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Background Shoulder pathology can occur concurrently with a distal radius fracture (DRF) but few studies have examined this population. Purpose The purpose of this study was to expand the understanding of the impact of shoulder pathology on individuals with DRF. Study Design: Mixed Methods Design. Methods A total of 45 participants with a DRF were categorized into a DRF only (n = 29) and shoulder pathology concurrent with DRF (SPCDRF) (n = 16) groups. Quantitative data gathered included demographics, Quick Disabilities of the Arm, Shoulder, and Hand, Tampa Scale of Kinesiophobia-11, Visual Analog Scale, and Compensatory Mechanism Checklist. Qualitative interviews were performed with 7 participants in the SPCDRF group. Within group correlations were analyzed via the Spearman Rank. The Mann Whitney U test was used to compare the two groups. Qualitative analysis was performed to describe the experience of participants in the SPCDRF group. A mixed methods analysis compared quantitative and qualitative data. Results Sixteen participants (35.6%) in the sample presented with shoulder pathology; 6 participants (37.5%) presented at initial evaluation due to the fall; 10 participants (62.5%) developed shoulder pathology due to compensation or disuse. Average number of days to develop shoulder pathology after the DRF was 43 days. SPCDRF participants had significantly greater pain levels (p = .02) and more activity avoidance (p = .03) than the DRF only group. Four qualitative themes emerged: It's difficult to perform occupations and changes had to be made; There is fear and uncertainty; The impact of pain; Tried to be normal but could not Mixed methods analysis found that qualitative data further illuminated quantitative findings. Conclusions Individuals with shoulder pathology concurrent with a DRF may present with higher pain levels and avoid activity more. In addition, they may describe fearfulness in using their injured upper extremity especially if they have high levels of pain. Study Design Mixed Methods Design.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

OBJECTIVE Women veterans are disproportionately affected by intimate partner violence (IPV). Within the civilian literature, intimate partner stalking (IPS) is a common, uniquely deleterious form of IPV; the present study seeks to prospectively examine the psychological effects of IPS among women veterans. METHOD Women veterans (n = 266) were recruited using the KnowledgePanel, a probability-based survey panel; participants completed surveys at time 1 (T1) and at time 2 (T2) follow-up 18 months later. Women responded to questionnaires assessing IPV and IPS experiences, and symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. RESULTS At T1, 54.5% of women reported lifetime IPV, of whom 64.1% reported IPS; at T2, 49.2% reported past-year IPV, of whom 7.6% experienced past-year IPS. Bivariately, women in the T1 IPS group reported higher T2 PTSD, depression, and anxiety symptoms than the T1 IPV only and no IPV groups. In a multivariate model, there remained indirect effects of T1 IPS on T2 PTSD symptoms, when other forms of violence (i.e., T1 and T2 IPV, MST, IPS) were controlled. CONCLUSIONS When added to models including other forms of IPV, women who experienced IPS reported increased risk for PTSD symptoms, which predicted heightened PTSD symptoms over time. Providers treating women veterans should assess for experiences of IPS as an additional form of IPV and address PTSD to prevent the development of subsequent comorbid psychopathology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Ramp merging is considered as one of the most difficult driving scenarios due to the chaotic nature in both longitudinal and lateral driver behaviors (namely lack of effective coordination) in the merging area. In this study, we have designed a cooperative ramp merging system for connected vehicles, allowing merging vehicles to cooperate with others prior to arriving at the merging zone. Different from most of the existing studies that utilize dedicated short-range communication, we adopt a Digital Twin approach based on vehicle-to-cloud communication. On-board devices upload the data to the cloud server through the 4G/LTE cellular network. The server creates Digital Twins of vehicles and drivers whose parameters are synchronized in real time with their counterparts in the physical world, processes the data with the proposed models in the digital world, and sends advisory information back to the vehicles and drivers in the physical world. A real-world field implementation has been conducted in Riverside, California, with three passenger vehicles. The results show the proposed system addresses the issues of safety and environmental sustainability with an acceptable communication delay, compared to the baseline scenario where no advisory information is provided during the merging process.

Context.— The purpose of this review was to compare 3 coronavirus diseases, including severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses, respectively. Objective.— To cover the following topics: clinical considerations, viral characteristics, pathology, immune response, pathogenesis, and the prognosis associated with each coronavirus disease in humans. Data Sources.— Clinically, flu-like symptoms are usual at the time of presentation for all 3 diseases, but these vary from asymptomatic to severe multisystem involvement. The pathology associated with symptomatic severe acute respiratory syndrome and COVID-19 has been well described, the most prominent of which is diffuse alveolar damage. The immune response to each of these viruses is highly complex and includes both humoral and cellular components that can have a significant impact on prognosis. In severe cases of COVID-19, a dysregulated innate host immune system can initiate a hyperinflammatory syndrome dominated by endothelial dysfunction that can lead to a hypercoagulable state with microthrombi, resulting in a systemic microvascular and macrovascular disease. Conclusions.— The severe acute respiratory syndrome and Middle East respiratory syndrome epidemics have been limited, involving approximately 8000 and 2500 individuals, respectively. In contrast, COVID-19 has resulted in a worldwide pandemic with more than 177 million cases and 3.9 million deaths as of June 15, 2021, and fatality rates ranging from less than 0.1% to approximately 10% depending upon the country. Ending on a positive note, the development of a number of vaccines, at least 6 of which now are in clinical use, should mitigate and eventually control the devastating COVID-19 pandemic.

Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.

Background:Studies have associated HIV with an increased risk of obstructive lung disease (OLD). Objectives:We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. Method:A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. Results:The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = –0.003,P< 0.01), male sex (β = –0.016,P= 0.03) and history of TB or pneumonia (β = –0.024,P< 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47–4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). Conclusion:Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.

Objetivo: O objetivo deste estudo foi testar a hipótese de que a suplementação de cafeína (6 mg · kg-1 de massa corporal) por 4 dias, seguida de ingestão aguda, afetaria a potência de cinco triatletas masculinos após realizarem o exercício de intensidade submáxima. Métodos: Foi realizado um estudo cruzado, randomizado, duplo-cego, placebo-controlado, placebo (4-dias) - placebo (agudo) PP, placebo (4-dias) - cafeína (agudo) PC, cafeína (4-dias) - cafeína (agudo) CC. Os participantes se abstiveram de fontes alimentares de cafeína por 4 dias e ingeriram cápsulas contendo placebo ou cafeína (6 mg.kg-1 de massa corporal por dia). Os participantes nos ensaios agudos ingeriram cápsulas contendo placebo ou cafeína (6 mg.kg-1de massa corporal) 60 minutos antes de realizar o exercício na esteira por 40 minutos (80% VO2máx) e em seguida realizaram o teste de Wingate. O lactato sanguíneo foi determinado antes, 60 minutos após a ingestão, imediatamente após o exercício na esteira e no teste de Wingate e, após 10 min. de recuperação. Resultados: Nos ensaios CC e PC não foram observadas alterações nas variáveis cardiopulmonares (P>0,05) e nas variáveis de potência anaeróbica (potência de pico, potência média e índice de fadiga) (P>0,05). No ensaio PC comparado ao PP promoveu melhorias na curva de potência no tempo de 2 segundos (31,19% - large effect-size d = 1,08; P

Research on intensive agricultural features contributes to the social relations of farming, including the means by which farmers mobilize labor and the possible destination of surplus. Lidar provid...

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.

Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.

Hybrid inorganic/organic heterointerfaces are promising systems for next-generation photocatalytic, photovoltaic, and chemical-sensing applications. Their performance relies strongly on the development of robust and reliable surface passivation and functionalization protocols with (sub)molecular control. The structure, stability, and chemistry of the semiconductor surface determine the functionality of the hybrid assembly. Generally, these modification schemes have to be laboriously developed to satisfy the specific chemical demands of the semiconductor surface. The implementation of a chemically independent, yet highly selective, standardized surface functionalization scheme, compatible with nanoelectronic device fabrication, is of utmost technological relevance. Here, we introduce a modular surface assembly (MSA) approach that allows the covalent anchoring of molecular transition-metal complexes with sub-nanometer precision on any solid material by combining atomic layer deposition (ALD) and selectively self-assembled monolayers of phosphonic acids. ALD, as an essential tool in semiconductor device fabrication, is used to grow conformal aluminum oxide activation coatings, down to sub-nanometer thicknesses, on silicon surfaces to enable a selective step-by-step layer assembly of rhenium(I) bipyridine tricarbonyl molecular complexes. The modular surface assembly of molecular complexes generates precisely structured spatial ensembles with strong intermolecular vibrational and electronic coupling, as demonstrated by infrared spectroscopy, photoluminescence, and X-ray photoelectron spectroscopy analysis. The structure of the MSA can be chosen to avoid electronic interactions with the semiconductor substrate to exclusively investigate the electronic interactions between the surface-immobilized molecular complexes.

Background Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. Methods This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). Results 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 – NFRT: 59.40 vs. RASS -4 – NFRT: 29.00, p < 0.001). Conclusions NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ −4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. Trial Registration Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149.

Background and aim Andrographis paniculata and Eleutherococcus senticosus preparations and their fixed combination, called Kan Jang®, are traditionally used for relieving symptoms of upper-respiratory tract infections (URTIs). This study aimed to assess the efficacy of early intervention with Kan Jang® on the relief and duration of inflammatory symptoms during the acute phase of the disease. Experimental procedure A total of 179 patients with URTI symptoms received six Kan Jang® (daily dose of andrographolides: 60 mg) or placebo capsules a day for five consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group phase II study. The primary efficacy outcomes were the decrease in the acute-phase duration and the mean URTI symptoms score (sore throat, runny nose, nasal congestion, hoarseness, cough, headache, and fatigue). Results Early intervention with Kan Jang® significantly increased the recovery rate and reduced the number of sick leave days by >21% (0.64/day) relative to that observed in the placebo group (2.38 vs. 3.02 days, p = 0.0053). Kan Jang® significantly alleviated all URTI symptoms starting from the second day of treatment. A superior anti-inflammatory effect of Kan Jang® to that of placebo was also observed on the white blood cell count (p = 0.007) and erythrocyte sedimentation rate (p = 0.0258). Treatment with Kan Jang® was tolerated well. Conclusion This study demonstrates that early intervention with Kan Jang® capsules reduces the recovery duration of patients by 21% and significantly relieves the severity of typical URTI symptoms., Graphical abstract Image 1, Highlights Early intervention with Kan Jang® capsules, a fixed combination of Andrographis paniculata and Eleutherococcus senticosus extracts:• Significantly increased patients' recovery rate on days 2, 3, and 4 compared to placebo. • Increased the number of recovered patients by 24% on day 3 compared to placebo control. • Reduced the time to major improvement, defined as the number of sick leave days at home. • Reduced the overall recovery duration time of patients by 21%. • Significantly relieved typical URTI symptoms severity.

This article performs a thermal study through the application of Computational Fluid Dynamics (CFD) of a transformer prototype considering six different cooling configurations. Each configuration was computationally designed and simulated in the ANSYS CFX $$\copyright $$ software. It was possible to analyze the temperature data of the hotspot, at the top oil and at the average temperature, thus comparing the thermal performance of each system and implementing the data in a simplified methodology for estimating the transformer lifespan standardized by IEEE C57.100-2011. In addition, the rendering of the results allows visualizing the temperature distribution and, consequently, the performance for each cooling system. Finally, the advantages and disadvantages of each cooling system were summarized, providing useful information for transformer designer’s decision. As some results, the forced air-cooled transformers have a thermal reduction of approximately 8.81% compared to natural air-cooled and the directed oil system transformers have superior cooling performance than forced oil and natural oil. The directed oil and forced air combination means a useful life 52.76% longer than the natural oil and natural air combination.

PURPOSE: Quantitative susceptibility mapping (QSM) estimates the spatial distribution of tissue magnetic susceptibilities from the phase of a gradient-echo signal. QSM algorithms require a signal mask to delineate regions with reliable phase for subsequent susceptibility estimation. Existing masking techniques used in QSM have limitations that introduce artifacts, exclude anatomical detail, and rely on parameter tuning and anatomical priors that narrow their application. Here, a robust masking and reconstruction procedure is presented to overcome these limitations and enable automated QSM processing. Moreover, this method is integrated within an open-source software framework: QSMxT. METHODS: A robust masking technique that automatically separates reliable from less reliable phase regions was developed and combined with a two-pass reconstruction procedure that operates on the separated sources before combination, extracting more information and suppressing streaking artifacts. RESULTS: Compared with standard masking and reconstruction procedures, the two-pass inversion reduces streaking artifacts caused by unreliable phase and high dynamic ranges of susceptibility sources. It is also robust across a range of acquisitions at 3 T in volunteers and phantoms, at 7 T in tumor patients, and in an in silico head phantom, with significant artifact and error reductions, greater anatomical detail, and minimal parameter tuning. CONCLUSION: The two-pass masking and reconstruction procedure separates reliable from less reliable phase regions, enabling a more accurate QSM reconstruction that mitigates artifacts, operates without anatomical priors, and requires minimal parameter tuning. The technique and its integration within QSMxT makes QSM processing more accessible and robust to streaking artifacts.

Zusammenfassung Ziel der Studie Die aktuelle SARS-CoV-2 Forschung fokussiert sich bisher weitgehend auf symptomatische Fälle. Die STAAB-COVID-Studie untersuchte daher die Seroprävalenz von COVID-19 in der Allgemeinbevölkerung und die psychosozialen Auswirkungen der Pandemie. Methodik Von Juni-Oktober 2020 wurden im Rahmen des STAAB-COVID-Programms, einer Unterstudie der „Häufigkeit und Einflussfaktoren auf frühe STAdien A und B der Herzinsuffizienz in der Bevölkerung (STAAB)“ Kohortenstudie, 4860 Probanden aus einer repräsentativen altersstratifizierten Stichprobe Würzburger Einwohner zur Blutabnahme und Fragebogenerhebung eingeladen. Alle Teilnehmenden erhielten zudem das Angebot, an einer Punktprävalenzerhebung (selbst-entnommener Nasenabstrich Anfang November 2020) teilzunehmen. Ergebnisse Insgesamt nahmen 3034 Probanden am STAAB-COVID-Programm teil (Antwortrate 62%). Bei 33 Teilnehmenden (1,1%; 95% Konfidenzintervall 0,7–1,5%) wurden Antikörper gegen SARS-CoV-2 nachgewiesen. Höhere Werte auf der GAD-7-Angstskala waren mit niedrigeren Raten von SARS-CoV-2-Antikörpern assoziiert (Odds Ratio=0,78 je+1 Punkt im GAD-7; 95% Konfidenzintervall 0,65–0,95). Innerhalb dieser eher ängstlichen Probandengruppe war jedoch auch die Absagerate von medizinischen Terminen erhöht (Odds Ratio=1,13 je+1 Punkt im GAD-7; 95% Konfidenzintervall 1,10–1,16). Bei sechs von insgesamt 2451 Teilnehmenden der Punktprävalenzerhebung (0,24%; 95% Konfidenzintervall 0,09–0,53%) wurde eine akute Infektion nachgewiesen. Schlussfolgerung Zwischen der ersten und zweiten COVID-19 Welle fanden wir in Würzburg eine geringe Durchseuchung mit SARS-CoV-2. Eine ängstlichere Persönlichkeit war dabei mit einer geringeren Seroprävalenz assoziiert. Die Studiendurchführung wurde durch die bereits bestehende Kohortenstudie entscheidend erleichtert.

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Background The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. Methods We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. Results Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). Conclusion We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes.

Image processing techniques are widely used within automotive series production, including production of electronic control units (ECUs). Deep learning approaches have made rapid advances during the last years, but are not prominent in those industrial settings yet. One major obstacle is the lack of suitable training data. We adapt the recently developed method of domain randomization to our use case of 3D pose estimation of ECU housings. We create purely synthetic data with high visual diversity to train artificial neural networks (ANNs). This enables ANNs to estimate the 3D pose of a real sample part with high accuracy from a single low-resolution RGB image in a production-like setting. Requirements regarding measurement hardware are very low. Our entire setup is fully automated and can be transferred to related industrial use cases.

Drawing on the diverse perspectives of four emergency management professionals and a public administration academic, gaps revealed by our nation’s response to the COVID-19 pandemic are discussed. These gaps range from political theory regarding our government system of federalism to fundamental questions around the public communication of risk management and the provision of mass shelter and care.

Background The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p p Conclusion Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

A substantial proportion of children and youth in the child welfare system have mental health concerns that warrant attention. While these youth are more likely to receive treatment in general, they are less likely to receive evidence-based treatments. Cognitive Behavioral Therapy Plus (CBT+) is a training approach in evidence-based treatments for anxiety, depression, behavior problems, and symptoms of traumatic stress. Included in the model is an emphasis on symptom and outcome monitoring. Though based on well-established evidence-based treatments, clinical effectiveness of CBT+ has not been evaluated for child welfare populations. Embedded within a broader initiative called Partnering for Success, the current study evaluated the impact of CBT+ training on treatment outcomes for the mental health symptoms of a racially diverse sample of 1281 children and youth in four different states. Symptom data were collected by community-based mental health therapists as part of standard CBT+ treatment adherence procedures. Multilevel linear growth modeling was used to evaluate symptom change over time. Significant improvements were observed across all four clinical targets, with a slight curvilinear relationship found for anxiety, depression, and behavior problems. This promising initial evidence suggests CBT+ is a viable training option for treatment of child welfare-involved children and youth with a range of mental health concerns.

Background Recent research links problematic smartphone use (PSU) and mental health problems. The purpose of this meta-analysis was to evaluate the relationship between PSU and symptoms of anxiety and/or depression. Methods We searched for research literature published recently in PubMed and Google Scholar via a systematic literature search. Twenty-seven studies published since 2014 with 120 895 participants were included in the meta-analysis. Results PSU was moderately but robustly associated with both anxiety, r = 0.29 (95% CI: 0.23–0.35), and depression, r = 0.28 (95% CI: 0.22–0.34), P Conclusions Our study shows that PSU can be viewed as an indicator of symptoms of anxiety and depression and a possible manifestation of these mental health problems in modern society. Furthermore, PSU as a maladaptive coping behavior may contribute by worsening these symptoms. PSU screening should thus become part of standard clinical psychological diagnostic procedures.

Background. Wearable sensors allow for direct measurement of upper limb (UL) performance in daily life. Objective. To map the trajectory of UL performance and its relationships to other factors post-stroke. Methods. Participants (n = 67) with first stroke and UL paresis were assessed at 2, 4, 6, 8, 12, 16, 20, and 24 weeks after stroke. Assessments captured UL impairment (Fugl-Meyer), capacity for activity (Action Research Arm Test), and performance of activity in daily life (accelerometer variables of use ratio and hours of paretic limb activity), along with other potential modifying factors. We modeled individual trajectories of change for each measurement level and the moderating effects on UL performance trajectories. Results. Individual trajectories were best fit with a 3-parameter logistic model, capturing the rapid growth early after stroke within the longer data collection period. Plateaus (90% of asymptote) in impairment (bootstrap mean ± SE: 32 ± 4 days post-stroke) preceded those in capacity (41 ± 4 days). Plateau in performance, as measured by the use ratio (24 ± 5 days), tended to precede plateaus in impairment and capacity. Plateau in performance, as measured by hours of paretic activity (41 ± 6 days), occurred at a similar time to that of capacity and slightly lagged impairment. Modifiers of performance trajectories were capacity, concordance, UL rehabilitation, depressive symptomatology, and cognition. Conclusions. Upper limb performance in daily life approached plateau 3 to 6 weeks post-stroke. Individuals with stroke started to achieve a stable pattern of UL use in daily life early, often before neurological impairments and functional capacity started to stabilize.

AIMS To develop physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models to predict effective doses of gepotidacin in paediatrics for the treatment of pneumonic plague (Yersinia pestis). METHODS A gepotidacin PBPK model was constructed using a population-based absorption, distribution, metabolism and excretion simulator, Simcyp®, with physicochemical and in vitro data, optimized with clinical data from a dose-escalation intravenous (IV) study and a human mass balance study. A PopPK model was developed with pooled PK data from phase 1 studies with IV gepotidacin in healthy adults. RESULTS For both the PopPK and PBPK models, body weight was found to be a key covariate affecting gepotidacin clearance. With PBPK, ~90% of the predicted PK for paediatrics fell between the 5th and 95th percentiles of adult values except for subjects weighing ≤5 kg. PopPK-simulated paediatric means for Cmax and AUC(0-τ) were similar to adult exposures across various weight brackets. The proposed dosing regimens were weight-based for subjects ≤40 kg and fixed-dose for subjects >40 kg. Comparison of observed and predicted exposures in adults indicated that both PBPK and PopPK models achieved similar AUC and Cmax for a given dose, but the Cmax predictions with PopPK were slightly higher than with PBPK. The two models differed on dose predictions in children

This study evaluates the prognostic impact of anemia in patients presenting with ventricular tachyarrhythmias. The present longitudinal, observational, registry-based, monocentric cohort study included retrospectively all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Anemic patients (hemoglobin levels12.0 g/dl) were compared with non-anemic patients (hemoglobin levels ≥12.0 g/dl). The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were cardiac death at 24 hours, all-cause mortality at index hospitalization, and the composite endpoint of cardiac death at 24 hours, recurrent ventricular tachyarrhythmias, and appropriate ICD therapies at 2.5 years. A total of 2,184 consecutive patients were included, of whom 30% were anemic and 70% non-anemic. Anemia was associated with the primary endpoint of all-cause mortality at 2.5 years (65% vs 29%, p = 0.001; HR = 2.441; 95% CI 2.086 to 2.856), cardiac death at 24 hours (26% vs 11%, p = 0.001), all-cause mortality at index hospitalization (45% vs 20%, p = 0.001), and the composite endpoint (35% vs 27%, p = 0.001; HR = 2.923; 95% CI 2.564 to 4.366). After multivariable adjustment, anemia was no longer associated with the composite endpoint. Predictors of adverse prognosis for anemics were CKD (HR = 2.191), LVEF35% (HR = 1.651), cardiogenic shock (HR = 1.591), CPR (HR = 1.460), male gender (HR = 1.379), and age (HR = 1.017). In conclusion, anemic patients presenting with ventricular tachyarrhythmias were associated with increased long-term mortality at 2.5 years but not with the composite arrhythmic endpoint at 2.5 years. Predictors of adverse prognosis at 2.5 years were CKD, LVEF35%, cardiogenic shock, CPR, male gender, and age.

Background After an acute myocardial infarction (MI 2 ), patients may develop posttraumatic stress disorder (PTSD 3 ). There is evidence for alterations in the hypothalamic–pituitary–adrenal axis in PTSD. An association between patients` cortisol level after experiencing an MI and subsequent PTSD symptoms has not been investigated yet. Therefore, the aim of this study was to examine whether serum cortisol measured in patients admitted to hospital for acute coronary care after MI is predictive of PTSD symptoms at three and 12 months post-MI, respectively. Methods Patients (N=106) with a verified MI and high risk for the development of MI-induced PTSD symptoms were included in the study within 48 hours of hospital admission for acute coronary intervention. Serum cortisol was measured from fasting venous blood samples the next morning. Hierarchical regression analysis was used to test for an independent contribution of cortisol levels from admission to the Clinician-Administered PTSD Scale sum score three and 12 months after discharge from the coronary care unit. Results Hierarchical regression analysis showed that lower serum cortisol levels were significantly associated with more severe PTSD symptoms three months (B=-0.002, p=0.042) and 12 months (B=-0.002, p=0.043) post-MI. Limitations The generalizability of the findings is limited to patients with high acute peri-traumatic distress and without an acute severe depressive episode. The study does not provide any information about the diurnal cortisol pattern. Conclusion Lower serum cortisol measured during MI hospitalization may predict more severe MI-induced PTSD symptoms three and 12 months after hospital discharge.

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Ischemic choroidal diseases are an underdiagnosed entity. The clinical pattern varies according to the size and the localisation of the affected vascular structure.In eyes with occlusion of the long posterior ciliary arteries, characteristic triangular patches of choroidal ischemia (Amalric sign) are seen, which in the course of time merge into well-defined areas of atrophy of the retinal pigment epithelium. Above the non-perfused choroidal areas, hyperpigmented, grouped lines appear (Siegrist streaks). Circumscribed ischemia of smaller choroidal arterioles and capillary vessels appears as multifocal, yellowish lesions in the posterior fundus (Elschnig spots). Vortex vein occlusion becomes manifest as exudative haemorrhagic choroidal swelling in the periphery.Apart from arterial hypertension as a major risk factor, some immunological disorders such as giant cell arteritis and systemic lupus erythematosus and haematological pathologies also affect choroidal perfusion. Furthermore, choroidal ischemia occurs due to local inflammation, as found in eyes with acute multifocal posterior placoid pigment epitheliopathy (APMPPE). Rarely, choroidal infarction is of iatrogenic origin or drug-induced. Recent advances in imaging, such as the introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A), have improved the visualisation of the choroidal vasculature and complement the classical angiographic procedures. In patients with age-related macular degeneration (AMD) and diabetes, some changes in choroidal blood flow and vascular structure have also been noted. While in AMD the choroidal pathologies correlate with the disease progression and the functional prognosis, the pathophysiological relationship between diabetic choroidopathy and retinopathy is currently unclear.With regard to the limited therapeutic options for choroidal ischemia, optimisation of the cardiovascular risk profile and the management of accompanying ocular and systemic diseases are essential.Ischämische Aderhauterkrankungen sind ein unterdiagnostiziertes Krankheitsbild. Die klinischen Zeichen bei chorioidalen Gefäßverschlüssen unterscheiden sich in Abhängigkeit von der Größe und der Lokalisation der betroffenen vaskulären Strukturen.Beim Verschluss der langen posterioren Ziliararterien werden charakteristische trianguläre Aderhautinfarkte (Amalric-Zeichen) beobachtet, die im Verlauf in eine gut abgegrenzte areoläre Atrophie des retinalen Pigmentepithels übergehen und dann als pigmentierte, gruppierte Linien über verschlossenen Aderhautgefäßen erscheinen (Siegrist-Streifen). Die sog. Elschnig-Flecken als multifokale, gelbliche Läsionen am hinteren Pol finden sich bei der Infarzierung kleinerer Arteriolen und kapillärer Aderhautgefäße. Die Thrombosen der Vortexvenen manifestieren sich meist als exsudativ-hämorrhagische Aderhautprominenz in der Peripherie. URSACHEN DER ADERHAUTISCHäMIE: Neben der arteriellen Hypertonie als wesentlichem Risikofaktor sind auch immunologische Systemerkrankungen wie die Riesenzellarteriitis oder der systemische Lupus erythematodes sowie hämatologische Pathologien ätiologisch für das Auftreten von Aderhautischämien bedeutsam. Zudem treten chorioidale Perfusionsstörungen bei lokalen Aderhautentzündungen wie der akuten posterioren multifokalen plakoiden Pigmentepitheliopathie (APMPPE). Selten kann auch eine iatrogen oder medikamentös bedingte Aderhautischämie vorliegen. Durch Fortschritte bei den bildgebenden Verfahren wie die Einführung der Enhanced-Depth-Imaging-Technik bei der optischen Kohärenztomografie (EDI-OCT) und die OCT-Angiografie (OCT-A) wurde die Darstellbarkeit der chorioidalen Perfusion ergänzend zu den klassischen angiografischen Untersuchungen in den letzten Jahren deutlich optimiert. Hierbei wurden auch bei der altersabhängigen Makuladegeneration (AMD) und beim Diabetes mellitus Anzeichen für eine chorioidale Perfusionsstörung und veränderte Aderhautstruktur gefunden. Während bei der AMD das Ausmaß der chorioidalen Veränderungen mit der Progression und der funktionellen Prognose zu korrelieren scheint, ist der pathophysiologische Zusammenhang zwischen diabetischer Chorioidopathie und Retinopathie derzeit unklar.Aufgrund der eingeschränkten Therapiemöglichkeiten bei Aderhautischämie sind die Optimierung des kardiovaskulären Risikoprofils und das Management begleitender Augen- oder Systemerkrankungen essenziell.

When two skilled human workers cooperate on a task, such as moving a sofa through a tight doorway, they often infer what needs to be done without explicit communication because they have learned cooperation skills from their prior work or training. This paper extends that concept to a two-robot team. The robots are given the task to carry a large payload through a narrow doorway while avoiding obstacles within the room. System dynamics and sensor noise were included in the study. Each robot is independently controlled with the knowledge of the goal location, its own position, and the pose of the payload. The decentralized control uses a Genetic Fuzzy System for each robot to learn its own decision-making skill through a training process without a pre-planned motion trajectory. The introduction of a genetic algorithm adds efficiency to the process of determining the shape of the fuzzy logic membership functions by using an evolutionary search algorithm to tune each parameter in the fuzzy system simultaneously. The contribution of this paper is to illustrate how genetic training can tune a simple, decentralized Fuzzy Logic System based on a given scenario and then be used, unaltered, for a scenario beyond that for which it was trained. The extended scenarios introduce unknown obstacles, new sizes and mass properties for the robots and payload, and random initial positions. The effectiveness of this approach for a 2D case is determined by dynamic simulation with results starting at a 95% success rate for the baseline scenario and 84% for the scenario that was extended furthest from how it was originally trained.

Introduction The Salford Lung Studies (SLS) were real-world randomised controlled trials set within UK primary care that assessed the effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol versus continuing usual care in patients with chronic obstructive pulmonary disease or asthma. Data were collected for a relatively short period, limiting the study of long-term outcomes. To broaden the capture of SLS patients’ data, we undertook the Extended SLS (Ext-SLS), aiming to better understand the patient disease journey and the effects of treatment in a real-world setting, through collection of patient-level data. Here, we present study design information and the challenges and learnings gathered in creating the Ext-SLS. Methods The Ext-SLS was intended to augment the SLS by collecting retrospective and prospective (up to 10 years from consent) primary and secondary care electronic health record (EHR) data and patient questionnaires. After ethics approval, general practitioners (GPs) obtained consent from SLS patients remotely (mean 3.2 years post-SLS completion). To facilitate GPs identifying eligible patients, a novel EHR-based approach flagged SLS patients who were alive and registered with their original GP. An automated system sent consent forms/questionnaires to patients. Medical data were collected via EHRs; primary care data were extracted from GPs’ systems whilst secondary care data were sourced from the UK NHS. Results Of the 75 GP sites from the SLS, 35 (47%) declined Ext-SLS participation leaving 4158 potentially eligible patients; 1169 (28%) patients were excluded as GPs could not confirm them as SLS participants or due to incapacity. Of 2989 patients invited, 1189 (40%) consented. Conclusions Developing an EHR-based trial extension was achieved, with reasonable consent rates amongst invited patients. The resulting Ext-SLS is a unique and valuable research resource. Leveraging EHRs and technology reduced GP burden, facilitating participation. Initiation of extension studies prior to study close-out may help increase GP and patient participation. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01827-2.

ZusammenfassungDas Virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus Type 2) und die von ihm ausgelöste Erkrankung COVID-19 (Coronavirus Disease 2019) können zahlreiche Organsysteme betreffen. In vorliegender Arbeit bieten wir einen Überblick bezüglich des aktuellen Wissensstands über die psychiatrischen Aspekte der SARS-CoV-2 Infektion.Die Datenbanken Medline, Embase und LIVIVO wurden nach relevanter Literatur untersucht, die letzte Abfrage erfolgte am 02.03.2021. Unterschiedliche Stressfaktoren im Rahmen der Epidemie können zu manifesten psychischen Erkrankungen führen. Zusätzlich besteht das Risiko psychischer Veränderungen durch die biologischen Effekte des Virus selbst.Beschrieben werden in unserer Arbeit psychische Symptome von an COVID-19 Erkrankten selbst sowie die psychischen Auswirkungen der Epidemie und der damit einhergehenden sozioökonomischen und psychosozialen Stressfaktoren auch auf nicht Erkrankte.Bei an COVID-19 Erkrankten zeigen sich als häufigste psychiatrische Komplikation das Auftreten von Delirien, bei hospitalisierten Patienten scheint es zu gehäuftem Auftreten von Symptomen von Angst, Depression und posttraumatischen Belastungsstörungen zu kommen. Es liegen auch zahlreiche Kasuistiken über psychotische Störungen vor. Allgemein steigert eine vorliegende psychiatrische Erkrankung (besonders eine psychotische oder dementielle Störung) auch das Risiko einer Infektion und eines schweren Verlaufes. Nach Ablauf einer COVID-19-Infektion ist ebenfalls eine höhere Inzidenz von psychischen Erkrankungen zu finden, hier ist das „Chronic Post-SARS Syndrome“ mit seinen Ausprägungen wie Fatigue, Angst, Depression und PTSD zu nennen. Außerdem scheint der Verlauf einer dementiellen Erkrankung durch eine Infektion mit SARS-CoV-2 negativ beeinflusst zu werden.Ferner wird auf die Auswirkungen eingegangen, die das Bedrohungsszenario der Epidemie und die etablierten gesellschaftlichen Schutzmaßnahmen auf die psychische Gesundheit von Menschen mit und ohne psychische Vorerkrankungen haben. Es zeigen sich hier in der derzeit vorliegenden Literatur hohe Symptomwerte betreffend Angst- und depressiven Störungen sowie posttraumatischen Belastungsstörungen, Stress, Suizidalität, Schlafstörungen, etc. Risikofaktoren scheinen unter anderem weibliches Geschlecht, jüngeres Alter und geringere Ressourcen sowie psychische oder körperliche Vorerkrankungen darzustellen. Extrinsische Faktoren wie z-B. hohes Infektionsgeschehen, große Anzahl von Todesfällen, lange Ausgangssperren/Lockdowns, geringes Vertrauen in die Regierung und ineffektive Maßnahmen gegen wirtschaftliche und soziale Folgen steigern die Belastung.

Diabetic macular edema (DME) is a chronic retinal disease, which requires intensive clinical monitoring. Within the last ten years the intravitreal anti-VEGF (vascular endothelial growth factor) therapy has become the standard of care to improve and stabilize vision in patients with centre involving DME. Long-acting intravitreal corticosteroids can achieve similar visual results with fewer injection rates. Because of steroid-induced side effects (progression of cataract, glaucoma) these drugs are regarded as second-line medication. Since the introduction of anti-VEGF-medication the focal laser photocoagulation is no longer considered as first-line therapy for DME. However, a focal laser treatment can sometimes be a possible alternative in specific situations. In patients with proliferative diabetic retinopathy and DME, the intravitreal anti-VEGF therapy is approved for both conditions. In ischemic maculopathy the functional outcome is restricted. For the indication of anti-VEGF-treatment for DME with accompanying central ischemia not only visual acuity and optical coherence tomography parameters should be considered, the amount of ischemia seen on fluorescein angiography should also be taken into account. In tractional macular edema due to epiretinal membranes and vitreomacular adhesions a pars-plana vitrectomy with membrane peeling is indicated.

Background Implantable cardioverter-defibrillators (ICDs) are an effective treatment in some patients with inherited heart disease, including inherited channelopathies, yet they have also been shown to impact patients' psychological health. Objective We sought to improve understanding of the level of anxiety and depression as well as device acceptance among inherited channelopathy patients with an ICD. Methods Eligible patients seen at Johns Hopkins Hospital were sent a survey, which included the Hospital Anxiety and Depression Scale (HADS), Cardiac Anxiety Questionnaire (CAQ), and the Florida Patient Acceptance Survey (FPAS). Student t tests and χ2 tests were used to identify associations with abnormal anxiety and depression scores. Results Among eligible patients (n = 65), 32 individuals (49%) completed the survey. The rate of device-related complications was 34%, and 41% of patients experienced 1 or more ICD shocks. Twelve patients (38%) had an abnormal HADS anxiety subscore and 5 patients (16%) had an abnormal HADS depression subscore (score ≥ 8). Secondary-prevention ICDs were associated with an abnormal HADS anxiety subscore (P = .03). Experiencing ICD shock(s), device complications, age, sex, and family history of sudden cardiac death were not statistically associated with anxiety or depression. Overall, respondents demonstrated high device acceptance by FPAS (79.9 ± 2.9, maximum total score 100) and moderately high cardiac-specific anxiety by CAQ total score (1.53 ± 0.12). Conclusion A high prevalence of generalized anxiety was identified among inherited channelopathy patients with ICDs. High device acceptance and lack of association with ICD shocks or complications indicate that further research is necessary to understand this increased incidence.

Following the recent mass migration of refugees to the European Union in 2015 and 2016, many EU countries took significant steps aimed at improving the socio-economic integration of the refugees. This study examines refugee entrepreneurship in rural areas in Sweden as evidenced in the agri-food industry. Entrepreneurship is often considered a sustainable activity that can promote refugees' economic independence and social integration. The rural setting offers promising employment opportunities for refugees with agricultural backgrounds or interest. Qualitative research methodology, based on 25 in-depth, semi-structured interviews with refugees, is used to examine refugee entrepreneurs’ experiences in the various phases of the entrepreneurial process, from start-up and growth to success/exit. The study found that refugee entrepreneurs are motivated and challenged variously as they start and operate their entrepreneurial activities. For example, they are motivated by the discovery of niche markets, previous entrepreneurial experience, and the availability of family and government support. Challenges include legislative hurdles, management and technical problems, and insufficient financial and other support. Factors both within and outside their control influence the survival of their entrepreneurship.

Objective: Ultra-high-field B0 ≥ 7 tesla (7T) cardiovascular magnetic resonance (CMR) offers increased resolution. However, electrocardiogram (ECG) gating is impacted by the magneto-hydrodynamic effect distorting the ECG trace. We explored the technical feasibility of a 7T magnetic resonance scanner using an ECG trigger learning algorithm to quantitatively assess cardiac volumes and vascular flow. Methods: 7T scans were performed on 10 healthy volunteers on a whole-body research MRI MR scanner (Siemens Healthineers, Erlangen, Germany) with 8 channel Tx/32 channels Rx cardiac coils (MRI Tools GmbH, Berlin, Germany). Vectorcardiogram ECG was performed using a learning phase outside of the magnetic field, with a trigger algorithm overcoming severe ECG signal distortions. Vectorcardiograms were quantitatively analyzed for false negative and false positive events. Cine CMR was performed after 3rd-order B0 shimming using a high-resolution breath-held ECG-retro-gated segmented spoiled gradient echo, and 2D phase contrast flow imaging. Artefacts were assessed using a semi-quantitative scale. Results: 7T CMR scans were acquired in all patients (100%) using the vectorcardiogram learning method. 3,142 R-waves were quantitatively analyzed, yielding sensitivity of 97.6% and specificity of 98.7%. Mean image quality score was 0.9, sufficient to quantitate both cardiac volumes, ejection fraction, and aortic and pulmonary blood flow. Mean left ventricular ejection fraction was 56.4%, right ventricular ejection fraction was 51.4%. Conclusion: Reliable cardiac ECG triggering is feasible in healthy volunteers at 7T utilizing a state-of-the-art three-lead trigger device despite signal distortion from the magnetohydrodynamic effect. This provides sufficient image quality for quantitative analysis. Other ultra-high-field imaging applications such as human brain functional MRI with physiologic noise correction may benefit from this method of ECG triggering.

Data availability all datasets used in this study are available on the web at the following addresses (see also the manuscript):- https://www.usgs.gov/volcanoes/kilauea/monitoring- https://www.usgs.gov/observatories/hawaiian-volcano-observatory- https://pnsn.org/seismograms- https://www.pnsn.org/tremor- http://www.fdsn.org/networks/detail/Y4_2014.; International audience; Data visualization, and to a lesser extent data sonification, are classic tools to the scientific community. However, these two approaches are very rarely combined, although they are highly complementary: our visual system is good at recognizing spatial patterns, whereas our auditory system is better tuned for temporal patterns. In this article, data representation methods are proposed that combine visualization, sonification, and spatial audio techniques, in order to optimize the user’s perception of spatial and temporal patterns in a single display, to increase the feeling of immersion, and to take advantage of multimodal integration mechanisms. Three seismic data sets are used to illustrate the methods, covering different physical phenomena, time scales, spatial distributions, and spatio-temporal dynamics. The methods are adapted to the specificities of each data set, and to the amount of information that the designer wants to display. This leads to further developments, namely the use of audification with two time scales, the switch from pure audification to time-modulated noise, and the switch from pure audification to sonic icons. First user feedback from live demonstrations indicates that the methods presented in this article seem to enhance the perception of spatio-temporal patterns, which is a key parameter to the understanding of seismically active systems, and a step towards apprehending the processes that drive this activity.

We evaluated long range antennae and associated solar-powered global positioning system (GPS) ear tags designed for use with domestic cattle, as a novel system for monitoring ranging behaviour of the koala (Phascolarctos cinereus). The mean location error of our GPS tags was 33.9 m (s.e. = 0.46). The tags were relatively light (30 g), reported eight locations per day when attached to koala radio-collars and had an operating life that exceeded our study period (8 months). Deployed as a stand-alone, solar powered, remote system, this technology can provide a viable option for wildlife tracking projects.

AIMS Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

In order to advance the development of molecular electronic devices, it is mandatory to improve the understanding of electron transport and functionalities in single molecules, integrated in a well-defined environment. However, limited information can be obtained by solely analyzing I-V characteristics, whence multiparameter studies are required to obtain more information on such systems including chemical bonds, geometry, and intramolecular strain. Therefore, we developed an analytical method incorporating an optical near-field technique, which allows us to investigate single-molecule junctions at variable temperatures in strong optical fields. An apertureless near-field emitter acts as a counter electrode and a plasmonic waveguide to focus surface plasmon polaritons into the molecular junctions, where a strongly enhanced evanescent field is confined to only a few nanometers around the apex of the tip. The proof of concept, even at low temperatures, is demonstrated by simultaneously investigating electronic and optical features of the molecule p-terphenyl-4,4″-dithiol in dependence of its charge state. This multichannel method can be employed to analyze a variety of nearly unexplored properties in single-molecule junctions such as photoconductance and photocurrent generation and allows a characterization of the molecular junctions by spectroscopic means as well.

Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4+ and CD8+ T cells. The majority of CD4+ T-helper cells were localized in the upper dermis, whereas cytotoxic CD8+ T cells were found in the epidermis. Increased numbers of CD56+ natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.

Introduction Posterior Reversible Encephalopathy Syndrome (PRES) and the related term Reversible Posterior Leukoencephalopathy Syndrome (RPLS) denote a constellation of clinical symptoms paired with key radiological findings. These symptoms may include headache, altered mental status, visual changes, and seizures. PRES is a rare condition and remains a challenging diagnosis to make in the emergency department. Data on risk factors and clinical presentation are limited, and there is no recent literature-supported diagnostic criteria. Our primary objective was to identify initial symptoms, clinical presentation, and risk factors that should guide the emergency clinician to consider a diagnosis of PRES. A secondary objective was to identify associations between risk factors and the outcomes of mortality and ICU admissions. Methods This was a retrospective, observational study that evaluated patients seen in the Emergency Department (ED) in an urban tertiary care center with the diagnosis of PRES or RPLS from 1/1/2008 to 1/1/2018. The Health System’s Electronic Medical Record was used to collect data. Search criteria included any patient diagnosed with Posterior Reversible Encephalopathy Syndrome (PRES) or Reversible Posterior Leukoencephalopathy Syndrome (RPLS), and excluded patients under 18 years of age, transfer patients, or patients that were not evaluated in our emergency department. Results We identified 98 patients based on our initial search criteria. After a chart review, 27 patients met our predefined eligibility criteria. In patients with confirmed diagnosis of PRES, the majority were female (70%) and 37% were either on an immunomodulator or undergoing chemotherapy at the time of presentation. 67% of patients presented with altered mental status, 41% had a focal neurologic deficit, and 37% had a witnessed seizure prior to diagnosis. Headache (48%), nausea (33%), and vision changes (30%) were the next most common reported symptoms. The majority of patients were hypertensive at time of presentation (82%) and many had a past medical history of hypertension (78%); twelve were given anti-hypertensive medications. 33% of the patients were admitted to the ICU and 26% died. There were no statistical associations found between documented ED interventions and the outcome of mortality. Conclusion PRES is difficult to identify and diagnose in the emergency department. Significant risk factors such as female gender, hypertension, and those currently undergoing active immunotherapy/chemotherapy are associated with PRES. Common presenting complaints and exam findings include headache, altered mental status, and neurologic deficits. Emergency providers should consider PRES in patients presenting with altered mental status with significant risk factors, especially with neurologic deficits for which stroke has been ruled out.

We report a case series of 4 patients with transient marked QTc prolongation and ventricular arrhythmias in the setting of inflammation with very high ferritin levels. Three patients were positive for coronavirus disease-2019. In the setting of an acute rise in inflammatory markers, electrocardiography screening for QTc prolongation is warranted. (Level of Difficulty: Beginner.), Central Illustration

Background Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX are standard first-line treatment options for advanced pancreatic ductal adenocarcinoma (aPDAC), but currently no prospective randomised head-to-head comparison between these treatments has yet been performed. Methods We conducted a comparative propensity score (PS) analysis of overall (OS) and progression-free survival (PFS) in a tri-centre cohort of patients with aPDAC undergoing palliative first-line treatment with either GN or FOLFIRINOX. Results In unadjusted analysis, OS and PFS were highly similar between patients treated with GN (n = 297) and FOLFIRINOX (n = 158). In detail, median, 1- and 2-year OS estimates were 10.1 months, 42% and 18% in the GN group, as compared to 11.2 months, 45% and 12% in the FOLFIRINOX group, respectively (log-rank p = 0.783). Accordingly, median (4.6 versus 4.8 months), 6-month (40% versus 43%) and 1-year (9% versus 9%) PFS estimates did not significantly differ (log-rank p = 0.717). However, patients treated with FOLFIRINOX were significantly younger, had fewer comorbidities, and a better Eastern Cooperative Oncology Group performance status. These imbalances were accounted for by weighting the data with the PS. In PS analysis of survival outcomes, OS and PFS remained comparable between the two treatment groups. In detail, PS-weighted median, 1- and 2-year OS estimates were 10.1 months, 42% and 18% in the GN group, as compared to 10.1 months, 40% and 13% in the FOLFIRINOX group (PS-weighted log-rank p = 0.449). PS-weighted PFS estimates again did not differ (PS-weighted log-rank p = 0.329). Conclusion This real-world comparative effectiveness study indicates that FOLFIRINOX and GN have similar effectiveness in the palliative first-line treatment of aPDAC.

Introduction Recent work reveals a new source of error in number line estimation (NLE), the left digit effect (Lai, Zax, et al., 2018), whereby numerals with different leftmost digits but similar magnitudes (e.g., 399, 401) are placed farther apart on a number line (e.g., 0 to 1,000) than is warranted. The goals of the present study were to: (1) replicate the left digit effect, and (2) assess whether it is related to mathematical achievement. Method Participants were all individuals (adult college students) who completed the NLE task in the laboratory between 2014 and 2019 for whom SAT scores were available (n = 227). Results We replicated the left digit effect but found its size was not correlated with SAT math score, although it was negatively correlated with SAT verbal score for one NLE task version. Conclusions These findings provide further evidence that individual digits strongly influence estimation performance and suggest that this effect may have different cognitive contributors, and predict different complex skills, than overall NLE accuracy., We replicate the recently discovered left digit effect in number line estimation. Unlike overall accuracy, the left digit effect is not correlated with math achievement, suggesting a different cognitive source.