 39.1–64.5) compared to 15.7 months in the non-revascularized group (n = 6) (95% CI − 4.8–36.1; p = 0.08). The median follow-up was 64.6 months. Primary patency in the 16 patients after open and 2 after interventional revascularization was 100% and 89.9% in the follow-up. Conclusion The interdisciplinary treatment of mesenteric ischemia improves survival if carried out in time. Hereby open revascularization measures are advantageous as they allow bowel assessment, resection, and revascularization in a one-stop fashion especially in advanced cases.

Micro Electro Mechanical Semiconductors (MEMS) functionalities have been continuously extended during the last years, and they are applied in a wide range of industrial sectors, including the automotive, consumer electronics, and Internet of Things (IoT) markets. These MEMS sensor packages are a multi-materials composite system. The composite materials involved in MEMS sensor packages show significant effects like thermal expansion and hygroscopic swelling when exposed to environmental loads like temperature and moisture. Due to these effects, the MEMS sensing performance is affected. To understand the effects on sensing performance and mechanical behavior, an advanced simulation approach, “hygro-thermo-mechanical simulation,” needs to be accounted for. This approach considers not only the dynamic changes in temperature and moisture loads but also generalized solubility, which is a function of both temperature and saturated mass concentration. This numerical model helps in optimizing and understanding the sensing performance of the MEMS sensor packages.