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INTRODUCTION: The nose and throat are areas of high viral load, which could place otolaryngologists at an even higher risk for COVID-19 than other health-care workers. OBJECTIVE: To investigate the prevalence of antibodies against SARS-CoV-2 in otorhinolaryngologists in southern Brazil, its relationship to demographic data, professional practice and reported symptoms of COVID-19, and compare it with official data on other health-care workers of the state and the general population in the same period. METHODS: In this cross-sectional multicenter study, otolaryngologists actively practicing officially registered in Rio Grande do Sul were screened for IgM and IgG antibodies against SARS-CoV-2 from August 1 to September 15, 2020. A questionnaire was also applied. RESULTS: We screened 358 (80.1%) of 447 actively practicing otolaryngologists (195 [54.5%] male; mean [SD] age, 47.77 [13.57] years; range, 26-84 years). Twenty-three were positive for IgM and/or IgG (6.4%). This result was significantly associated with reports of infected household contacts (19/315 negatives and 8/23 positives; p 

Private sector actors are taking on an increasingly prominent role in energy transitions, including in hydropower development and finance. Yet, there is little empirical research on the topic. This study covers private sector views on accelerating hydropower investment in Nepal, using Q methodology. Three main viewpoints were identified among 17 interviewed hydropower developers, planners, and investors based in Nepal: 1) Efforts need to be focused on reforming hydropower policies and administration at the national level; 2) Funds for hydropower development need to be increased and sought from a diversity of domestic and foreign private sources; 3) Nepal needs to integrate its energy grid with its South Asian neighbours, starting with India. Areas of strong disagreement include the role of political stability in enabling hydropower development, as well as modes of engagement with Indian, Chinese, and Western partners. Areas of consensus include the need to smoothen land acquisition procedures as well as discomfort with the state-owned Nepal Electricity Authority’s perceived monopolistic status in the sector. Overall, this study contributes to debates on private sector involvement in hydropower development with a nuanced empirical assessment of views which contain clear visions for an independent and domestically driven future of the country’s hydropower sector. Postprint

Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer’s disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aβ), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. 18F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer 18F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo 18F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that 18F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.

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.

ZusammenfassungUnter dem Begriff „menschliches Mikrobiom“ wird der Komplex aus Mikroorganismen – Bakterien, Viren, Pilze, Protozoen und Archaeen –, welche die Oberflächen, Gewebe und Flüssigkeiten des menschlichen Körpers besiedeln, zusammengefasst. Sie haben eine offensichtliche Rolle bei der Kanzerogenese und mit der Verbreitung neuer Hochdurchsatz-Sequenzierungsmethoden ist die Untersuchung dieser mikrobiellen Gemeinschaften wesentlich einfacher geworden. Diese Übersichtsarbeit beschreibt die aktuell verfügbare Evidenz über die Rolle des Mikrobioms bei der gastrointestinalen Karzinogenese.

This article discusses the underground cinema of the German Democratic Republic during the 1980s in regard to its contributions to the arts and the avant-garde. While scholars including Claus Löser and Katrin Frietzsche have contributed greatly to the remembrance of the East German underground cinema, its influences have been disregarded by film studies, not least within the anglophone field. As a result, little to no research has been conducted regarding its contributions to the avant-garde or through the scope of other art movements as the political aspect continues to be emphasized. This article draws upon multiple art developments such as dada, surrealism, performance and body art as well as Eastern European-specific movements. Therefore, it evaluates how the East German underground interprets those influences and further contributes to them. Significant works by Cornelia Schleime, Gabriele Stötzer, Thomas Frydetzki and Tohm di Roes are subject to analyses to reveal anarchist feminist tendencies and surrealism with anarchist aspects. It concludes that the East German underground must be seen as a contribution to the less-researched necrorealism as an art movement paralleling the constitutional socialist realism. As such, political implications cannot be subtracted altogether but shall rather be viewed alongside the emergence of anarchist surrealism during the Cold War.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

This work aims to present and discuss a complete model for the analysis of compound solar sail performance for the simple solar photon thruster configuration. A nonideal formulation of the problem ...

A ideia de comércio justo, ético e solidário está relacionada a um processo de intercâmbio comercial orientado para a valorização e reconhecimento do trabalho e das expectativas de produtores e consumidores. Práticas que visam incentivar a economia local, seja no âmbito da produção ou do consumo, requerem estratégias de marketing bem estruturadas e elaboradas. O objetivo deste trabalho é discutir as potencialidades do marketing como forma de promoção e fortalecimento dos empreendimentos de economia solidária através dos 4 P’s do composto de marketing. A pesquisa foi realizada durante a 21ª FEICOOP e 10ª Feira Latino Americana de Economia Solidária, caracterizando-se como um levantamento de campo. O presente estudo apresenta uma amostra de 140 formulários aplicados no público da feira durante os dias 18, 19 e 20 de julho de 2014. Os resultados indicam que o público acredita que a internet é o melhor local para divulgação dos produtos, considerando muito boa a ideia de um site para divulgação dos mesmos. Conclui-se que nos empreendimentos de economia solidária o produtor é o principal responsável pela realização dos quatro elementos que compõe o composto de marketing.

Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.Methods and Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradio-therapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade >= 1 or >= 2 was scored in at least half of the follow ups.Results: The median follow-up time was 57 months. Baseline fatigue grade >= 1/>= 2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade >= 1/>= 2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade >= 2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade >= 1 increased by 7% and 4% with V43Gy 3000 cm(3) in patients with and without baseline fatigue, respectively. Late persistent grade >= 1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques. (C) 2021 Elsevier Inc. All rights reserved.

This paper puts forward the framework of the 'marketplace of post-conflict assistance' as a conceptual, analytical, and heuristic tool to comprehend better holistic dynamics in humanitarian and post-conflict contexts, where a variety of different actors offer various services and forms of assistance. It seeks to emphasise relations and interactions between service providers and intended beneficiaries in settings where there are often numerous different ways to conceptualise and manage problems stemming from armed conflict. This is demonstrated using one in-depth case study of a family in northern Uganda that has struggled for years with mental illness/spiritual problems. By framing the post-conflict space using the marketplace metaphor, it is possible to deepen understanding of how people try out different options to manage issues related to warfare and seek healing. Importantly, this framework also recognises the agency that people exercise in doing so, and how communities and service providers relate to each other.نطرح في هذه المقال إطار عمل "سوق المساعدة في مرحلة ما بعد الصراع" كأداة مفاهيمية وتحليلية وإرشادية لفهم الديناميكيات الشاملة التي تحدث في السياقات الإنسانية وسياقات ما بعد الصراع بشكل أفضل، حيث توجد مجموعة متنوعة من الجهات الفاعلة المختلفة التي تقدم أشكال مختلفة من الخدمات والمساعدة. من خلال هذا الإطار المفاهيمي، نسعى إلى التأكيد على الديناميكيات العلائقية والتفاعلية بين مقدمي الخدمات والمستفيدين المقصودين في سياقات حيث توجد غالبًا مجموعة متنوعة من الطرق المختلفة لتصور وإدارة المشكلات الناشئة عن سنوات من النزاع المسلح. نوضح ذلك من خلال دراسة حالة واحدة متعمقة لعائلة كافحت لسنوات مع مرض عقلي / مشاكل روحية في السنوات أثناء وبعد النزاع المسلح في شمال أوغندا. من خلال تأطير مساحة ما بعد الصراع من خلال استعارة السوق، يصبح من الممكن اكتساب فهم أكثر شمولية وديناميكية للطرق التي يجرب بها الناس خيارات مختلفة لإدارة القضايا المتعلقة بسنوات من النزاع المسلح والسعي للشفاء. والأهم من ذلك، فإن هذا الإطار يتعرف أيضًا بالوكالة التي يستعملها الناس في القيام بذلك، وكيف ترتبط المجتمعات ومقدمي الخدمات في السياقات الإنسانية والتنموية وسياقات ما بعد الصراع ببعضهم البعض. كلمات مفتاحية : وكالة، الأنثروبولوجيا، التنمية، التعددية العلاجية، الإنسانية، ما بعد الصراع، أوغندا.在本文中，我们提出了“冲突后援助市场”的框架，作为一种概念性、分析性和启发式工具，以更好地理解人道主义和冲突后环境中发生的整体动态，其中有各种不同的行为者提供各种形式的服务和援助。通过这个概念性框架，我们试图强调服务提供者和预期受益者之间的关系和互动动态，在这种情况下，通常有多种不同的方式来概念化和管理多年武装冲突引起的问题。我们通过对一个在乌干达北部武装冲突期间和之后多年来一直与精神疾病/精神问题作斗争的家庭进行的深入案例研究来说明这一点。通过市场隐喻来构建冲突后空间，就有可能对人们尝试不同选择来管理与多年武装冲突相关的问题并寻求治愈的方式进行更全面和动态的理解。重要的是，这个框架还承认人们在这样做的时候所行使的权力，以及在人道主义、发展和冲突后背景下的社区和服务提供者之间的关系。 关键词：权力, 人类学, 发展, 治愈多元主义, 人道主义, 冲突后, 乌干达.

Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has expanded and spearheaded development in hepatobiliary surgery. Monosegment-ALPPS tests liver regeneration limits and may present as the last feasible curative treatment option. Methods Electronic databases (MEDLINE, Web of Science, Google Scholar, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on mono-ALPPS using a predefined strategy without date or language restrictions. Individual patient data was extracted and analyzed. Results 237 publications were identified. 19 patients were identified to have undergone mono-ALPPS. Primarily, mono-ALPPS has been utilized as curative treatment for CRLM (17 of 19 cases). Successful mono-ALPPS was possible in FLR above 8% SLV. All patients received either chemotherapy alone or in combination with radiotherapy prior to surgery. 8 of 19 patients experienced PHLF grade A or B. There was no in-hospital mortality described. Recurrent disease has occurred in 7 of 19 patients and 3 have died during follow-up. Conclusion Mono-ALPPS is an experimental procedure that provides a reasonably safe opportunity to curatively treat extensive liver malignancies in patients with FLR as low as 8% SLV. PHLF is the most prevalent complication in mono-ALPPS. Mono-ALPPS should be evaluated in a multicentral study setting.

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2). Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = –0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

Purpose: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer.Methods and materials: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of = .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques.Results: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade =3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade >= 2 diarrhea, and 26.1% (vs 13.1%) had grade >= 2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences.Conclusions: IMRT resulted in fewer grade >= 3 AEs during treatment and significantly lower rates of grade >= 2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps were observed after IMRT compared to 3DCRT. (C) 2021 The Authors. Published by Elsevier Inc.

BackgroundChronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections. The present study addresses this disparity by taking the individual perspective of pain patients into account, which is the varying intensity of endogenous pain.MethodsTo this end, we investigated the cortical encoding of 20 chronic back pain patients and 20 chronic migraineurs in four repeated fMRI sessions. During the recording, the patients were asked to continuously rate their pain intensity. A brain parcellation approach subdivided the whole brain into 408 regions. A 10 s sliding-window connectivity analysis computed the pair-wise and time-varying connectivity between all brain regions across the entire recording period. Linear mixed effects models were fitted for each pair of brain regions to explore the relationship between cortical connectivity and the observed trajectory of the patients’ fluctuating endogenous pain.ResultsTwo pain processing entities were taken into account: pain intensity (high, middle, low pain) and the direction of pain intensity changes (rising vs. falling pain). Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. For chronic back pain this applies to the pain intensity-related connectivity for limbic and cingulate areas, and for the precuneus. The change of pain intensity was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and ACC regions.ConclusionsInterestingly, the group results were not mirrored by the individual patterns of pain-related connectivity, which is suggested to deny the idea of a common neuronal core problem for chronic pain diseases. In a similar vein, our findings are supported by the experience of clinicians, who encounter patients with a unique composition of characteristics: personality traits, various combinations of symptoms, and a wide range of individual responses to treatment. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.

Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p 15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

This study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States.Despite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing.From the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined.Out of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively.In a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

Within the last years, Q CELLS has developed a silicon solar cell structure yielding an energy conversion efficiency exceeding 24%. The cell structure features a so-called passivating contact consisting of an interfacial oxide and an n-type polysilicon layer on the rear side, double-sided screen-printed metal contacts, a module-optimized anti-reflective coating, a homogeneous front-side emitter, and an n-type silicon substrate. For the fabrication of this type of solar cell, a lean processing sequence has been applied by using exclusively mass-production processes in Q CELLS’ pilot R&D line in Thalheim, Germany. For module integration, state-of-the-art technology, such as half-cells, multi-wire interconnection, standard encapsulants, and zero-gap technology, can be applied. Hence, this solar cell structure has the potential to fully close the small remaining gap to the highest efficiency cell technologies, such as heterojunction and rear-contact solar cells at very competitive manufacturing cost. In analogy to Q CELLS' PERC-like Q.ANTUM technology, and in contrast to conventional passivated emitter and rear cells (PERC), this novel solar cell is shown to reliably suppress light-induced degradation.

Background COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV1 in chronic HF. Research Question Is pulmonary function related to the progression of chronic HF? Study Design and Methods The MyoVasc study ( ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF. Results Overall 2,998 participants (age range, 35-84 years) with available FEV1 data were eligible for analysis. Linear multivariate regression analysis revealed an independent relationship of FEV1 (per –1 SD) with deteriorated systolic and diastolic left ventricle (LV) function as well as LV hypertrophy under adjustment of age, sex, height, cardiovascular risk factors (CVRFs), and clinical profile (LV ejection fraction: β-estimate, –1.63% [95% CI, –2.00% to –1.26%]; E/E′ ratio: β-estimate, 0.82 [95% CI, 0.64-0.99]; and LV mass/height2.7: β-estimate, 1.58 [95% CI, 1.07-2.10]; P Interpretation FEV1 represents a strong candidate to improve future risk stratification and prevention strategies in individuals with chronic, stable HF. Trial Registry ClinicalTrials.gov; No.: NCT04064450; URL: www.clinicaltrials.gov

By promising more accurate diagnostics and individual treatment recommendations, deep neural networks and in particular convolutional neural networks have advanced to a powerful tool in medical imaging. Here, we first give an introduction into methodological key concepts and resulting methodological promises including representation and transfer learning, as well as modelling domain-specific priors. After reviewing recent applications within neuroimaging-based psychiatric research, such as the diagnosis of psychiatric diseases, delineation of disease subtypes, normative modeling, and the development of neuroimaging biomarkers, we discuss current challenges. This includes for example the difficulty of training models on small, heterogeneous and biased data sets, the lack of validity of clinical labels, algorithmic bias, and the influence of confounding variables.

Two-dimensional thermographic particle image velocimetry (T-PIV) is presented for the in situ measurement in optically accessible internal combustion (IC) engines. Temperature and velocity measurements are combined using thermographic phosphor particles as tracers for PIV. For three commercially available phosphors (BAM:Eu2+, ZnO, and ZnO:Zn), temperature sensitivity, luminescence intensity at high temperatures and laser-fluence dependence were evaluated for phosphor-coated surfaces in a high-temperature cell. ZnO:Zn was identified as the best-suited candidate for engine in-cylinder measurements and further analyzed in the aerosolized state at temperatures up to 775 K to generate calibration data required for signal quantification in engine experiments. T-PIV was successfully applied in the IC engine to simultaneously obtain instantaneous two-dimensional velocity and temperature fields using the intensity-ratio method. Despite a measurement uncertainty (±1σ basis) of only 3.7 K at 317 K (1.2%) to 24.4 K (4.2%) at 575 K, this technique suffers from low signal intensities due to thermal quenching at increasing temperatures, which leads to reduced accuracy as the piston approaches top dead center. Thermographic measurements were successful to visualize local temperature changes due to evaporative cooling after fuel injection. The measured mean gas temperatures agreed well with zero-dimensional simulations that use additional wall-temperature measurements from thermographic phosphor measurements based on the lifetime method as input for heat transfer calculations.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) have a chance of long-term survival and potential cure after hepatic metastasectomy. However, the appropriate postoperative treatment strategy is still controversial. The CELIM and FIRE-3 studies demonstrated that secondary hepatic resection significantly improved overall survival. The objective of this analysis was to compare these favorable outcome data with recent results from the LICC trial investigating the antigen-specific cancer vaccine tecemotide (L-BLP-25) as adjuvant therapy in mCRC patients with LLD after R0/R1 resection. Data from mCRC patients with LLD and secondary hepatic resection from each study were analyzed for efficacy outcomes based on patient characteristics, treatment and surveillance after surgery. In LICC, 40/121 (33%) patients, in CELIM 36/111 (32%) and in FIRE-3-LLD 29/133 (22%) patients were secondarily resected, respectively. Of those, 31 (77.5%) patients in LICC and all patients in CELIM were R0 resected. Median disease-free survival after resection was 8.9 months in LICC, 9.9 months in CELIM. Median overall survival in secondarily resected patients was 66.1 months in LICC, 53.9 months in CELIM and 56.2 months in FIRE-3-LLD. Median age was about 5 years less in LICC compared to CELIM and FIRE-3. Secondarily resected patients of LICC, CELIM and FIRE-3 showed an impressive median survival with a tendency for improved survival for patients in the LICC trial. A younger patient cohort but also more selective surgery, improved resection techniques, deep responses and a close surveillance program after surgery in the LICC trial may have had a positive impact on survival. This article is protected by copyright. All rights reserved.

As part of the EUREC4A (Elucidating the role of cloud–circulation coupling in climate) field campaign, the German research aircraft HALO (High Altitude and Long Range Research Aircraft), configured as a cloud observatory, conducted 15 research flights in the trade-wind region east of Barbados in January and February 2020. Narrative text, aircraft state data, and metadata describing HALO's operation during the campaign are provided. Each HALO research flight is segmented by timestamp intervals into standard elements to aid the consistent analysis of the flight data. Photographs from HALO's cabin and animated satellite images synchronized with flight tracks are provided to visually document flight conditions. As a comprehensive product from the remote sensing observations, a multi-sensor cloud mask product is derived and quantifies the incidence of clouds observed during the flights. In addition, to lower the threshold for new users of HALO's data, a collection of use cases is compiled into an online book, How to EUREC4A, included as an asset with this paper. This online book provides easy access to most of EUREC4A's HALO data through an intake catalogue. Code and data are freely available at the locations specified in Table 6.

OBJECTIVE: Patients with Alzheimer disease dementia (ADD) often show impaired orientation and navigation. Signage offers an opportunity to compensate for these deficits, communicate information efficiently and facilitate wayfinding. Certain properties of signs such as colors and contrasts may beneficially affect the uptake and processing of information particularly in ADD patients.; METHODS: Thirty-six healthy older adults and 30 ADD patients performed a computerized color perception task that required discriminating different color combinations. The effects of different contrast features on performance accuracy and speed in the 2 experimental groups were examined by nonparametric mixed analysis of variances.; RESULTS: Analyses revealed a significant effect of contrast polarity on reaction times, significant effects of group on reaction times and errors as well as a marginally significant interaction of group*color on errors. All participants benefitted from positive contrast polarity (ie, dark target on lighter background) as indicated by increased performance speed. Furthermore, ADD patients reacted slower and less accurate than healthy controls, but showed higher accuracy at black-white and red-yellow than at blue-green color combinations.; CONCLUSIONS: Our findings suggest the implementation of signs with positive contrast polarity to ensure faster reactions. In addition, certain color combinations may enhance accuracy, particularly in patients with ADD. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

ZusammenfassungDieser Artikel bietet eine Übersicht über verfügbare invasive und nicht invasive Lungenfunktionstests bei Katzen. Die invasiven Techniken umfassen die arterielle Blutgasanalyse sowie die Messung der Lungenmechanik. Zu den nicht invasiven Methoden gehören neben der Pulsoxymetrie und Kapnografie auch bisher nicht in den Praxisalltag integrierte Methoden wie tidale Atemfluss-Volumen-Schleifen, barometrische Ganzkörperple-thysmografie und Thoraxkompression. In diesem Artikel werden Hintergründe, Durchführung, Interpretation und Limitationen der einzelnen Tests diskutiert. Bei korrekter Durchführung und Beurteilung der Befunde ermöglichen Lungenfunktionsmessungen, die Pathophysiologie von Atemwegserkrankungen bei Katzen besser zu verstehen und die vorliegende Erkrankung sowie Wirksamkeit einer Therapie objektiver einzuschätzen.

Conduction disturbances after transcatheter aortic valve implantation (TAVI) are common, heterogeneous, and frequently result in permanent pacemaker implantation (PPI). Pacemaker therapy with a high rate of right ventricular pacing is associated with heart failure, hospitalizations, and reduced quality of life.The purpose of this study was to compare medium-term outcomes between PPI implantation strategies, as choosing the right indication for PPI is still an area of uncertainty and information on outcomes of PPI regimens beyond 1 year is rare.We compared outcomes after 3 years between a restrictive PPI strategy, in which the lowest threshold for PPI was left bundle branch block (LBBB) (QRS120 ms) with the presence of new atrioventricular block (PQ200 ms), and a liberal PPI regimen, in which PPI already was performed in patients with new-onset LBBB.Between January 2014 and December 2016, TAVI was performed in 884 patients at our center. Of these, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs 38.1%; P.001). The incidence of the primary endpoint (all-cause-mortality and hospitalization for heart failure) after 3 years was similar in both groups (30.7% vs 35.2%; P = .242), as was all-cause-mortality (26.6% vs 29.2%; P = .718). Overall, patients who required PPI post-TAVI had significantly more hospitalizations due to heart failure (14.8% vs 7.8%; P = .004).A restrictive PPI strategy after TAVI reduces PPI significantly and is safe in medium-term follow-up over 3 years.

Mitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now.We enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010-03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p 0.001) at 30 days and in 36.6% (p 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53-5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29-2.94], p = 0.001) independently in both etiologies of MR.TMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.

Dust emissions during storage of non-moving bulk materials are studied with a numerical method. The model relies on a contact-model-free Discrete Element Method (DEM) to model the bulk particle–fluid interaction and the dust removal coupled with Computational Fluid Dynamics (CFD) to model the gas and the dust phase in a multiphase framework. Here, two storage scenarios are considered: a flown through packed bed and a flown over stockpile. For the first, the performed simulations reveal that the dust discharge can be correlated with the passing fluid pressure drop. For the second, a parameter study of factors influencing the dust emissions is performed. The parameters discussed are the stockpile size, the gas velocity, the slope angle, the particle diameter and the shape of the stockpile, taking into account conical and truncated conical stockpiles. Dust release correlations are obtained for both scenarios, which reflect very well the obtained numerical results.

Slow periodic myoclonus is a well-recognized phenotype of fulminant subacute sclerosing panencephalitis (video 1).1 This distinctive phenotype has not been previously recognized in another rapidly progressive disorder, fulminant Wilson disease. We documented slow periodic myoclonus in a 34-year-old Peruvian man who developed paranoid schizophrenia and, 6 months later, levodopa-unresponsive parkinsonism and falls, progressing into akinetic mutism (video 2). Prior to death, the diagnosis of Wilson disease was supported by ocular and neuroimaging features (figure), low ceruloplasmin (5.3 U/L), high urinary copper, and diffuse hepatopathy on echography. Slow periodic flexor myoclonus reflects cortical excitability and bears a poor prognosis.2 The EEG correlates are generalized, high-amplitude, quasiperiodic complexes.

In the context of black soldier fly (BSF) rearing, often the residues from production — mainly faeces but also undigested substrate — are addressed as frass in a broader sense. As BSF production is expanding, the valorization of BSF frass as organic fertilizer is gaining importance. However, in contrast to established organic fertilizers, little is known on the properties and variation of this by-product, which is essential for assessing possible application purposes. To elaborate a first overview on this relatively new waste stream, BSF frass analyses from the literature and anonymized frass analyses enquired from BSF producers were compiled. For a possible agricultural use as a fertilizer, their nutrient patterns were assessed. With a balanced nitrogen:phosphorous pentoxide:potassium oxide (N:P2O5:K2O) ratio of 1:0.9:1.1, BSF frass can be characterized as a slightly alkaline (pH 7.5), nutrient-rich compound fertilizer, with the nutrient and especially the micronutrient contents showing high variation. The comparably high carbon-to-nitrogen ratio and low shares of ammonium nitrogen indicate a limited immediate nutrient release and point to possible applications of frass as a long-term fertilizer. The use of frass as an organic fertilizer as one element in a fertilization strategy is promising. By improving nutrient cycling back to the field, BSF frass can represent an important element of sustainable circular agriculture. However, more information on BSF feed and production systems needs to be combined with the nutrient analyses to better understand the variation in frass nutrient contents.

Background In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected. Objective This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany. Material and methods As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women. Results A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection. Conclusion The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients.

The high morbidity following surgical interventions on the chest wall because of large incisions often prevents surgeons from operative rib fracture treatment. Minimally invasive approaches to the intrathoracic side of the rib could allow for smaller incisions with lower morbidity while maintaining stability of fixation. The aim of this study was to explore the biomechanical competence of intrathoracic versus extrathoracic plating in a human cadaveric rib fracture model and investigate the effect of plating using two versus three screws per fracture fragment.Twenty pairs of fresh-frozen human cadaveric ribs from elderly female donors aged 82.4 ± 7.8 years were used. First, the stiffness of each native rib was calculated via nondestructive (2 N-5 N) biomechanical testing under two loading conditions: ramped two-point bending and combined ramped tensile bending with torsional loading. Second, the ribs were fractured under three-point bending with their intrathoracic side put under tensile stress. Third, specimens were assigned to four groups (n = 10) for either intrathoracic or extrathoracic plating with two or three screws per fragment. Following instrumentation, all ribs were dynamically tested over 400,000 cycles under combined sinusoidal tensile bending with torsional loading (2 N-5 N at 3 Hz). Finally, all specimens were destructively tested under ramped two-point bending.Following instrumentation and cyclic testing, significantly higher construct stiffness was observed for intrathoracic vs. extrathoracic plating under anatomical loading conditions (p ≤ 0.03). No significant differences were detected for implant subsidence after plating with two or three screws per fragment (p ≥ 0.20).This study demonstrates significantly higher construct stiffness following intrathoracic over extrathoracic plating, thus indicating superior plate support of the former. In the clinical context, using only two instead of three screws per fragment not only could maintain stability of fixation but also decrease surgery time and costs, and allow for smaller incisions with lower morbidity.Therapeutic/Care Management; Level V.

The integration of carbon nanotube fabric into textiles is paving its way into smart materials and wearable applications. Potential novel applications of carbon nanotube hybrid (CNTH) materials and fabric composites span across a range of market levels from high-level PPE appropriate for military and industrial applications down to consumer products that can be used in everyday scenarios. The high-level performance properties of CNTH materials and their ability to be customized provide new possibilities for constructing fabrics with properties that are made to order. Furthermore, CNTH in combination with advanced textile compositing and construction methods allows the CNTH material to further leverage material customization aspects to meet specific requirements. The unique synthesis process for nanotube fabric allows for modification of the physical properties of the CNTH itself. The CNTH fabric combined with the customizability of standard textile composite materials and with the use of apparel design features allows for the design of materials with new combinations of physical properties. These unique properties offer high potential for developing families of smart wearable garments that can be scaled for industrial production. This article discusses the synthesis of carbon nanotube hybrid fabric, the process of hybrid fabric and textile integration, properties of the hybrid textile, and potential applications. The paper also provides an outlook towards large scale production of the hybrid textile material.

Objectives The aims of this study were to determine if there was an increased risk of incident cardiovascular disease (CVD) and diabetes and an increase in arterial stiffness in participants who reported working 41–54 h per week and more than 55 h compared to those who worked 40 h or less over a time interval of 5 years. Methods In a subsample of the population-based prospective Gutenberg Health Study (GHS) study, we examined working participants younger than 65 years at baseline (n = 7241) and after 5 years. To test the association of working time at baseline and incident cardiovascular events and diabetes type II, we estimated hazard ratios (HR) using competing risks models. For a change in the arterial stiffness index (SI) based on assessment using a Pulse Trace PCA2 device, we used multivariate linear regression models. Results The SI increased in those working more than 55 h per week (beta coefficiant = 0.32 m/s (95% CI 0.07–0.58) compared to those working 40 h and less after adjustment for sex, age and SES. Due to small numbers there was no significant association of working hours and clinically manifest cardiovascular events and diabetes type II in the 5-year follow-up time. Conclusions Further studies are needed to confirm the results on working hours and arterial stiffness. Analyses of the 10-year follow-up with more events may clarify the results for incident cardiovascular events and metabolic outcomes.

Purpose Even though obesity is a known risk factor for needing cholecystectomy, most research excludes patients with higher degrees of obesity. The aim of this retrospective study was to compare postoperative pain and analgesic consumption in obese patients, who underwent either transvaginal hybrid Natural Orifice Transluminal Endoscopic Surgery (NOTES) cholecystectomy (NC) or traditional laparoscopic cholecystectomy (LC). Methods Between 12/2008 and 01/2017, 237 NC were performed, of which 35 (14.8%) showed a body mass index (BMI) of 35 kg/m2 or more (obesity II and III according to the World Health Organization). Of these, procedural time, postoperative pain, analgesic requirements, and other early postoperative parameters were collected and compared with 35 matched LC patients from the same time period. Results There were no differences in the baseline characteristics between the two groups, but we found significant benefits for the hybrid NOTES technique in terms of less pain (P = 0.006), coherent with significantly less intake of peripheral (paracetamol; P = 0.005), and of centrally acting analgesics (piritramide; P = 0.047) within the first two-day post-surgery. We also found that those in the NC group had shorter hospital stays (P Conclusion With regard to postoperative pain and analgesic requirements and without an increase in postoperative complications, obese patients experience short-term benefits from the hybrid NOTES technique compared to traditional laparoscopic cholecystectomy.

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N - and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved ‘high-coverage’ and ‘high-accuracy’ glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics., This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.

Objectives This study sought to identify predictors of major clinically important atrial fibrillation endpoints in hypertrophic cardiomyopathy. Background Atrial fibrillation (AF) is a common morbidity associated with hypertrophic cardiomyopathy (HCM). The HCMR (Hypertrophic Cardiomyopathy Registry) trial is a prospective natural history study of 2,755 patients with HCM with comprehensive phenotyping. Methods All patients received yearly telephone follow-up. Major AF endpoints were defined as requiring electrical cardioversion, catheter ablation, hospitalization for >24 h, or clinical decisions to accept permanent AF. Penalized regression via elastic-net methodology identified the most important predictors of major AF endpoints from 46 variables. This was applied to 10 datasets, and the variables were ranked. Predictors that appeared in all 10 sets were then used in a Cox model for competing risks and analyzed as time to first event. Results Data from 2,631 (95.5%) patients were available for analysis after exclusions. A total of 127 major AF endpoints events occurred in 96 patients over 33.3 ± 12.4 months. In the final model, age, body mass index (BMI), left atrial (LA) volume index, LA contractile percent (active contraction), moderate or severe mitral regurgitation (MR), and history of arrhythmia the most important. BMI, LA volume index, and LA contractile percent were age-dependent. Obesity was a stronger risk factor in younger patients. Increased LA volume, reduced LA contractile percent, and moderate or severe MR put middle-aged and older adult patients at increased risk. Conclusions The major predictors of major AF endpoints in HCM include older age, high BMI, moderate or severe MR, history of arrhythmia, increased LA volume, and reduced LA contractile percent. Prospective testing of a risk score based on these parameters may be warranted.

Lukas Rath, Friedrich Jokisch, Gerald Bastian Schulz, Alexander Kretschmer, Alexander Buchner, Christian G Stief, Philipp Weinhold Department of Urology, Ludwig-Maximilians-University, Munich, GermanyCorrespondence: Philipp WeinholdDepartment of Urology, Ludwig-Maximilians-University, Marchioninistrasse 15, Munich, 81377, GermanyTel +4989-4400-73528Fax +49894400-78735Email philipp.weinhold@med.uni-muenchen.dePurpose: There are only a few case reports and case series that investigated combined laparoscopic or robotic surgery for simultaneous prostate and kidney cancer. In this study, we want to close a gap in existing research to assess the feasibility and oncological outcome of combined open prostatectomy and kidney surgery.Methods: We retrospectively analyzed patients who underwent a combined open prostatectomy and either a partial or complete nephrectomy from 2013 to 2020. Descriptive statistics were used to assess perioperative parameters and the 12-month functional and oncological outcomes after combined surgery.Results: We identified 10 patients undergoing combined open surgery. Partial nephrectomy was performed in 4, radical nephrectomy in 6 patients. For prostate cancer, histopathological analysis showed a tumor stage ≥ pT2c in all 10 patients. For renal tumors, histopathological analysis showed clear cell renal cell carcinoma in 8 patients and oncocytoma in 2 patients. Operating time was 177 ± 36 minutes. Two perioperative complications (Clavien 2a and 3) were observed. Three months postoperatively, the International Index of Erectile Function (IIEF-5) score was 5.6 ± 5.9, the ICIQ-SF score was 7.3 ± 5.6 and were using 1.9 ± 2.2 pads per day. This improved after 12 months postoperatively, as patients had an IIEF-5 score of 6.33 ± 6.5, an ICIQ-SF score of 4.4 ± 5.7 and were using pads 0.9 ± 1.7 per day.Conclusion: In this study, we showed that open surgery is a safe and valid approach for combined prostatectomy and renal surgery with acceptable complications and oncological outcomes. The combined open approach could be a good alternative to combined laparoscopic/robotic surgery in this field, especially to treat patients with advanced renal tumors or previous abdominal surgery or radiation.Keywords: retropubic prostatectomy, kidney surgery, simultaneous prostate and kidney cancer, combined surgery

Objective Development and psychometric evaluation of a multidimensional model and assessment scales measuring core aspects of the quality of woman-centred midwifery care processes in Germany. Design & Participants 201 women, who received midwifery care during their pregnancy in 2018, were enrolled 6 to 18 months after birth. Data were assessed in a retrospective cross-sectional survey in Germany. Measurements Established scales that are used in health care were adapted to the context of woman-centred midwifery care: Shared Decision-Making (SDM-Q-9-M), Empathy (CARE-M), Internal Team Participation (TEAM-M) and Professional Competence (PC-M). Confirmatory factor analyses were adapted to prove (a) the homogeneity of the single scales and (b) the multidimensional structure of the entire item pool. Findings Appropriate to good model fit was confirmed for both the single assessments (CFI ≥ .96; SRMR ≤ .032) and the multidimensional model (CFI = .96; SRMR = .049). Minor model modifications reflecting local item dependencies had to be considered for the scales SDM-Q-9-M, TEAM-M, and PC-M. For the CARE-M scale, Participatory Communication proved to be a separate, second structural component. Conclusions Shared Decision-Making, Empathy, Internal Team Participation, and Professional Competence constitute core components of woman-centred midwifery care processes. A multi-dimensional assessment is now available measuring women's experiences with midwifery care. The assessment provides an essential component to master the complex challenge of measuring the quality of midwifery care inside and outside the hospital by means of a standardised and validated assessment.

DNA damage is a constant event in every cell caused by exogenous factors such as ultraviolet and ionizing radiation (UVR/IR) and intercalating drugs, or endogenous metabolic and replicative stress. Proteins of the DNA damage response (DDR) network sense DNA lesions and induce cell cycle arrest, DNA repair, and apoptosis. Genetic defects of DDR or DNA repair proteins can be associated with immunodeficiency, bone marrow failure syndromes, and cancer susceptibility. Although various diagnostic tools are available to evaluate DNA damage, their quality to identify DNA repair deficiencies differs enormously and depends on affected pathways. In this study, we investigated the DDR biomarkers γH2AX (Ser139), p-ATM (Ser1981), and p-CHK2 (Thr68) using flow cytometry on peripheral blood cells obtained from patients with combined immunodeficiencies due to non-homologous end-joining (NHEJ) defects and ataxia telangiectasia (AT) in response to low-dose IR. Significantly reduced induction of all three markers was observed in AT patients compared to controls. However, delayed downregulation of γH2AX was found in patients with NHEJ defects. In contrast to previous reports of DDR in cellular models, these biomarkers were not sensitive enough to identify ARTEMIS deficiency with sufficient reliability. In summary, DDR biomarkers are suitable for diagnosing NHEJ defects and AT, which can be useful in neonates with abnormal TREC levels (T cell receptor excision circles) identified by newborn screening. We conclude that DDR biomarkers have benefits and some limitations depending on the underlying DNA repair deficiency., publishedVersion

The COVID-19 pandemic has greatly changed the utilization of ambulatory medical care. Studies indicate that this also includes a decrease in pediatric prevention services.The aim of the study was to determine how the utilization of pediatric prevention services, in particular screening examinations and immunizations, developed over the course of the first pandemic wave until the end of September 2020 compared with the years 2015 to 2019.A data analysis based on nationwide statutory medical claims data from the first quarter of 2015 to the third quarter of 2020 was conducted. All treatments of patients aged 0 to 17 years were included and the quarterly case numbers compared on an annual basis. By considering trends and seasonality, preventive and curative treatment cases were modelled as a time series and compared to their expected values.No decreases in the quarterly numbers of screening examinations or immunizations were observed in 2020. In contrast, the number of curative pediatric cases decreased significantly in the second and third quarters of 2020 compared with the same periods of the previous years. Since there was no drop in the number of screening examinations, it should be assumed that the health problems addressed in this framework are detected in a timely manner despite the COVID-19 pandemic. However, since screenings do not cover all age groups, further investigation should be conducted to determine the health consequences of the observed decrease in curative cases.HINTERGRUND: Die COVID-19-Pandemie hat die Inanspruchnahme der vertragsärztlichen Versorgung stark verändert. Untersuchungen geben Hinweise darauf, dass es dabei auch zu Einbrüchen bei kinderärztlichen Präventionsleistungen gekommen ist.Ziel der Studie war es zu ermitteln, wie sich die Inanspruchnahme der kinder- und jugendärztlichen Versorgung, insbesondere von Früherkennungsuntersuchungen und Impfungen, im Verlauf der ersten Pandemiewelle bis Ende September 2020 im Vergleich zu den Jahren 2015 bis 2019 entwickelt hat.Anhand bundesweiter vertragsärztlicher Abrechnungsdaten wurde eine Sekundärdatenanalyse für den Zeitraum erstes Quartal 2015 bis drittes Quartal 2020 durchgeführt. Pro Beobachtungsjahr wurden alle kinder- und jugendärztlichen Behandlungsfälle im Alter von 0 bis 17 Jahren eingeschlossen und die quartalsbezogenen Fallzahlen jahresweise gegenübergestellt. Präventive und kurative Behandlungsfälle wurden als Zeitreihen modelliert und unter Berücksichtigung von Trends und Saisonalität ihren Erwartungswerten gegenübergestellt.Weder bei den Früherkennungsuntersuchungen noch bei den Impfungen war auf der Quartalsebene ein Rückgang der Fallzahlen für 2020 zu erkennen. Demgegenüber sank die Zahl der kurativen Fälle im zweiten und dritten Quartal deutlich gegenüber den Vorjahreszeiträumen. Aufgrund des ausbleibenden Fallzahlrückgangs bei den Früherkennungsuntersuchungen sollte davon ausgegangen werden, dass die in diesem Rahmen adressierten Gesundheitsprobleme auch während der COVID-19-Pandemie rechtzeitig erkannt werden. Da die Früherkennungsuntersuchungen jedoch nicht alle Altersgruppen abdecken, sollte weiter untersucht werden, welche gesundheitlichen Folgen der beobachtete Rückgang bei den kurativen Fällen nach sich zieht.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer arising from lymphoblasts of T-cell origin. While TALL accounts for only 15% of childhood and 25% of adult ALL, 30% of patients relapse with a poor outcome. Targeted therapy of resistant and high-risk pediatric T-ALL is therefore urgently needed, together with precision medicine tools allowing the testing of efficacy in patient samples. Furthermore, leukemic cell heterogeneity requires drug response assessment at the single-cell level. Here we used single-cell mass cytometry to study signal transduction pathways such as JAK-STAT, PI3K-AKT-mTOR and MEK-ERK in 16 diagnostic and five relapsed T-ALL primary samples, and investigated the in vitro response of cells to Interleukin-7 (IL-7) and the inhibitor BEZ-235. T-ALL cells showed upregulated activity of the PI3K-AKT-mTOR and MEK-ERK pathways and increased expression of proliferation and translation markers. We found that perturbation induced by the ex vivo administration of either IL-7 or BEZ-235 reveals a high degree of exclusivity with respect to the phospho-protein responsiveness to these agents. Notably, these response signatures were maintained from diagnosis to relapse in individual patients. In conclusion, we demonstrated the power of mass cytometry single-cell profiling of signal transduction pathways in T-ALL. Taking advantage of this advanced approach, we were able to identify distinct clusters with different responsiveness to IL-7 and BEZ-235 that can persist at relapse. Collectively our observations can contribute to a better understanding of the complex signaling network governing T-ALL behavior and its correlation with influence on the response to therapy.

Aims Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Methods and results Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6–37.4%], 13.3% [12.6–13.9%], and 40.8% [39.9–41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19–1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11–2.05), P = 0.009]. Conclusion Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.

Tumor microenvironment-targeted therapies are emerging as promising treatment options for different cancer types. Tumor-associated macrophages and microglia (TAMs) represent an abundant nonmalignant cell type in brain metastases and have been proposed to modulate metastatic colonization and outgrowth. Here we demonstrate that targeting TAMs at distinct stages of the metastatic cascade using an inhibitor of colony-stimulating factor 1 receptor (CSF1R), BLZ945, in murine breast-to-brain metastasis models leads to antitumor responses in prevention and intervention preclinical trials. However, in established brain metastases, compensatory CSF2Rb–STAT5-mediated pro-inflammatory TAM activation blunted the ultimate efficacy of CSF1R inhibition by inducing neuroinflammation gene signatures in association with wound repair responses that fostered tumor recurrence. Consequently, blockade of CSF1R combined with inhibition of STAT5 signaling via AC4-130 led to sustained tumor control, a normalization of microglial activation states and amelioration of neuronal damage. Klemm et al. show that resistance to CSF1R inhibition in breast cancer brain metastasis is driven by compensatory activation of the CSF2Rb–STAT5 axis in macrophages, which can be alleviated by combined targeting of CSF1R and STAT5.

Introduction: Breast cancer can be a major challenge for those affected. Knowledge of changes in fine motor dexterity in affected women due to routine cancer therapies can help guide effective support. Methods: For this prospective observational study, we collected data of 79 women with a mean age 54.6 ± 9.5 years prior to, after breast cancer therapy (T1), and at 3-month follow-up. The fine motor dexterity was assessed for 4 treatment subgroups: SC = Surgery + Chemotherapy, SCR = Surgery + Chemotherapy + Radiotherapy Therapy, SR = Surgery + Radiotherapy, and S = Surgery. Results: Over time, women with breast cancer showed significant decreases in fine motor dexterity across all treatment groups (p < 0.001). The strongest negative effect was seen in the treatment groups receiving additional chemotherapy. SCR group showed pronounced limitations for dominant hand (DH) −12%; non-dominant hand (NDH) −15%; both hands (BH) −17%; assembly (ASSY) −11% at T1. Significant interaction was noticeable in DH (F = 5.59, p < 0.001), NDH (F = 6.61, p < 0.001), BH (F = 13.11 p < 0.001), and ASSY (F = 5.84 p < 0.001). Discussion/Conclusion: Our study showed that the extent of change in fine motor dexterity depends on the treatment regimen. The detection of unmet care needs could help to personalize and optimize clinical and survivorship care. Based on our findings, multidisciplinary support initiated early in breast cancer therapy is required.

Purpose Colorectal cancer and its treatment are associated with debilitating side effects. Exercise may improve the physical and psychological wellbeing of cancer patients; however, evidence in colorectal cancer patients undergoing adjuvant chemotherapy is limited. This pilot study aimed to explore the effects of supervised aerobic exercise on cardiorespiratory fitness and patient-reported health outcomes in colorectal cancer patients undergoing adjuvant chemotherapy. Methods Patients who had undergone curative resection for colorectal cancer (stages II–III) and were scheduled to receive adjuvant chemotherapy were enrolled into this non-randomized controlled trial. Patients in the intervention group (IG) took part in a 6-month supervised aerobic exercise program, while the control group (CG) received usual care. Cardiorespiratory fitness (measured by peak oxygen consumption) was assessed at baseline and 6 months. Fatigue, quality of life, and physical activity levels were additionally assessed at 3 months. Results In total, 59 patients (33 in IG vs. 26 in CG) were enrolled into this study. Eighteen patients (9 in IG vs. 9 in CG) dropped out of the study prior to the 6-month follow-up. Significant improvements in cardiorespiratory fitness (p = .002) and selected patient-reported health outcomes, such as reduced motivation (p = .015) and mental fatigue (p = .018), were observed in the IG when compared to the CG. Conclusion To our knowledge, this is the first study to investigate the effects of a supervised aerobic exercise program in colorectal cancer patients undergoing adjuvant chemotherapy. The significant and clinically meaningful improvements in CRF warrant further randomized controlled trials to confirm these findings. Trials registration German Clinical Trials Register Identifier: DRKS00005793, 11/03/2014, retrospectively registered.