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ZusammenfassungIn der vorliegenden Übersichtsarbeit diskutieren wir, wie iatrogene Blutverluste durch immunhämatologische Untersuchungen bei Früh- und Reifgeborenen minimiert werden können. Die Hauptursache für die Transfusion von Erythrozytenkonzentraten (EK) sind dabei iatrogene Blutverluste durch diagnostische Blutentnahmen. In einer Beobachtungsstudie betrug der iatrogene Blutverlust bei Frühgeborenen in den ersten 28 Lebenstagen im Median 24,2 mL/kg im Vergleich zum transfundierten EK-Volumen von 30 mL/kg im selben Zeitraum 1. Die Reduktion von diagnostischen Blutentnahmen stellt somit eine effiziente Maßnahme zur Reduzierung von EK-Transfusionen bei Frühgeborenen dar. Rationale und bedarfsadaptierte immunhämatologische Untersuchungen können den Blutverlust reduzieren, Transfusionen vermeiden und die entstehenden Kosten senken. Ferner stellen wir dar, wie durch differenzierte Auswahl von Blutkomponenten das Auftreten unerwünschter Ereignisse bei der Transfusion von Neugeborenen verhindert werden kann und regen an, restriktivere Indikationsstellungen zur Transfusion insbesondere in der Frühgeborenenmedizin zu diskutieren.

Objectives Osteoporotic vertebral compression fractures (OVCF) are a common increasing entity in elderly patients and represent a tremendous economic burden. Surgical treatment is related to high complication rates and little is known about patient-specific and internal risk factors associated with poor clinical results. Methods We carried out a comprehensive, systematic literature search according to the PRISMA checklist and algorithm. Risk factors for perioperative complications, for early inpatient readmission, for the duration of the hospital stay, the hospital mortality, the total mortality and the clinical result were analyzed. Results A total of 739 potentially usable studies were identified. After considering all inclusion and exclusion criteria, 15 studies with 15,515 patients were included. Non-adjustable risk factors were age >90 years (OR 3.27), male gender (OR 1.41), BMI less than 18.5 kg/m2 (OR 3.97), ASA score >3 (OR 2.7), activity of daily live (ADL) (OR 1.52), dependence (OR 5.68), inpatient admission status (OR 3.22), Parkinson disease (OR 3.63) and disseminated cancer (OR 2.98). Adjustable factors were insufficient kidney function (GFR Discussion We identified a couple of non-adjustable risk factors, which should be considered preoperatively in terms of risk assessment. However, even more important were adjustable factors that can be influenced preoperatively. In conclusion, we recommend a perioperative interdisciplinary cooperation, especially with geriatricians, to achieve the best possible clinical results in geriatric patients undergoing surgery for OVCF.

Study Design Systematic review. Objective The aim of this study was to conduct a systematic overview of the pathogenesis and the treatment options of combined odontoid and atlas fractures in geriatric patients. Methods This review is based on articles retrieved by a systematic search in the PubMed and Web of Science databases for articles published until February 2021 dealing with combination fractures of C1 and C2 in geriatric patients. Results Altogether, 438 articles were retrieved from the literature search. A total of 430 articles were excluded. The remaining eight original articles were included in this systematic review depicting the topics pathogenesis, non-operative treatment, posterior approach, and anterior approach. The overall level of evidence of the studies is low. Conclusion Combined odontoid and atlas fractures in the geriatric population are commonly caused by simple falls and seem to be associated with atlanto-odontoid osteoarthritis. Non-operative treatment with a cervical orthosis is a feasible treatment option in the majority of patients with stable C2 fractures. In case of surgery posterior C1 and C 2 stabilization and anterior triple or quadruple screw fixation are possible techniques. Some patients may also deserve an occipito-cervical fusion. A possible treatment algorithm is proposed.

Study Design Systematic review/expert consensus. Objectives Fractures of the axis represent the most frequent injury of the spine in elderly patients. Both, operative and non-operative treatment are associated with a high rate of complications and mortality. The aim of this article was to summarize the current literature on the management of odontoid fractures in geriatric patients and to weigh it based on an expert consensus process. Methods In a joint consensus process, members of the Spine Section of the German Orthopaedic and Trauma Society (DGOU) aimed to formulate recommendations for the diagnostic workup and treatment of odontoid fractures in geriatric patients. Based on the previously published recommendations, this article is an updated version with incorporating a systematic review of the recent literature. Results Based on the new data available, the recommendations established in the initial consensus process were adapted. Conclusions Computed tomography represents the diagnostic standard for patients with suspected injuries of the upper cervical spine. Anderson/D’Alonzo odontoid fractures type 1, non-displaced type 2, and type 3 can be treated conservatively. Even non-unions do not necessarily result in poor clinical outcome. In Anderson/D’Alonzo type 2 fractures, surgical therapy offers the advantage of relatively safe osseous healing with no increased complication rate even in elderly patients and can thus be recommended. In very high aged patients, however, a case-by-case decision should be made. When surgical stabilization of osteoporotic odontoid fractures is indicated, posterior techniques are biomechanically advantageous and can be considered the standard.

Assays in the coagulation laboratory are affected by numerous variables. Variables which have impact on the test result can lead to incorrect results, and potentially to consequences for further diagnostic and therapeutic decisions made by the clinician. The interferences can be separated into three main groups: biological interferences, with an actual impairment of the patient's coagulation system (congenital or acquired); physical interferences, which usually occur in the pre-analytical phase; and chemical interferences, because of the presence of drugs (mainly anticoagulants) in the blood to be tested. This article discusses some of these interferences in seven instructive cases of (near) miss events as an approach to generate more attention to these issues.

Purpose This study aimed to investigate the effect of epicutaneous vacuum therapy on the rate of unplanned spinal wound revisions compared with conventional wound dressing. Methods This retrospective study included patients who underwent unplanned revision spine surgery after primary aseptic spine surgery who were treated at a level I spine centre between December 2011 and December 2019. Patients with revision surgery who required a further unplanned revision surgery during the inpatient stay were considered a treatment failure. The epicutaneous vacuum-assisted closure (Epi-VAC) therapy was the standard treatment method beginning in 2017 (the epi-VAC group). Before, conventional wound dressing was used (the control group (CG)). In addition, a one-to-one matched-pair comparison analysis was performed between both groups. Results Of 218 patients, 48 were in the epi-VAC group. The mean age was 65.1 years (epi-VAC 68.2 to CG 64.3 years (P = 0.085)), and the mean body mass index (BMI) was 28.2 kg/m2 (epi-VAC 29.4 to CG 27.9 kg/m2 (P = 0.16)). No significant differences in the treatment failure rate could be detected between the two groups (epi-VAC 25% to CG 22.4% (P = 0.7)). There was also no significant difference for the matched-pair analysis (epi-VAC 26.1% to CG 15.2% (P = 0.3)). An elevated CRP level (C-reactive protein) immediately before the first wound revision was a significant risk factor for further revision surgery (treatment failure: 135.2 ± 128.6; no treatment failure: 79.7 ± 86.1 mg/l (P < 0.05)). Conclusion Concerning repeat unplanned wound revision after spinal revision surgery, we cannot demonstrate an advantage of the epicutaneous vacuum therapy over conventional wound dressing.

Lanthanide-doped upconversion nanoparticles (UCNPs) possess the remarkable ability to convert multiple near-infrared (NIR) photons into higher energy ultraviolet-visible (UV-vis) photons, making them a prime candidate for several advanced applications within the realm of nanotechnology. Compared to traditional organic fluorophores and quantum dots (QDs), UCNPs possess narrower emission bands (fwhm of 10-50 nm), large anti-Stokes shifts, low toxicity, high chemical stability, and resistance to photobleaching and blinking. In addition, unlike UV-vis excitation, NIR excitation is nondestructive at lower power intensities and has high tissue penetration depths (up to 2 mm) with low autofluorescence and scattering. Together, these properties make UCNPs exceedingly favored for advanced bioanalytical and theranostic applications, where these systems have been well-explored. UCNPs are also well-suited for bioimaging, optically modulating chemistries, forensic science, and other state-of-the-art research applications. In this review, an up-to-date account of emerging applications in UCNP research, beyond bioanalytical and theranostics, are presented including optogenetics, super-resolution imaging, encoded barcodes, fingerprinting, NIR vision, UCNP-assisted photochemical manipulations, optical tweezers, 3D printing, lasing, NIR-II imaging, UCNP-molecule nanohybrids, and UCNP-based persistent luminescent nanocrystals.

The title compound, 2,6-diamino-5-[(2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-yl)methyl]pyrimidin-1-ium methanesulfonate, C19H23N4O3 +·CH3O3S−, is a salt made up from a protonated iclaprim molecule and a mesylate anion. The pyrimidine and chromene units of the iclaprim molecule form an orthogonal arrangement [interplanar angle of 89.67 (6)°], and the 3-nitrogen position of the pyrimidine ring is protonated. Four distinct N—H...O interactions and an additional N—H...N hydrogen bond connect iclaprim and mesylate molecules to one another, resulting in an infinite hydrogen-bonded molecular tape structure. The central section of the tape is formed by a sequence of fused hydrogen-bonded rings involving four distinct ring types.

Background Light transmission aggregometry (LTA) is considered the gold standard for the evaluation of platelet function but is labor-intensive and involves numerous manual steps. Automation may contribute to standardization. Here, we evaluate the performance characteristics of a new automated instrument, Thrombomate XRA (TXRA), and compare it against a manual instrument (PAP-8). Materials and Methods Leftover blood samples from blood donors or patients were tested in parallel with identical reagents and in identical concentrations both manually using PAP-8 and automated on the TXRA. In addition to precision and method comparison, an additional evaluation was performed on the TXRA against “virtual” platelet-poor plasma (VPPP) based on artificial intelligence. The main focus was on comparing the maximum aggregation (MA%) values. Results Precision for MA% ranged from 1.4 to 4.6% on TXRA for all reagents. Normal ranges for 100 healthy blood donors on both instruments were in a similar range for all reagents, with a tendency to slightly higher values with TXRA. Most agonists resulted in normally distributed MA%. Comparing 47 patient samples on both devices showed a good correlation for both slope and MA% with some differences in individual samples with epinephrine and TRAP. Correlation between the TXRA measurement against PPP and “virtual” PPP demonstrated excellent correlation. Reaction signatures of both devices were very similar. Conclusion TXRA provides reproducible LTA results that correlate with an established manual method when tested against PPP or VPPP. Its ability to perform LTA only from platelet-rich plasma without requiring autologous PPP simplifies LTA. TXRA is an important step not only for further standardizing LTA but also for a more widespread use of this important method.

Vacuum glazing products have been in development for the past decades. Such glazing products regularly feature two parallel glass panes that have a small, evacuated gap in their interstitial space. To maintain the vacuum and the form of the glass product, regularly vacuum tight edge seals and a grid of distance pillars are integrated. During the years of development, the major focus was set on the production and durability aspects of the glass products, but relatively few efforts had been conducted towards the integration of such glass products into window constructions. Employing typically used double- and triple glazing windows’ frames does not represent a feasible option. This is due to the specification given by vacuum glazing products, such as their small thickness and the requirement for sufficient glass edge coverage due to the major thermal bridge adjacent to the edge seal.The authors, together with major players from the window producing industry, started a R&D effort that targeted disruptive new concepts for vacuum glass windows. Four different designs were developed that not only integrated vacuum glass products, but also featured unusual opening patterns, the latest generation of electrically driven fitting products, and specific seals. The thermal and acoustical performance of the prototypes was improved during the development via employment of numeric thermal simulation and lab testing. The present contribution illustrates the four prototypes and their performance, which – for instance – pertaining to the UW-value is down to 0.6–0.7 W · m−2 · K−1 at a glass thickness of less than 1 cm.

Blood coagulation analysis is characterized by the application of a variety of materials, reagents, and analyzers for the determination of the same parameter, or analyte, by different laboratories worldwide. Accordingly, the application of common reference intervals, that, by definition, would represent a "range of values (of a certain analyte) that is deemed normal for a physiological measurement in healthy persons," is difficult to implement without harmonization of procedures. In fact, assay-specific reference intervals are usually established to allow for the discrimination of normal and abnormal values during evaluation of patient results. While such assay-specific reference intervals are often determined by assay manufacturers and subsequently adopted by customer laboratories, verification of transferred values is still mandatory to confirm applicability on site. The same is true for reference intervals that have been adopted from other laboratories, published information, or determined by indirect data mining approaches. In case transferable reference intervals are not available for a specific assay, a direct recruiting approach may or needs to be applied. In comparison to transferred reference interval verification, however, the direct recruiting approach requires a significantly higher number of well-defined samples to be collected and analyzed. In the present review, we aim to give an overview on the above-mentioned aspects and procedures, also with respect to relevant standards, regulations, guidelines, but also challenges for both, assay manufacturers and coagulation laboratories.Die Gerinnungsdiagnostik ist durch die Anwendung verschiedenster Reagenzien und Assays zur Bestimmung einzelner Analyten gekennzeichnet. Dementsprechend bedarf die Anwendung übergreifender, generischer Referenzintervalle, die per Definition einen “Wertebereich (eines bestimmten Analyten), der für eine physiologische Messung bei gesunden Personen als normal angesehen wird,” darstellen würden, einer entsprechenden Harmonisierung von Testverfahren. Somit werden in der Regel Assay-spezifische Referenzintervalle festgelegt, um eine Unterscheidung zwischen normalen und abnormalen Messwerten im Rahmen der Analyse von Patientenproben zu ermöglichen. Während entsprechende Referenzintervalle häufig von den Testherstellern ermittelt und anschließend von den anwendenden Laboren übernommen werden, bleibt eine Verifizierung der übertragenen Werte obligatorisch, um deren Anwendbarkeit vor Ort zu bestätigen. Das gleiche gilt für Referenzintervalle, die aus Veröffentlichungen oder von anderen Labors übernommen, oder aber durch indirekte (Data-Mining) Verfahren ermittelt wurden. Falls für einen bestimmten Assay keine übertragbaren Referenzintervalle verfügbar sind, kann (oder muss) ein direktes Rekrutierungsverfahren angewandt werden. Im Vergleich zur Verifizierung von übertragenen Referenzintervallen erfordert dieser direkte Ansatz jedoch eine wesentlich höhere Anzahl an zu analysierenden Proben gesunder Probanden. In der hier vorliegenden Arbeit soll ein Überblick über die vorgenannten Aspekte und Verfahren der Erhebung von Referenzintervallen geben werden. Dies auch im Hinblick auf einschlägige Normen, Vorschriften und Richtlinien, aber auch bezüglich der hiermit verbundenen Herausforderungen sowohl für Hersteller als auch Labore.

Thrombophilia leads to an increased risk of venous thromboembolism. Widely accepted risk factors for thrombophilia comprise deficiencies of protein C, protein S, and antithrombin, as well as the factor V "Leiden" mutation, the prothrombin G20210A mutation, dysfibrinogenemia, and, albeit less conclusive, increased levels of factor VIII. Besides these established markers of thrombophilia, risk factors of unclear significance have been described in the literature. These inherited risk factors include deficiencies or loss-of-activity of the activity of ADAMTS13, heparin cofactor II, plasminogen, tissue factor pathway inhibitor (TFPI), thrombomodulin, protein Z (PZ), as well as PZ-dependent protease inhibitor. On the other hand, thrombophilia has been linked to the gain-of-activity, or elevated levels, of α2-antiplasmin, angiotensin-converting enzyme, coagulation factors IX (FIX) and XI (FXI), fibrinogen, homocysteine, lipoprotein(a), plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI). With respect to the molecular interactions that may influence the thrombotic risk, more complex mechanisms have been described for endothelial protein C receptor (EPCR) and factor XIII (FXIII) Val34Leu. With focus on the risk for venous thrombosis, the present review aims to give an overview on the current knowledge on the significance of the aforementioned markers for thrombophilia screening. According to the current knowledge, there appears to be weak evidence for a potential impact of EPCR, FIX, FXI, FXIII Val34Leu, fibrinogen, homocysteine, PAI-1, PZ, TAFI, and TFPI on the thrombotic risk.Eine Thrombophilie führt zu einem erhöhten Risiko für venöse thromboembolische Ereignisse. Weithin anerkannte Risikofaktoren für eine Thrombophilie sind ein Mangel an Protein C, Protein S und Antithrombin, sowie die Faktor-V-“Leiden”-Mutation, die Prothrombin-G20210A-Mutation, eine Dysfibrinogenämie und, weniger eindeutig, erhöhte Faktor VIII-Aktivitäten. Neben diesen etablierten Markern sind in der Literatur auch Risikofaktoren von eher unklarem Stellenwert beschrieben. Zu diesen Risikofaktoren, bzw. Markern, gehören der Funktionsverlust (loss-of-activity), bzw. der Mangel, der Aktivität von ADAMTS13, Heparin-Cofaktor II (HCII), Plasminogen, Tissue Factor Pathway Inhibitor (TFPI), Thrombomodulin (TM), Protein Z (PZ) sowie des Protein Z-abhängigen Proteaseinhibitors (ZPI). Andererseits wurde eine Thrombophilie mit einem gain-of-activity, bzw. erhöhten Aktivitäten, von α2-Antiplasmin (a2-AP), Angiotensin-konvertierendem Enzym (ACE), den Gerinnungsfaktoren IX (FIX) und XI (FXI), Fibrinogen, Homocystein, Lipoprotein(a), Plasminogenaktivator-Inhibitor-1 (PAI-1) sowie dem Thrombin-aktivierbaren Fibrinolyse-Inhibitor (TAFI) in Verbindung gebracht. Im Hinblick auf die zugrundeliegenden molekularen Interaktionen, die einen Einfluss auf das Thromboserisiko haben könnten, stellen sich die Mechanismen für den endothelialen Protein-C-Rezeptor (EPCR) und den Faktor-XIII-(FXIII) Val34Leu komplexer dar. In der vorliegenden Arbeit soll ein Überblick über den aktuellen Wissensstand zur Bedeutung dieser Marker für das Thrombophilie-Screening bei Patienten mit venösen thromboembolischen Ereignissen gegeben werden. Hierbei zeigt sich nach derzeitigem Kenntnisstand eine schwache Evidenz für einen möglichen Einfluss von EPCR, F IX, F XI, F XIII Val34Leu, Fibrinogen, Homocystein, PAI-1, PZ, TAFI und TFPI auf das Thromboserisiko.

Achieving long-term (3 months) colloidal stability of upconversion nanoparticles (UCNPs) in biologically relevant buffers has been a major challenge, which has severely limited practical implementation of UCNPs in bioimaging and nanomedicine applications. To address this challenge, nine unique copolymers formulations were prepared and evaluated as UCNP overcoatings. These polymers consisted of a poly(isobutylene

Purpose/Objective Multiple tumorous lesions in one pituitary gland are rare and mostly described in case reports. Their incidences and combinations are defined in larger collectives. Therefore, we analyzed our large collection for double tumors and combinations of tumors, cysts, and inflammation. Methods The German Registry of Pituitary Tumors, including cases from 1990 to 2018, served as the database. Our collection comprises a total of 16,283 cases up until the end of 2018. Of these cases, 12,673 originated from surgical and 3,610 from autopsy material. All specimens were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin–eosin and PAS. Monoclonal (prolactin, TSH, FSH, LH, and α subunit) or polyclonal (GH and ACTH) antibodies were used to detect pituitary hormones in the lesions. Since 2017, antibodies against the transcription factors Pit-1, T-Pit, and SF-1 have been used in difficult cases. The criteria of the 2017 WHO classification have been basic principles for classification since 2018 (Osamura et al. 2017). For differentiation of other sellar tumors, such as meningiomas, chordomas, or metastases, the use of additional antibodies was necessary. For these cases, it was possible to use a broad antibody spectrum. Autopsy pituitaries were generally studied by H&E and PAS sections. If any lesions were demonstrated in these specimens, additional immunostaining was performed. Results Multiple tumorous lesions with more than one pituitary neuroendocrine tumor (PitNET) respectively adenoma make up 1.4% (232 cases) in our collection. Within the selected cases, synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17.3%, PANCH cases (pituitary adenoma with neuronal choristoma) for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2%, and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years, with a standard deviation of 18.5 years. A total of 55.3% of the patients were female and 44.7% were male. From 1990 to 2018, there was a continuous increase in the number of multiple tumorous lesions. Conclusion From our studies, we conclude that considering possible tumorous double lesions during surgeries and in preoperative X-ray analyses is recommended.

Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed.Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed.A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness.Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients.Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments.

Observing proteins as they perform their tasks has largely remained elusive, which has left our understanding of protein function fundamentally incomplete. To enable such observations, we have recently proposed a novel technique that improves the time resolution of cryo-electron microscopy (cryo EM) to microseconds. Here, we demonstrate that microsecond time-resolved cryo-EM enables observations of fast protein dynamics. We use our approach to elucidate the mechanics of the capsid of cowpea chlorotic mottle virus (CCMV), whose large-amplitude motions play a crucial role in the viral life cycle. We observe that a pH jump causes the extended configuration of the capsid to contract on the microsecond timescale. While this is a concerted process, the motions of the capsid proteins involve different timescales, leading to a curved reaction path.

Humoral anti-platelet factors such as autoantibodies are thought to primarily clear platelets by triggering macrophage phagocytosis in immune thrombocytopenia (ITP). However, there are scarce studies characterizing the capacity and mechanisms of humoral factor-triggered macrophage phagocytosis of platelets using ITP patient specimens. Here, we assessed sera from a cohort of 24 ITP patients for the capacity to trigger macrophage phagocytosis of normal donor platelets and characterized the contribution of humoral factors to phagocytosis. Sera that produced a phagocytosis magnitude greater than a normal human serum mean plus two standard deviations were considered phagocytosis positive. Overall, 42% of ITP sera were phagocytosis positive. The indirect monoclonal antibody immobilization of platelet antigens assay was used to detect IgG autoantibodies to GPIIb/IIIa, GPIb/IX, and GPIa/IIa. Autoantibody positive sera triggered a higher mean magnitude of phagocytosis than negative sera. Phagocytosis correlated inversely with platelet counts among autoantibody positive patients but not autoantibody negative patients. Select phagocytosis positive sera were separated into IgG purified and depleted fractions via protein G and reassessed for phagocytosis. Phagocytosis was largely retained in the purified IgG fractions. Additionally, we assessed serum concentrations of C-reactive protein, serum amyloid P, and pentraxin 3 as potential phagocytosis modulators. Pentraxin 3 concentrations correlated inversely with platelet counts among patients positive for autoantibodies. Taken together, approximately half of the ITP patient sera studied triggered macrophage phagocytosis of platelets beyond a normal level. An important role for anti-platelet autoantibodies in phagocytosis is supported; a role for pentraxins such as pentraxin 3 may be suggested.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany.

Study DesignMulticenter prospective cohort study.ObjectiveThe study aims to validate the recently developed OF score for treatment decisions in patients with osteoporotic vertebral compression fractures (OVCF).MethodsThis is a prospective multicenter cohort study (EOFTT) in 17 spine centers. All consecutive patients with OVCF were included. The decision for conservative or surgical therapy was made by the treating physician independent of the OF score recommendation. Final decisions were compared to the recommendations given by the OF score. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5 L, and Barthel Index.ResultsIn total, 518 patients (75.3% female, age 75 ± 10) years were included. 344 (66%) patients received surgical treatment. 71% of patients were treated following the score recommendations. For an OF score cut-off value of 6.5, the sensitivity and specificity to predict actual treatment were 60% and 68% (AUC .684, P < .001). During hospitalization overall 76 (14.7%) complications occurred. The mean follow-up rate and time were 92% and 5 ± 3.5 months, respectively. While all patients in the study cohort improved in clinical outcome parameters, the effect size was significantly less in the patients not treated in line with the OF score’s recommendation. Eight (3%) patients needed revision surgery.ConclusionsPatients treated according to the OF score’s recommendations showed favorable short-term clinical results. Noncompliance with the score resulted in more pain and impaired functional outcome and quality of life. The OF score is a reliable and save tool to aid treatment decision in OVCF.

Major improvements in outcome of older patients with multiple myeloma (MM) have been achieved with the introduction of novel agents. Their impact in real-life treatment of older patients is unclear. In this single center retrospective study, we analyzed the outcome of patients65 years treated with first-generation (FGNA) and second-generation novel agents (SGNA) within two time periods 2012-2014 and 2015-2017. Patients were analyzed based on age, Charlson Comorbidity Index (CCI), International Staging System stage, year of diagnosis and withdrawal of agents due to toxicities. Overall 96 patients were included for analysis. Median age was 73 years (range 65-90), 55 (57%) patients were 65-75 years and 41 (43%) were75 years old. 84 patients received a first-line therapy, whereas 45 patients had ≥2 lines of systemic therapy. 20 patients were consolidated with autologous stem cell transplantation. 12 patients had no systemic therapy at all. In 17 of 21 cases a FGNA and in 4 of 21 a SGNA was withdrawn due to toxicity. Median overall survival (OS) for all patients with systemic therapy was 4.75 years (95% CI, 3.05-NA). Borderline significant improvement of OS was observed in patients diagnosed 2015-2017 compared to 2012-2014 with HR 0.57 (95% CI, 0.31-1.02) p = 0.06. OS significantly differed for comorbid patients with low and intermediate risk CCI, HR 1.94 (95% CI, 1.07-3.54), p = 0.03 in the overall population. OS in patients treated with SGNA was not significantly different in patients with intermediate versus low risk CCI (HR 1.48 (95% CI 0.43-5.14, p = 0.54)). In conclusion, we found a trend toward improved survival for older MM patients after the introduction of novel agents during the observed time period. In patients treated with SGNA a smaller effect that comorbidity negatively affects survival was observed.

Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti-human platelet antigen-1a antibodies (anti-HPA-1a). Anti-HPA-5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti-HPA-5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental. This review of the literature related to FNAIT using the MEDLINE database was conducted according to PRISMA guidelines. A retrospective analysis of a single-centre cohort of 817 suspected FNAIT cases was conducted. The pooled prevalence of anti-HPA-5b antibodies in unselected pregnant women of European descent was 1.96% (n = 3113), compared with 3.4% (n = 5003) in women with suspected FNAIT. We found weak evidence that a small proportion of pregnant women presenting with anti-HPA-5b antibodies will give birth to a newborn with mild thrombocytopenia. The neonatal platelet counts were not different between suspected FNAIT cases (n = 817) with and without maternal anti-HPA-5b antibodies. The prevalence of maternal anti-HPA-5b antibodies was not different between neonates with intracranial haemorrhage and healthy controls. The current experimental and epidemiological evidence does not support the hypothesis that anti-HPA-5b antibodies cause severe thrombocytopenia or bleeding complications in the fetus or newborn.

The hybrid zero dynamics control concept for bipedal walking is extended to include a non-instantaneous double support phase. A symmetric robot that consists of five rigid body segments which are connected by four actuated revolute joints is considered. Periodic walking gaits with a constant average walking speed consists of alternating single (SSP) and double support phases (DSP). Hybrid zero dynamics control designs usually assume an instantaneous DSP, which is a severe limitation. The proposed controllers use continuous SSPs and DSPs. Transitions between both phases are modeled as instantaneous events, when the rear leg lifts off at the end of the DSP and the swing leg touches down at the end of the SSP. Due to the fact that the model during the DSP has more actuators (4) than degrees of freedom (3), the system is overactuated. In order to combine it with the underactuated SSP model and then formulate a periodic walking gait, we suggest three controller designs for different applications. One with the underactuated DSP, one with the fully actuated DSP, and one with the overactuated DSP. A numerical optimization is used to generate energy efficient gaits in an offline process. According to the optimization results, artificially creating an underactuated controller for the DSP results in the most efficient gaits. Adding control tasks utilizing the full actuation or overactuation during the DSP significantly improves the gait stability., 36 pages, 13 figures

We have recently introduced a microsecond time-resolved version of cryo-electron microscopy (cryo-EM) to enable the observation of the fast conformational motions of proteins. Our technique involves locally melting a cryo sample with a laser beam to allow the proteins to undergo dynamics in liquid phase. When the laser is switched off, the sample cools within just a few microseconds and revitrifies, trapping particles in their transient configurations, in which they can subsequently be imaged. We have previously described two alternative implementations of the technique, using either an optical microscope or performing revitrification experimentsin situ. Here, we show that it is possible to obtain near-atomic resolution reconstructions fromin siturevitrified cryo samples. Moreover, the resulting map is indistinguishable from that obtained from a conventional sample within our spatial resolution. Interestingly, we observe that revitrification leads to a more homogeneous angular distribution of the particles, suggesting that revitrification may potentially be used to overcome issues of preferred particle orientation.SynopsisNear-atomic resolution reconstructions can be obtained fromin situmelted and revitrified cryo samples. Revitrification results in a more homogeneous angular distribution.

no Abstract

"In Deutschland...(kann) jeder so sprechen und schreiben..., wie er verstanden...werden will", erklärte der Vorsitz der Gesellschaft für deutsche Sprache. 1: Dieser Grundsatz ist anwendbar auf den "gerechten" Wortgebrauch in Studium und Berufslehre, weniger auf den Spracherwerb in der Schule. 2: Der Redefreiheit wegen, jedoch bei Klarheit des Ausdrucks. Er ist zu ergänzen um die Machtfrage im rechtlichen Rahmen: Persönlichkeitsrecht, amtlicher Rechtschrieb, Lehrfreiheit und institutionelle Autonomie.

Background In older multimorbid orthopedic and rheumatic patients, data on symptoms besides pain or reduced mobility are rarely published. Objective We investigated patients’ perspectives on their symptoms after hospital discharge. Material and methods Orthopedic and rheumatic patients aged over 70 years were asked via telephone interviews about (i) their symptoms, (ii) communication, (iii) treatment, and (iv) support. Results (i) The 60 participants (35 women and 25 men) reported a median of 6 (min-max: 1–14) different symptoms, of which 86% (356 of 415) had existed before hospitalization, (ii) patients did not communicate 28% (117) of symptoms to either healthcare professionals, family or friends and (iii) 52 (87%) patients desired improvement. Of the 280 most impairing symptoms, 19% (52) were not treated at all. (iv) Almost all patients (59; 98%) considered it easy to obtain support. Conclusion Remarkably, many symptoms were not communicated or treated despite the patients having been hospitalized.

In recent years, Berlin and its surrounding area has experienced multiple intensive precipitation events, which caused significant damage and severely impaired the local infrastructure. An extreme value analysis of the available station data could improve the understanding of such events and provide valuable information for risk assessments in the region. Additionally, results gathered from this analysis will serve as a reference for similar evaluations with the Central European Refined analysis (CER), a gridded dataset generated via dynamical downscaling of ERA5 data using the Weather Research and Forecasting model. In this study, we assess the spatiotemporal dynamics of extreme precipitation event days in Berlin and Brandenburg using a generalized Pareto distribution (GPD). Daily precipitation data of the last 30 years was extracted at 137 stations of the German Meteorological Service. The GPD at each station was fitted using a peak over threshold approach with a seasonal time-dependent threshold and scale parameter. For the resulting distribution, 2-, 10-, and 20-year return levels were calculated for each season. 20-year precipitation extremes showed a high regional variability with slightly higher values around Berlin reaching up to 130 mm d-1 in the summer. Return levels also tended to be higher in the northern parts of Berlin and Brandenburg during winter and in the south during spring., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Light transmission aggregation (LTA) is used widely by the clinical and research communities. While it is a gold standard, there is a lack of inter-laboratory harmonization. The primary objective was to assess whether sources of activators (mainly Adenosine diphosphate (ADP), Collagen, Arachidonic acid, Epinephrine, Thrombin Receptor Activating Peptide (TRAP)6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathological results. International multi-center study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator which we supplied. We report a variability in the potency (P) of activators in comparison to the comparator. TRAP6 (P:1.32-2.68), arachidonic acid (P:0.87-1.43) and epinephrine (P:0.97-1.34) showed the greatest variability. ADP (P:1.04-1.20) and ristocetin (P:0.98-1.07) were the most consistent. The data highlighted clear interindividual variability notably for ADP and epinephrine. Four profiles of response were observed with ADP from high responders, intermediate responders and low responders. A fifth profile corresponding to non-responders (5% of the individuals) was observed with epinephrine. On the basis of these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.

In a field experiment with 341 participants, we study whether social comparisons, either in isolation or in combination with a climate-related moral appeal, can change the use of public and car-related transportation. We do so in the context of a mobility budget offered to employees of a large German company as an alternative to a company car. The budget can be used to pay for both leisure and commuting trips, and for various modes of transport. Behavioral interventions in this setting are of particular interest, since companies are constrained to significantly alter financial benefits to employees yet strive to lower carbon emissions via a shift to low-emission transport modes. We find strong evidence for a reduction in car-related mobility in response to the combined treatment, driven by reduced expenditures for taxi and UBER rides. This is accompanied by substitution towards micromobility, but not towards public transport. Furthermore, we do not find any effects of the social comparison alone. Our results demonstrate that norm-based nudges are able to change transportation behavior, at least temporarily.

International audience; The Se77(n,γ) reaction is of importance for Se77 abundance during the slow neutron capture process in massive stars. We have performed a new measurement of the Se77 radiative neutron capture cross section at the Neutron Time-of-Flight facility at CERN. Resonance capture kernels were derived up to 51 keV and cross sections up to 200 keV. Maxwellian-averaged cross sections were calculated for stellar temperatures between kT=5keV and kT=100keV, with uncertainties between 4.2% and 5.7%. Our results lead to substantial decreases of 14% and 19% in Se77 abundances produced through the slow neutron capture process in selected stellar models of 15M⊙ and 2M⊙, respectively, compared to using previous recommendation of the cross section.

Supplemental Material for Spinal Orthoses in the Treatment of Osteoporotic Thoracolumbar Vertebral Fractures in the Elderly: A Systematic Review With Quantitative Quality Assessment by Philipp Pieroh, Ulrich J.A. Spiegl, Anna Völker, Sven Märdian, Nicolas H. von der Höh, Georg Osterhoff, Christoph-E. Heyde; Spine Section of the German Society for Orthopaedics and Trauma in Global Spine Journal

Climate change is perhaps the biggest challenge of our times. In order to cope with it, we have to organise action collectively. The most important way to cooperate globally is through United Nations negotiations, known as ‘conferences of the parties’. However, progress has been very slow, and disillusionment with the United Nations Framework Convention on Climate Change process has set in. From a scientific point of view, several obstacles surfacing in these negotiations have been well researched. Institutional analysis may provide suggestions or even solutions to some of these problems. Hence, we think that the United Nations Framework Convention on Climate Change negotiations could profit from scientific support. We provide scientific background for three prominent problems: how to reconcile different interests in a global public goods situation; how to ameliorate the consensus decision-making process; and how to design institutions to implement resolutions. Enhancing communication, trust and fairness, and enforcing sanctions, are suggested as key elements for that. Finally, we point to similar processes that have been brought to a successful end.

Introduction Procedures like kyphoplasty or vertebroplasty have become an established treatment option for vertebral compression fractures (VCF). The transpedicular approach used during these procedures allows to take biopsies from the affected vertebral body. The aim of this study was to systematically summarize the existing knowledge on the value of routine transpedicular biopsies during kyphoplasty or vertebroplasty for vertebral compression fractures. Methods A systematic review of the literature using PubMed/Medline databases with the goal of finding all articles describing the value trans-pedicular biopsies for detecting primary bone tumors, metastases, bone diseases, or spondylitis in patients with vertebral compression fractures was performed. Search terms were (*biopsy/ OR biops*.ti,ab.) AND (vertebral compression fracture*.ti,ab.). Results Sixteen articles met the inclusion criteria, among these were six prospective and ten retrospective case series. Publication dates ranged from 2005 to 2020. A total of 3083 patients with 3667 transpedicular biopsies performed were included. Most biopsies confirmed osteoporosis as the dominant underlying pathology of VCFs. Transpedicular biopsies revealed an unexpected malignant diagnosis in 0.4–6% of the cases. Conclusion Routine transpedicular biopsies during kyphoplasty or vertebroplasty detect unexpected malignant lesions in 0.4–6% of the patients, even though the definition of “unexpected” varies among the analyzed studies. The evidence to support a routine biopsy is inconsistent. Nevertheless, routine biopsies can be considered, especially when sufficient preoperatvie imaging is not available or radiological findings are unclear.

Two bipyridine isomers (2,2′- and 4,4′-), used as coformers and ligands in coordination chemistry, were subjected to solid form screening and crystal structure prediction. One anhydrate and a formic acid disolvate were crystallized for 2,2′-bipyridine, whereas multiple solid-state forms, anhydrate, dihydrate, and eight solvates with carboxylic acids, including a polymorphic acetic acid disolvate, were found for the 4,4′-isomer. Seven of the solvates are reported for the first time, and structural information is provided for six of the new solvates. All twelve solid-state forms were investigated comprehensively using experimental [thermal analysis, isothermal calorimetry, X-ray diffraction, gravimetric moisture (de)sorption, and IR spectroscopy] and computational approaches. Lattice and interaction energy calculations confirmed the thermodynamic driving force for disolvate formation, mediated by the absence of H-bond donor groups of the host molecules. The exposed location of the N atoms in 4,4′-bipyridine facilitates the accommodation of bigger carboxylic acids and leads to higher conformational flexibility compared to 2,2′-bipyridine. For the 4,4′-bipyridine anhydrate ↔ hydrate interconversion hardly any hysteresis and a fast transformation kinetics are observed, with the critical relative humidity being at 35% at room temperature. The computed anhydrate crystal energy landscapes have the 2,2′-bipyridine as the lowest energy structure and the 4,4′-bipyridine among the low-energy structures and suggest a different crystallization behavior of the two compounds., The solid form landscapes of 2,2′- and 4,4′-bipyridine were explored experimentally and computationally. The position of the nitrogen atoms defines not only the conformational flexibility of the molecule but also the crystallization behavior. 4.4′-Bipyridine was found to be more prone to solvate (including hydrate) formation than its 2,2′-isomer.

Objectives Osteoporotic fractures of the pelvis (OFP) are an increasing issue in orthopedics. Current classification systems (CS) are mostly CT-based and complex and offer only moderate to substantial inter-rater reliability (interRR) and intra-rater reliability (intraRR). MRI is thus gaining importance as a complement. This study aimed to develop a simple and reliable CT- and MRI-based CS for OFP. Methods A structured iterative procedure was conducted to reach a consensus among German-speaking spinal and pelvic trauma experts over 5 years. As a result, the proposed OF-Pelvis CS was developed. To assess its reliability, 28 experienced trauma and orthopedic surgeons categorized 25 anonymized cases using X-ray, CT, and MRI scans twice via online surveys. A period of 4 weeks separated the completion of the first from the second survey, and the cases were presented in an altered order. While 13 of the raters were also involved in developing the CS (developing raters (DR)), 15 user raters (UR) were not deeply involved in the development process. To assess the interRR of the OF-Pelvis categories, Fleiss’ kappa (κF) was calculated for each survey. The intraRR for both surveys was calculated for each rater using Kendall’s tau (τK). The presence of a modifier was calculated with κF for interRR and Cohen’s kappa (κC) for intraRR. Results The OF-Pelvis consists of five subgroups and three modifiers. Instability increases from subgroups 1 (OF1) to 5 (OF5) and by a given modifier. The three modifiers can be assigned alone or in combination. In both surveys, the interRR for subgroups was substantial: κF = 0.764 (Survey 1) and κF = 0.790 (Survey 2). The interRR of the DR and UR was nearly on par (κF Survey 1/Survey 2: DR 0.776/0.813; UR 0.748/0.766). The agreement for each of the five subgroups was also strong (κF min.–max. Survey 1/Survey 2: 0.708–0.827/0.747–0.852). The existence of at least one modifier was rated with substantial agreement (κF Survey 1/Survey 2: 0.646/0.629). The intraRR for subgroups showed almost perfect agreement (τK = 0.894, DR: τK = 0.901, UR: τK = 0.889). The modifier had an intraRR of κC = 0.684 (DR: κC = 0.723, UR: κC = 0.651), which is also considered substantial. Conclusion The OF-Pelvis is a reliable tool to categorize OFP with substantial interRR and almost perfect intraRR. The similar reliabilities between experienced DRs and URs demonstrate that the training status of the user is not important. However, it may be a reliable basis for an indication of the treatment score.

To assess the potential influence of multifidus atrophy and fatty degeneration on the incidence of adjacent vertebral compression fractures within one year after the index fracture. In a retrospective cohort study, patients who underwent surgery for an OVCF were identified and baseline characteristics, fracture patterns and the occurrence of secondary adjacent fractures within one year were obtained by chart review. Multifidus muscle atrophy and fatty degeneration were determined on preoperative MRI or CT scans. In this analysis of 191 patients (mean age 77 years, SD 8, 116 female), OF type 3 was the most common type of OVCF (49.2%). Symptomatic adjacent OVCFs within one year after index fracture were observed in 23/191 patients (12%) at mean 12, SD 12 weeks (range 1–42 weeks) postoperatively. The mean multifidus muscle area was 264, SD 53 mm2 in patients with an adjacent vertebral fracture and 271, SD 92 mm2 in patients without a secondary fracture (p = 0.755). Mean multifidus fatty infiltration was graded Goutallier 2.2, SD 0.6 in patients with an adjacent fracture and Goutallier 2.2, SD 0.7 in patients without an adjacent fracture (p = 0.694). Pre-existing medication with corticosteroids was associated with the occurrence of an adjacent fracture (p = 0.006). Multifidus area and multifidus fatty infiltration had no significant effect on the occurrence of adjacent vertebral fractures within one year after the index fracture. Patients with a pre-existing medication with corticosteroids were more likely to sustain an adjacent fracture.

not abstract, please contact Dr. Hentzelt, Publication manager Karger.

How people cooperate to provide public goods is an important scientific question and relates to many societal problems. Previous research studied how people cooperate in stable groups in repeated or one-time-only encounters. However, most real-world public good problems occur in groups with a gradually changing composition due to old members leaving and new members arriving. How group changes are related to cooperation in public good provision is not well understood. To address this issue, we analyze a dataset from an online public goods game comprising approximately 1.5 million contribution decisions made by about 135 thousand players in about 11.3 thousand groups with about 234 thousand changes in group composition. We find that changes in group composition negatively relate to cooperation. Our results suggest that this is related to individuals contributing less in the role of newcomers than in the role of incumbents. During the process of moving from newcomer status to incumbent status, individuals cooperate more and more in line with incumbents.