Search

The unconventional Wire Electric Discharge Machining (WEDM) technology represents a vital manufacturing technology in different industrial branches. This technology is essential because of the possibility to machine difficult-to-machine materials such as sintered carbides. For this reason, this study analyses the machinability of sintered carbides WKP23S, WSM33S a WK1 with WEDM in both water and oil baths. We investigated the influence of the machining parameters, namely, pulse off time, gap voltage, discharge current, pulse on time, and wire feed, on the cutting speed, surface roughness, and defect occurrence. We investigated 9 different roughness parameters, analysed surface morphology with an electron microscope, and also analysed cross-sectioned samples. We found out that machining sintered carbides in oil bath yields better results than machining in deionized water. The oil tank prevents the removal of the cobalt binder, but it doesn’t reduce fissure occurrence in any significant way.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound to clonal copies of DNA targets. These polymer–nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

Numerical simulations of the cardiovascular system are growing in popularity due to the increasing availability of computational power, and their proven contribution to the understanding of pathodynamics and validation of medical devices with in-silico trials as a potential future breakthrough. Such simulations are performed on volumetric meshes reconstructed from patient-specific imaging data. These meshes are most often unstructured, and result in a brutally large amount of elements, significantly increasing the computational complexity of the simulations, whilst potentially adversely affecting their accuracy. To reduce such complexity, we introduce a new approach for fully automatic generation of higher-order, structured hexahedral meshes of tubular structures, with a focus on healthy blood vessels. The structures are modeled as skeleton-based convolution surfaces. From the same skeleton, the topology is captured by a block-structure, and the geometry by a higher-order surface mesh. Grading may be induced to obtain tailored refinement, thus resolving, e.g., boundary layers. The volumetric meshing is then performed via transfinite mappings. The resulting meshes are of arbitrary order, their elements are of good quality, while the spatial resolution may be as coarse as needed, greatly reducing computing time. Their suitability for practical applications is showcased by a simulation of physiological blood flow modelled by a generalised Newtonian fluid in the human aorta.

Background We investigated the feasibility of aneurysm sac embolization using a novel self-expanding porous shape memory polymer (SMP) device during endovascular aortic abdominal or thoracic aneurysm repair (EVAR). Methods Retrospective analysis of consecutive patients treated at 2 centers in Germany. Patients were treated from January 2019 to July 2021 with follow-up at 7 days and 3, 6, and 12 months. Aneurysm sacs were implanted with SMP devices immediately following endograft placement during the same procedure. Primary endpoint was technically successful SMP-device deployment into the aneurysm sac outside the endograft. Secondary endpoints were changes in aneurysm volume and associated complications (e.g., endoleaks). Results We included 18 patients (16 males), aged 72 ± 9 years, achieving 100% technical success. Mean preprocedure aortic aneurysm sac volume was 195 ± 117 mL with a perfused aneurysm volume of 97 ± 60 mL. A mean of 24 ± 12 SMP devices per patient were used (range 5–45, corresponding to 6.25–56.25 mL expanded embolic material volume). All evaluable patients exhibited sac regression except 2 patients yet to reach 3-month follow-up. At mean 11 ± 7 months (range 3–24), change in aneurysm volume from baseline was -30 ± 21 mL (p Conclusions SMP devices for aortic aneurysm sac embolization during endovascular repair appear feasible and safe in this small case series. Prospective studies are needed. Key points • Shape memory polymer is a novel, self-expanding, porous, and radiolucent embolic device material. • Aortic aneurysm sacs were treated with polymer devices immediately following endograft placement. • Aortic aneurysm sac regression was observed in all patients with over 3-month follow-up. • Aortic aneurysm sac regression was observed even in the presence of endoleaks.

Flow diverter stents (FDS) are well established in the treatment of intracranial aneurysms which are difficult to treat with conventional endovascular techniques. However, they carry a relatively high risk of specific complications compared to conventional stents. A minor but frequent finding is the occurrence of reversible in-stent-stenosis (ISS) that tend to resolve spontaneously over time. Here, we report the case of a patient in their 30s who was treated with FDS for bilateral paraophthalmic internal carotid artery (ICA) aneurysms. ISS were found at the respective early follow-up examinations on both sides and had resolved at the 1-year follow-up examinations. Surprisingly ISS reoccurred at both sides in later follow-up examinations and again resolved spontaneously. The recurrence of ISS after resolution is a finding that has not been described previously. Its incidence and further development should be investigated systematically. This might contribute to our understanding of the mechanisms underlying the effect of FDS.

Purpose The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification. Methods In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper–pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification. Results Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients. Conclusions Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.

BackgroundTemporal distribution shift negatively impacts the performance of clinical prediction models over time. Pretraining foundation models using self-supervised learning on electronic health records (EHR) may be effective in acquiring informative global patterns that can improve the robustness of task-specific models.ObjectiveTo evaluate the utility of EHR foundation models in improving the in-distribution (ID) and out-of-distribution (OOD) performance of clinical prediction models.MethodsThe cohort consisted of adult inpatients admitted between 2009-2021. Gated recurrent unit (GRU)- and transformer (TRANS)-based foundation models were pretrained on EHR of patients admitted between 2009-2012 and were subsequently used to construct patient representations (CLMBR). These representations were used to learn logistic regression models (CLMBRGRU and CLMBRTRANS) to predict hospital mortality, long length of stay, 30-day readmission, and ICU admission. We compared CLMBRGRU and CLMBRTRANS with baseline logistic regression models learned on count-based representations (count-LR) and end-to-end (ETE) GRU and transformer models in ID (2009-2012) and OOD (2013-2021) year groups. Performance was measured using area-under-the-receiver-operating-characteristic curve, area- under-the-precision-recall curve, and absolute calibration error.ResultsModels trained on CLMBR generally showed better discrimination relative to count-LR in both ID and OOD year groups. In addition, they often matched or were better than their ETE counterparts. Finally, foundation models’ performance in the self-supervised learning task tracked closely with the ID and OOD performance of the downstream models.ConclusionsThese results suggest that pretraining foundation models on electronic health records is a useful approach for developing clinical prediction models that perform well in the presence of temporal distribution shift.

Movement is a basic feature of fish ecology, being related to dispersal, recolonization, and recovery of local populations after disturbance. Non-migratory species are the main component of stream fish communities, especially in the Neotropics, but there is little information on the characteristics of their movement. In this capture-recapture study, we describe the individual movement of the armored catfish Rineloricaria aequalicuspis in a stream in southern Brazil. We also assess whether this species displays heterogeneous movement, as well as its degree of mobility and the relationship between individual fish movement and body size and local habitat characteristics. Data on individual fish positions were obtained monthly from November 2018 to March 2019, in ten 20-m stream sections along a 430-m stream stretch. Individual fish were captured by kick sampling and measured, photographed (for later photo-identification), and released back to the stream. The movement frequency distribution was moderately leptokurtic (kurtosis = 3.31), indicating heterogeneous movement with two groups of individuals, stationary and mobile. The maximum movement distances were 248 m and 208 m, downstream and upstream, respectively, while the mean movement distance was 98.6 m. Density of individuals was the main factor affecting the probability of movement, suggesting a role for resource availability and intraspecific interactions. The heterogeneous movement pattern observed for R. aequalicuspis indicates that intra-populational variability in movement behavior occurs in non-migratory stream species, which have been often assumed to be either sedentary or mobile species. We highlight that sedentary behavior should not be assumed a priori for stream fishes, not even for those species usually considered to be of low mobility, as many loricariids.

Artificial intelligence and the underlying machine learning (ML) methods are increasingly finding their way into our working world. One of these areas is sales planning, where machine learning is used to leverage a variety of different input parameters such as prices, promotions, or the weather, to forecast sales, and therefore directly affects the production of products and goods. To satisfy the goal of environmental sustainability as well as address short shelf life, the food industry represents an interesting application field for the use of ML for optimizing sales planning. Within this paper, we will examine the design, and especially the application, of ML methods in the food industry and show the current challenges that exist in the use of such concepts and technologies from the end-user’s point of view. Our study of a smaller bakery company shows that there are enormous challenges in setting up the appropriate infrastructure and processes for the implementation of ML, that the output quality of ML processes does not always match the perceived result quality, and that trust in the functioning of the algorithms is the most important criterion for using ML processes in practice.

Although individual psychotherapy is generally effective for a range of mental health conditions, little is known about the moment-to-moment language use of effective therapists. Increased access to computational power, coupled with a rise in computer-mediated communication (telehealth), makes feasible the large-scale analyses of language use during psychotherapy. Transparent methodological approaches are lacking, however. Here we present novel methods to increase the efficiency of efforts to examine language use in psychotherapy. We evaluate three important aspects of therapist language use - timing, responsiveness, and consistency - across five clinically relevant language domains: pronouns, time orientation, emotional polarity, therapist tactics, and paralinguistic style. We find therapist language is dynamic within sessions, responds to patient language, and relates to patient symptom diagnosis but not symptom severity. Our results demonstrate that analyzing therapist language at scale is feasible and may help answer longstanding questions about specific behaviors of effective therapists.

Zusammenfassung Ziel Ziel der Studie war es, die Zufriedenheit der Mitarbeiterinnen und Mitarbeiter der Universitätsaugenklinik des Saarlandes mit der elektronischen Patientenakte FIDUS zwischen Dezember 2016 und September 2020 zu vergleichen, nachdem sie im Januar 2016 eingeführt worden war. Methoden Um diese Studie durchzuführen, hat das FIDUS-Team der Universitätsaugenklinik des Saarlandes einen Fragebogen erstellt. Dieser wurde im Dezember 2016 und im September 2020 an alle Beteiligten verteilt: ärztliches Personal, Pflege- und Verwaltungspersonal. Der Bogen enthielt 19 Fragen, die auf einer Skala von 0 für („stimme nicht zu“) bis 10 („stimme vollständig zu“) zu beantworten waren. Ergebnisse Die Anzahl der Teilnehmenden hatte von 60 (44 %) auf 89 (64 %) zwischen 2016 und 2020 deutlich zugenommen. Davon waren 23 (25,8 %) dem ärztlichen und 27 (30,3 %) dem pflegerischen Personal zuzuordnen, 12 (13,4 %) waren Verwaltungsbereich, 16 (17,9 %) in einem sonstigen Arbeitsverhältnis, und 11 (12,3 %) machten keine Angabe. Im Jahr 2020 haben 75,6 % der Befragten auf der Skala mit „10“ zugestimmt, dass die Einführung der elektronischen Patientenakte der richtige Schritt war, im Vergleich zu 36,7 % im Jahr 2016 (p p Schlussfolgerung Die Zufriedenheit mit der elektronischen Patientenakte FIDUS hat sich im Jahr 2020 im Vergleich zu 2016 signifikant verbessert. Das gilt insbesondere für die bessere Übersichtlichkeit der Akte und die schnelleren Arbeitsabläufe. Allerdings scheint noch Optimierungsbedarf im Detail zu bestehen.

Student dropout is a multi-causal process. Different theoretical models on student dropout consider dysfunctional study behavior (e.g., academic procrastination) and low study satisfaction as possible determinants of students’ dropout intentions during their university studies. However, these models neglect contemporary conceptualizations that assume reverse relationships between dropout intentions and other determinants of the dropout process. Until now, empirical evidence on these assumptions is scant. The present three-wave longitudinal study explored the reciprocal relationships between academic procrastination, study satisfaction, and dropout intentions over one semester. To this end, we used data of N = 326 undergraduate students enrolled in mathematics and law. Our latent cross-lagged panel model replicated existing empirical cross-sectional findings between the variables (i.e., academic procrastination, study satisfaction, and dropout intentions). Regarding the longitudinal relations, as expected, the cross-lagged effects showed that higher dropout intentions significantly related to subsequent higher academic procrastination and lower study satisfaction. Unexpectedly, academic procrastination did not significantly relate to subsequent dropout intentions. Additionally, higher study satisfaction significantly associated with subsequent higher dropout intentions—possibly due to unfulfilled expectations. Further, higher study satisfaction significantly related to subsequent higher procrastination—possibly due to more confidence among satisfied students. Our results broaden the view on dropout intentions as part of the dynamic interplay of student dropout determinants and the need to refine dropout models’ assumptions accordingly. Practically, realistic expectations seem important to reduce dropout intentions. Further, student counselors should have a closer look at the reasons for academic procrastination to develop individual solutions for this dysfunctional behavior.

Background SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann–Whitney U test. Results Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350–560) vs 359 s (IQR 287–521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p p p Conclusion Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease.

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) is a robotic arm-mounted instrument onboard NASA’s Perseverance rover. SHERLOC combines imaging via two cameras with both Raman and fluorescence spectroscopy to investigate geological materials at the rover’s Jezero crater field site. SHERLOC requires in situ calibration to monitor the health and performance of the instrument. These calibration data are critically important to ensure the veracity of data interpretation, especially considering the extreme martian environmental conditions where the instrument operates. The SHERLOC Calibration Target (SCT) is located at the front of the rover and is exposed to the same atmospheric conditions as the instrument. The SCT includes 10 individual targets designed to meet all instrument calibration requirements. An additional calibration target is mounted inside the instrument’s dust cover. The targets include polymers, rock, synthetic material, and optical pattern targets. Their primary function is calibration of parameters within the SHERLOC instrument so that the data can be interpreted correctly. The SCT was also designed to take advantage of opportunities for supplemental science investigations and includes targets intended for public engagement. The exposure of materials to martian atmospheric conditions allows for opportunistic science on extravehicular suit (i.e., “spacesuit”) materials. These samples will be used in an extended study to produce direct measurements of the expected service lifetimes of these materials on the martian surface, thus helping NASA facilitate human exploration of the planet. Other targets include a martian meteorite and the first geocache target to reside on another planet, both of which increase the outreach and potential of the mission to foster interest in, and enthusiasm for, planetary exploration. During the first 200 sols (martian days) of operation on Mars, the SCT has been analyzed three times and has proven to be vital in the calibration of the instrument and in assisting the SHERLOC team with interpretation of in situ data.

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265, Funder: Chinese Academy of Medical Sciences (CAMS); doi: https://doi.org/10.13039/501100005150, Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

This is the first report of a segmental mediolysis occurring in arterioles, affecting the neck/tonsillar region and leading to a fatal hemorrhage after a tonsillectomy in a 20-year-old woman. Arteriolar mediolysis could be observed in tissue layers about 2 cm distant from the tonsillectomy region. Reparative changes were observed in the carotid and small neck arteries as well as in only one intramyocardial arteriole; however, no other vascular regions typically reported in segmental mediolysis arteriopathy were affected and aneurysm formation was not observed. No family history of vascular disease or hypertension was known. Pathophysiologically, previously reported reasons for post-tonsillectomy bleeding could be excluded. Segmental mediolysis may represent a wider spectrum of affected arteriolar vessels besides the reported small and medium sized arteries leading to aneurysms, which impedes radiographic diagnosis.

Die pachychorioidalen Erkrankungen sind alle durch eine Verdickung der Aderhaut gekennzeichnet. Die Gruppe umfasst die folgenden Krankheitsgruppen: pachychorioidale Pigmentepitheliopathie (PPE), Chorioretinopathia centralis serosa (CCS), pachychorioidale Neovaskulopathie (PNV), polypoidale chorioidale Vaskulopathie (PCV)/aneurysmatische chorioidale Neovaskularisation Typ 1 (ACNV‑1), fokale chorioidale Exkavation (FCE) und peripapillares pachychorioidales Syndrom (PPS). Wenn bei verdickter Aderhaut zusatzlich eine Veranderung des retinalen Pigmentepithels vorliegt, lautet die Diagnose PPE; wenn die verdickte Aderhaut von subretinaler Flussigkeit begleitet ist, lautet die Diagnose CCS; wenn eine chorioidale Neovaskularisation vorliegt, lautet die Diagnose PNV; wenn sie von Aneurysmen begleitet ist, lautet die Diagnose ACNV‑1. PPE, CCS, PNV und ACNV‑1 wurden als unabhangige Krankheitsentitaten angesehen, lassen sich aber als 4 Formen einer einzigen Krankheitsfamilie, der „pachychorioidalen Makulaerkrankung“, klassifizieren.

Die Fortschritte der kardialen Bildgebung und bei den 3‑D-Mappingverfahren haben in der letzten Dekade zu einem signifikanten Erkenntnisgewinn hinsichtlich der Korrelation ventrikularer Extrasystolen (VES) mit anatomischen Strukturen gefuhrt. Bei allem technischen Fortschritt bleibt die Interpretation des 12-Kanal-EKGs Grundlage fur die klinische Praxis. So lasst sich mit fundiertem Grundwissen uber die kardiale Anatomie und Erregungsausbreitung – unter Berucksichtigung der Limitationen der Methode – die Herkunft ventrikularer Ektopien mit hinreichender Genauigkeit bestimmen. Zur groben Eingrenzung reichen bereits wenige Anhaltspunkte. Anhand des Lagetyps kann zwischen einem diaphragmalen Ursprung mit superiorer Achse und einem weiter superior gelegenen Ursprung mit einem nach inferior gerichteten Summationsvektor unterschieden werden. In den Brustwandableitungen kann mit hoher Wahrscheinlichkeit von einem linksventrikularen Ursprung einer Ektopie ausgegangen werden, wenn diese eine Rechtsschenkelblock-Morphologie oder positive Konkordanz zeigt. Eine Linksschenkelblock-Morphologie kann neben dem rechten Ventrikel als Ursprungsort auch das interventrikulare Septum miteinschliesen. Je spater die R/S-Transition der Brustwandableitungen erfolgt, desto weiter anterior ist der Ursprung der VES. Die sich kreuzenden Ausflusstrakte der Ventrikel erschweren eine Lokalisation von VES aus diesem Bereich. Hier gibt v. a. die Form und Hohe der R‑Zacke in V1–V3 einen Aufschluss uber den moglichen Ursprungsort. Unscharfen in der EKG-Lokalisation bestehen insbesondere bei semimobilen Strukturen wie den Papillarmuskeln und dem Moderatorband, mit variablem Verlauf innerhalb der Ventrikel. Auf Basis der so gewonnenen Informationen kann in der Folge eine fundierte Einschatzung uber die Prognose und den zu erwartenden Erfolg einer medikamentosen oder invasiven Therapie getroffen werden.

Leefstijlinterventies bij diabetes type 2 (DM2) blijken op de korte termijn goed te werken. Of ze ook op de langere termijn in ‘real life’-omstandigheden effect hebben is echter nog niet zo duidelijk. De intensieve leefstijlbehandeling Keer Diabetes2 Om van Voeding Leeft blijkt een duurzame gedragsverandering teweeg te brengen. Na 24 maanden gebruikte tweederde van de respondenten die eraan deelnamen minder diabetesmedicatie en was bijna eenderde nog altijd geheel gestopt. Zeven op de 10 respondenten die bij start insuline gebruikten, deden dat na 2 jaar nog steeds niet. De kwaliteit van leven nam toe.

Summary Introduction On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus‑2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. Methods This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. Results A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54–74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49–64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5–11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5–31 days), median hospital LOS was 27 days (IQR 13–49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. Conclusion Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.

Temporal dataset shift associated with changes in healthcare over time is a barrier to deploying machine learning-based clinical decision support systems. Algorithms that learn robust models by estimating invariant properties across time periods for domain generalization (DG) and unsupervised domain adaptation (UDA) might be suitable to proactively mitigate dataset shift. The objective was to characterize the impact of temporal dataset shift on clinical prediction models and benchmark DG and UDA algorithms on improving model robustness. In this cohort study, intensive care unit patients from the MIMIC-IV database were categorized by year groups (2008–2010, 2011–2013, 2014–2016 and 2017–2019). Tasks were predicting mortality, long length of stay, sepsis and invasive ventilation. Feedforward neural networks were used as prediction models. The baseline experiment trained models using empirical risk minimization (ERM) on 2008–2010 (ERM[08–10]) and evaluated them on subsequent year groups. DG experiment trained models using algorithms that estimated invariant properties using 2008–2016 and evaluated them on 2017–2019. UDA experiment leveraged unlabelled samples from 2017 to 2019 for unsupervised distribution matching. DG and UDA models were compared to ERM[08–16] models trained using 2008–2016. Main performance measures were area-under-the-receiver-operating-characteristic curve (AUROC), area-under-the-precision-recall curve and absolute calibration error. Threshold-based metrics including false-positives and false-negatives were used to assess the clinical impact of temporal dataset shift and its mitigation strategies. In the baseline experiments, dataset shift was most evident for sepsis prediction (maximum AUROC drop, 0.090; 95% confidence interval (CI), 0.080–0.101). Considering a scenario of 100 consecutively admitted patients showed that ERM[08–10] applied to 2017–2019 was associated with one additional false-negative among 11 patients with sepsis, when compared to the model applied to 2008–2010. When compared with ERM[08–16], DG and UDA experiments failed to produce more robust models (range of AUROC difference, − 0.003 to 0.050). In conclusion, DG and UDA failed to produce more robust models compared to ERM in the setting of temporal dataset shift. Alternate approaches are required to preserve model performance over time in clinical medicine.

Unter dem Begriff CUP-Syndrom („cancer of unknown primary“) versteht man ein vielgestaltiges Krankheitsbild, bei dem die betroffenen Patienten Lymphknoten- und/oder Fernmetastasen aufweisen, ohne dass die Lokalisation des Primartumors bekannt ist. Die Kriterien des CUP-Syndroms sind erfullt, wenn ein histologisch oder zytologisch gesichertes Malignom vorliegt ohne nachweisbaren Primartumor nach Abschluss der Primardiagnostik. Aufgrund der meist schlechten Prognose und dem mannigfaltigen Erscheinungsbild, welches eine standardisierte Therapie oft nicht ermoglicht, stellt das zervikale CUP-Syndrom spezifische Anforderungen an die klinische und bildgebende Diagnostik. Die Bildgebung nimmt hierbei mittels moderner Techniken wie Positronen-Emissions-Tomographie/Computertomographie (PET/CT) eine Schlusselrolle bei der Detektion eines moglichen, okkulten Primartumors sowie im Rahmen des Stagings und der Prognoseeinschatzung ein.

The world’s first hand transplant was performed for a serviceman in 1964, following a blast injury. Despite a need for such effective reconstruction of military wounds, only eight further transplants have been performed for injured soldiers. This review analysed the specific factors that have informed the use of vascularized composite allotransplantation (VCA) in military patients. Nine servicemembers have received reconstructive transplants worldwide. Seven have received upper limb transplants, one a partial face transplant and one a penile transplant. These have been in Ecuador, the USA, Poland, India and Russia. Countries with clinical VCA programmes in military hospitals include Vietnam and China, whilst others have active pre-clinical VCA research programmes including the USA, the UK and Canada. Despite specific concerns in reconstructing military patients using VCA, outcomes have improved in the last decade and the field has evolved to include more complex tissue composites, across more international centres.

Despite the overwhelming success of vaccines in preventing infectious diseases, there remain numerous globally devastating diseases without fully protective vaccines, particularly human immunodeficiency virus (HIV), malaria and tuberculosis. Nanotechnology approaches are being developed both to design new vaccines against these diseases as well as to facilitate their global implementation. The reasons why a given pathogen may present difficulties for vaccine design are unique and tied to the co-evolutionary history of the pathogen and humans, but there are common challenges that nanotechnology is beginning to help address. In each case, a successful vaccine will need to raise immune responses that differ from the immune responses raised by normal infection. Nanomaterials, with their defined compositions, commonly modular construction, and length scales allowing the engagement of key immune pathways, collectively facilitate the iterative design process necessary to identify such protective immune responses and achieve them reliably. Nanomaterials also provide strategies for engineering the trafficking and delivery of vaccine components to key immune cells and lymphoid tissues, and they can be highly multivalent, improving their engagement with the immune system. This Review will discuss these aspects along with recent nanomaterial advances towards vaccines against infectious disease, with a particular emphasis on HIV/AIDS, malaria and tuberculosis. Several globally significant infectious diseases are not yet treatable with vaccination; nanomaterials are being investigated to provide new strategies for vaccine development.

PURPOSE: To measure the stiffness of the placenta in healthy and preeclamptic patients in the second and third trimesters of pregnancy using ultrasound shear-wave elastography (SWE). We also aimed to evaluate the effect of age, gestational age, gravidity, parity and body mass index (BMI) on placental stiffness and a possible correlation of stiffness with perinatal outcomes. METHODS: In a case–control study, we recruited a total of 47 singleton pregnancies in the second and third trimesters of which 24 were healthy and 23 were diagnosed with preeclampsia. In vivo placental stiffness was measured once at the time of recruitment for each patient. Pregnancies with posterior placentas, multiple gestation, gestational hypertension, chronic hypertension, diabetes, autoimmune disease, fetal growth restriction and congenital anomalies were excluded. RESULTS: The mean placental stiffness was significantly higher in preeclamptic pregnancies compared to controls in the third trimester (difference of means = 16.8; 95% CI (9.0, 24.5); P < 0.001). There were no significant differences in placental stiffness between the two groups in the second trimester or between the severe preeclampsia and preeclampsia without severe features groups (difference of means = 9.86; 95% CI (−5.95, 25.7); P ≥ 0.05). Peripheral regions of the placenta were significantly stiffer than central regions in the preeclamptic group (difference of means = 10.67; 95% CI (0.07, 21.27); P < 0.05), which was not observed in the control group (difference of means = 0.55; 95% CI (−5.25, 6.35); P > 0.05). We did not identify a correlation of placental stiffness with gestational age, maternal age, gravidity or parity. However, there was a statistically significant correlation with BMI (P < 0.05). In addition, pregnancies with higher placental stiffness during the 2nd and 3rd trimesters had significantly reduced birth weight (2890 ± 176 vs. 2420 ± 219 g) and earlier GA (37.8 ± 0.84 vs. 34.3 ± 0.98 weeks) at delivery (P < 0.05). CONCLUSION: Compared to healthy pregnancies, placentas of preeclamptic pregnancies are stiffer and more heterogeneous. Placental stiffness is not affected by gestational age or the severity of preeclampsia but there is a correlation with higher BMI and poor perinatal outcomes.

Skin wounds heal by coordinated induction of inflammation and tissue repair, but the initiating events are poorly defined. Here we uncover a fundamental role of commensal skin microbiota in this process and show that it is mediated by the recruitment and the activation of type I interferon (IFN)-producing plasmacytoid DC (pDC). Commensal bacteria colonizing skin wounds trigger activation of neutrophils to express the chemokine CXCL10, which recruits pDC and acts as an antimicrobial protein to kill exposed microbiota, leading to the formation of CXCL10–bacterial DNA complexes. These complexes and not complexes with host-derived DNA activate pDC to produce type I IFNs, which accelerate wound closure by triggering skin inflammation and early T cell–independent wound repair responses, mediated by macrophages and fibroblasts that produce major growth factors required for healing. These findings identify a key function of commensal microbiota in driving a central innate wound healing response of the skin. Gilliet and colleagues demonstrate that skin wound healing occurs through the coordinated action of plasmacytoid dendritic cells, chemokines and skin microbiota.

Im Jahr 2016 hat die Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin (DGAI) und der Bund Deutscher Anasthesisten (BDA) 10 Qualitatsindikatoren (QI) veroffentlicht, um die Qualitat anasthesiologischer Behandlungen vergleichen und verbessern zu konnen. Bis heute gibt es keine Evidenz daruber, inwieweit sich die Masnahmen zur Implementierung der QI in den Kliniken umsetzen lassen. Im Rahmen dieser Studie wurde die Hypothese getestet, inwieweit die vorliegenden 10 QI in deutschen Krankenhausern implementierbar sind. Diese prospektive, dreiphasige, nationale, Multizenterstudie wurde in 15 deutschen Krankenhausern und einem ambulanten Anasthesie-Zentrum von Marz 2017 bis Februar 2018 durchgefuhrt. Die Studie bestand aus einer initialen Evaluation praexistierender Strukturen und Prozesse durch die Chefarzte der beteiligten Anasthesieabteilungen, gefolgt von einer sechsmonatigen Implementierungsphase der QI und einer finalen Reevaluation. Der Prozess der Implementierung wurde durch web-basierte Implementierungshilfen ( www.qi-an.org ) und interne Qualitatsmanagementprogramme der Zentren unterstutzt. Der primare Endpunkt war die Differenz der Anzahl implementierter QI pro Zentrum vor und nach der sechsmonatigen Implementierungsphase. Sekundare Endpunkte waren die Anzahl neu implementierter QI pro Zentrum, die Gesamtzahl erfolgreicher Implementierungen pro einzelnem QI, die Identifizierung von Problemen wahrend der Implementierung sowie die Grunde, die die Implementierung eines QI verhindert haben. Die durchschnittliche Anzahl implementierter QI pro Zentrum stieg von 5,8 auf 6,8 (Mittelwert der Differenzen 1,1 ± 1,3; p

Die Corona-Krise hat alle Mitgliedstaaten der Europäischen Union getroffen - allerdings einige früher und härter als andere. Nun soll ein immens großer Rettungsschirm aufgespannt werden, über dessen Finanzierung, Konditionen und mögliche Auflagen die EU-Mitglieder noch streiten. Auch die Ebenen, auf der die Maßnahmen organisiert werden sollen, sind noch nicht ausbalanciert. Welche Bedeutung kommt dabei der nationalen, welche der supranationalen Ebene zu? Geht es vor allem um die Europäische Währungsunion oder um die gesamte EU? Solidarisches Verhalten gebietet nicht allein die europäische Idee, sondern auch die ökonomische Notwendigkeit, da die Mitgliedstaaten über Lieferketten stark miteinander verflochten sind. The Coronavirus crisis has affected al of thel member states in the European Union - but some earlier and harder than others. A large rescue package is to be set up, the financing, conditions and possible requirements of which are still being disputed by EU members. The levels at which the measures are to be organised have not yet been established either. What is the importance of the national level or the supranational leves? Is it primarily about the European Monetary Union or about the EU as a whole? Solidarity is not only required by the European idea, but also by economic necessity, since the member states are strongly connected by their supply chains.

Derzeit gibt es verschiedene Materialien zur endovaskularen Behandlung von Aneurysmen. Die Wahl des Materials hangt dabei von der Lokalisation und Konfiguration des Aneurysmas ab. Um eine optimale Aneurysmabehandlung zu gewahrleisten, muss das Fullmaterial das Aneurysma inkorporieren und vom Tragergefas durch Ausbildung einer Endothelschicht und Neointimaproliferation entlang des Aneurysmahalses isolieren. Dadurch kann das Aneurysma dauerhaft vom Blutfluss isoliert und so die geschwachte Gefaswand langfristig stabilisiert werden, um eine nachfolgende Ruptur zu verhindern. Am haufigsten werden aktuell weiche Platinspiralen (Coils) verwendet. In den letzten Jahren wurden vermehrt Flussigembolisate zur endovaskularen Behandlung von Aneurysmen entwickelt. Einer der Grunde ist dabei, dass die injizierte Flussigkeit das Aneurysmalumen vollstandig ausfullt und somit unabhangig von der Aneurysmaform keine Lucke zwischen Fullmaterial und Aneurysmawand entsteht. Die meisten praklinischen und klinischen Studien liegen fur Onyx vor. Insbesondere zur Behandlung von mykotischen Aneurysmen sowie Aneurysmen der distalen hinteren Strombahn erweist sich die Flussigembolisation mit Onyx bereits als mogliche, effektive Behandlungsmethode.