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Dank optimierter chirurgischer und multimodaler Therapiekonzepte konnte die Prognose beim Rektumkarzinom uber die vergangenen Jahrzehnte stark verbessert werden. Lesen Sie im Folgenden, was sich im Hinblick auf Diagnostik, Chirurgie und (Neo-)Adjuvanz getan hat. Diskutiert werden zudem der Watch-and-Wait-Ansatz nach kompletter Remission und Masnahmen zur Senkung der Anastomoseninsuffizienzrate.

INTRODUCTIONThe objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD IgG response over time among older people after COVID-19 infection or vaccination and its comparison with speculative levels of protection assumed by current data.METHODSFrom November 2020 to October 2021, we included geriatric patients with serological test results for COVID-19.We considered antibody titre thresholds thought to be high enough to protect against SARS-CoV-2 infection: 141 BAU/ml for protection/vaccine efficacy > 89.3%.Three cohorts are presented. A vaccine group (n=34) that received two BNT162b2/Comirnaty injections 21 days apart, a group of natural COVID-19 infection (n=32) and a third group who contracted COVID-19 less than 15 days after the first BNT162b2/Comirnaty injection (n=17).RESULTS83 patients were included, the median age was 87 (81-91) years.In the vaccine group at 1 month since the first vaccination, the median BAU/ml with IQR was 620 (217-1874) with 87% of patients above the threshold of 141 BAU/ml. Seven months after the first vaccination the BAU/ml was 30 (19-58) with 9.5% of patients above the threshold of 141 BAU/ml.In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median BAU/ml was 798 (325-1320) with 86.7% of patients above the threshold of 141 BAU/ml and fell to 88 (37-385) with 42.9% of patients above the threshold of 141 BAU/ml at 2 months. The natural infection group was vaccinated three months after the infection. Five months after the end of the vaccination cycle the BAU/ml was 2048 (471-4386) with 83.3% of patients above the threshold of 141 BAU/ml.DISCUSSIONOn the humoral level, this supports the clinical results describing the decrease in vaccine protection over time.

Background Anastomotic leakage (AL) is a major complication after esophagectomy, potentiating morbidity and mortality. There are several patient risk factors associated with AL, but high-fidelity postoperative predictors are still under debate. The aim was to identify novel reliable predictors for AL after esophagectomy. Methods A high-volume single-center database study, including 138 patients receiving Ivor-Lewis-esophagectomy between 2017 and 2019, was performed. Serum levels of albumin, aPTT, and lactate before and after surgery were extracted to assess their impact on AL and in-hospital mortality. Results High serum lactate on postoperative day 1 (POD1) could be shown to predict AL after esophagectomy [AL vs. no AL: 1.2 (0.38) vs. 1.0 (0.37); p p p = 0.018]. Further, low serum albumin on POD0 [2.6 (0.53) vs. 3.1 (0.56); p = 0.001] and high serum lactate on POD 0–1 [1.1 (0.29) vs. 0.9 (0.30); p = 0.043] were associated with in-hospital death. Strikingly, logistic-regression (HR: 0.111; p = 0.008) and cox-regression analysis (HR: 0.118; p = 0.003) showed low serum albumin as an independently predictor for in-hospital death after esophagectomy. Conclusions This study identified high serum lactate as an independent predictor of AL and low serum albumin as a high-fidelity predictor of in-hospital death after esophagectomy. These parameters can facilitate improved postoperative treatment leading to better short-term as well as long-term outcomes.

Purpose The SARS-CoV-2 pandemic has almost stopped all elective surgical treatment throughout the world. As operating room (OR) capacities are reduced everywhere to ensure availability of intensive care capacities, especially low-complex surgical procedures are often postponed. These include totally implantable central-venous access ports which are important for the oncologic treatment of cancer patients. Methods In our study, we investigated the potential of an outpatient surgical centre (OSC) in terms of workflow effectiveness compared to the central operating room complex (COR) of a university hospital using low-complex surgical procedures as an example. Data of 524 consecutive patients who received a Port-a-cath procedure (422 implantations (80.5%) and 102 explantations (19.5%)) in our department between February 2019 and February 2020 were evaluated. Results A total of 277 patients were operated in outpatient surgical centre (OSC), and 247 patients received the procedure in the central OR (COR) complex. Grade II and III complications according to the Clavien–Dindo classification occurred in 5.2% (OSC) and 7.3% (COR) of patients. Incision-to-suture time was significantly quicker in the OSC group (36 vs. 42 min., p p Conclusion In order to ensure effective OR utilization especially in times of the corona pandemic, the use of smaller decentralized OR units, e.g., outpatient surgical centres, for performing low-complex surgical cases is beneficial. Our study revealed shorter total OR and preparation-to-incision times.

Several studies have already explored individual and environmental risk factors for COVID-19 morality, however most study populations consisted of the overall population and mainly from China or the US. Our study focused on COVID-19 mortality in the elderly in seven European cities. Long-term exposure to air pollution was estimated through annual pollutant concentrations at the residential address averaged over the last two years of the study period between February and May 2020. We focused on the main outdoor air pollutants PM10, PM2.5, NO2 and O3. Short-term variations in air pollutants and weather parameters (e.g. temperature, UV, relative humidity) were also examined through a 20-day period before the confirmed PCR diagnostic of COVID-19. Individual risk factors such as smoking status, sex, body mass index (BMI), ischemic heart disease, diabetes, hypertension, chronic renal failure, history of cancer, COPD, and lung fibrosis, were taken into account. We found positive associations for diabetes and COVID-19 mortality (OR 2.2 CI 95% :1.1, 4.4). Using a multivariate logistic regression model adjusted for all patient characteristics and city, we fail to reject the null hypothesis of no association between COVID-19 mortality and long-term and short-term increase in PM2.5, PM10, NO2 and O3. Our study suffers from the fact that patient profiles strongly differ between high-polluted and less-polluted cities. Strong differences in COVID-19 mortalities were observed between cities, which could be due to differences in COVID-19 management and treatment, such as accessibility to reanimation and intensive units between cities. Overall, our study highlights the need to improve estimation of individual exposure to air pollution. Indeed, even with the high-efficiency modelisation systems used in our study, we were unable to estimate the effect of air pollution within each city, because variations in air pollution exposure were too small. Individual markers of air pollution exposure such as recently demonstrated with urinary black carbon or passive individual samplers, would be most suitable for future explorations. Concerning weather parameters, although previous studies concluded that increase in temperature and UV index could decrease COVID-19 morality, our data did not allow us to reject the null hypotheses.

BACKGROUND Animal-assisted interventions (AAI) show promising results but they suffer from a lack studies and contradictory results. OBJECTIVE Our study deals with dog intervention and agitation in older patients with dementia. METHODS An epidemiological quasi-experimental study was carried out in patients living in a Special Care Unit (SCU) of an Ehpad in the French Region of Haut-Rhin. Agitation was assessed by the Cohen-Mansfield Agitation Inventory at three consecutive periods of one month after the instauration, discontinuation and resumption of a dog mediation. RESULTS 26 patients were included in the study (76,92% female); mean age was 85,35 years and the mean score on MMSE was 6,85. Stopping AAI leads to a 11,9% relative increase in agitation (p = 0,03) whereas reintroduction of AAI leads to a 29,9% relative decrease in agitation (p

Context: The complexity of modern safety-critical systems in industries keep on increasing due to the rising number of features and functionalities. This calls for formal methods in order to entrust confidence in such systems. Nevertheless, using formal methods in industry is demanding because of usability issues, e.g., the difficulty of understanding model checking results. Thus the hypothesis is, presenting the result of model checker results in a user-friendly manner could promote formal methods usage in industries. Objective: We aim to evaluate the acceptance of formal methods by engineers if the complexity of understanding verification results is made easy. Method: We perform two different exploratory studies. First, we conduct an online survey to explore challenges in identifying inconsistent specifications and using formal methods from engineers. Second, we perform a one group pretest and posttest experiment to collect impressions from engineers using formal methods if understanding verification results is eased. Limitations: The main limitation of this study is the generalization because the survey focuses on a particular target group and it uses a pre-experimental design., 7 pages, 1 figure, 3 tables. This papers is accepted as Registered Reports Track in ICSME 2021

The acoustic emission (AE) technique has been successfully used for decades to monitor fracture processes during laboratory testing. This final chapter discusses deliberations necessary when the technique is employed under the often harsh practical conditions that exist on real structures and the application of AE techniques is thus more challenging. As a result, many statements are on the more cautious side and less enthusiastic than what they might be coming from an optimistic perspective of a basic researcher or a system developer. Nevertheless, the authors believe that testing and monitoring approaches based on the AE technique provide significant benefits for both condition assessment and structural health monitoring (SHM) of structures not only in the laboratory but also on real structures, if employed appropriately. One main aspect of AE monitoring is the choice of the analysis technique to be utilized. Some approaches may work with data from only a few sensors and are thus computationally efficient and simple to apply. However, those typically allow only for qualitative assessments. In contrast, approaches that might provide detailed quantitative information regarding the physics of AE events require extensive sensor networks, involve sophisticated computations, and might fail under harsh real-world conditions. To illustrate these points, select examples of AE monitoring studies on real structures are provided. These help to understand the value and limitations of various signal- and parameter-based AE techniques and serve as a basis for decisions about appropriate monitoring strategies. Site conditions, cost, safety, and other aspects are discussed as well, in an attempt to provide a potential user with practical advice on AE monitoring of large-scale and real structures with high noise levels and limited access. While most statements and recommendations are transferable, the focus of this chapter is on concrete structures.

Here, we present the case of an 81‐year‐old male patient, who was hospitalized for a severe form of COVID‐19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero‐basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero‐lateral LV walls, and sub‐epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post‐COVID‐19 active myocarditis.

With the increase of research in self-adaptive systems, there is a need to better understand the way research contributions are evaluated. Such insights will support researchers to better compare new findings when developing new knowledge for the community. However, so far there is no clear overview of how evaluations are performed in self-adaptive systems. To address this gap, we conduct a mapping study. The study focuses on experimental evaluations published in the last decade at the prime venue of research in software engineering for self-adaptive systems - the International Symposium on Software Engineering for Adaptive and Self-Managing Systems (SEAMS). Results point out that specifics of self-adaptive systems require special attention in the experimental process, including the distinction of the managing system (i.e., the target of evaluation) and the managed system, the presence of uncertainties that affect the system behavior and hence need to be taken into account in data analysis, and the potential of managed systems to be reused across experiments, beyond replications. To conclude, we offer a set of suggestions derived from our study that can be used as input to enhance future experiments in self-adaptive systems.

A human immunodeficiency virus (HIV) infection is no longer an absolute contraindication for solid organ transplantation, yet such a setting is still challenging and little explored because of general reservations and medical difficulties. We describe a 51-year-old man with end-stage renal failure due to polycystic kidney disease who underwent an ABO-incompatible kidney transplantation from his 49-year-old male partner. Early postoperative course revealed an episode of suspected acute rejection, which was successfully managed with a steroid pulse. Both donor and recipient continued to have an undetectable viral load after adjusting antiretroviral medication to renal function. To the best of our knowledge, this is the first report of a successful ABO-incompatible living donor kidney transplantation from an HIV-positive donor in an HIV-positive recipient, and this case seems to be a valuable approach with favorable results.

Background: Interval aerobic training programs with active recovery bouts (IATP-R) are reported as being more adapted to seniors while improving cardiorespiratory and endurance parameters. Report of benefits on vascular function is still limited. Purpose: To measure the impact of IATP-R on vascular function among seniors. Methods: Sedentary volunteers (≥70 years of age) were randomly assigned to either IATP-R (n = 30) or control group (n = 30). The IATP-R consisted of 2 weekly sessions of 30-min (6 × 4-min at first ventilatory threshold (VT1) intensity + 1-min at 40% of VT1) cycling exercise over 9.5-week. Controls remained their sedentary life over the same period. In all participants, the endothelial function was measured by flow-mediated dilation (FMD) in brachial artery and arterial stiffness through the carotid/radial and carotid/femoral pulse wave velocity (PWV). Systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and 9.5 weeks later. Results: Resulting from a planned interim analysis, IATP-R improved SBP (IATP-R: from 133.7 ± 9.8 to 122.6 ± 9.4 mmHg vs. Controls: from 128.9 ± 12.5 to 132.6 ± 14.7 mmHg), DBP (IATP-R: from 80.2 ± 7.0 to 74.1 ± 6.7 mmHg vs. Controls: from 77.1 ± 6.8 to 80.3 ± 7.5 mmHg), and FMD (IATP-R: from 6.7 ± 2.0 to 7.5 ± 2.7% vs. Controls: from 7.9 ± 2.7 to 7.5 ± 2.5%). No significant impact on PWV was measured. Conclusion: Although these findings resulted from an interim analysis, IATP-R might be effective in regulating BP and improving endothelial function among sedentary seniors.

Summary The objective of this narrative review was to provide an update on oral and nasal vitamin B12 (cobalamin) therapy in elderly patients. Relevant articles were identified by ‘PubMed’ and ‘Scholar Google’ search from January 2010 to July 2018 and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the ‘Cochrane Library’ and the ‘ISI Web of Knowledge’. Data retrieved from international meetings were also used, as was information retrieved from commercial sites on the web and data from ‘CARE B12’ research group. For oral vitamin B12 therapy, four prospective randomized controlled trials, eight prospective studies, one systematic and four reviews fulfilled our inclusion criteria. The studies included mainly or exclusively elderly patients (≥65-year-olds). In all of the studies, the mean age of the patients was at least 70 years except for two. The present review documents that oral vitamin B12 replacement at 1000 μg daily proved adequate to cure vitamin B12 deficiency, with a good safety profile. The efficacy was particularly marked when considering the noticeable improvement in serum vitamin B12 levels and haematological parameters, such as haemoglobin level, mean erythrocyte cell volume and reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. For nasal vitamin B12, only a few preliminary studies were available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 injections in elderly patients. Oral vitamin B12 treatment avoids the discomfort, inconvenience and cost of monthly injections.

The procurement of abdominal organs is a highly specialised operation, which marks the first important step for a successful transplantation. The article gives an overview of the organisation and the current state of the education of procurement surgeons in Germany. We comment on current challenges and discuss these in an international context.Die Entnahme abdomineller Organe zur Transplantation ist ein hochspezialisierter Eingriff, der den 1. Schritt zu einer erfolgreichen Transplantation darstellt. Im folgenden Artikel soll ein Überblick über die organisatorischen Rahmenbedingungen, die derzeitige Ausbildung der Entnahmechirurgen in Deutschland sowie die damit einhergehenden Herausforderungen gegeben und diese auch im internationalen Kontext diskutiert werden.

Private groundwater wells have the potential to be an unmonitored source of contaminants that can harm human health for millions of people throughout the United States. Developing models that predi...

Purpose To describe the occurrence of potential statin misuse, its characteristics and associated factors in older people. Methods A retrospective cross-sectional study was conducted in Alsace and Lorraine (France) using French health insurance databases. Study population comprised community-dwelling patients and nursing homes residents aged 80 and over, who received at least one statin prescription between January 1, 2017 to April 30, 2017 (N = 38 268). Potential statin misuse was identified considering off-label uses, high-intensity doses, drug contraindications and statin-drug interactions. Results At least one potential statin misuse was detected for 19 468 patients (50.9%). Off-label prescription was the most frequent misuse observed (53.6%), followed by high-intensity statin dose (30.5%). Polypharmacy (five to nine drugs) and excessive polypharmacy (10 or more drugs) were the main risk factors associated with potential statin misuse (adjusted OR = 2.6 and 4.7 respectively). Nursing home, multi-morbidity and the presence of multiple prescriptions from different doctors for the same patient were other risk factors significantly associated. Two sensitivity analyzes (reconsiderations of off-label and high statin dose definitions) revealed the same statistical trend. Conclusion Potential statin misuse is frequent in people aged 80 and over. These findings should serve as a warning to health care professionals and hopefully will contribute to ensure an appropriate and safe use of statin in aged population.

In dem Beitrag geht es um Kritik am heutigen kulturell und okonomisch gepragten Umgang mit den Dingen. Dabei wird eine kulturgeschichtliche und philosophische Entwicklungslinie unseres von Beschleunigung, Verschwendung und Uberfluss bestimmten Handelns nachgezeichnet. Der Beitrag verdeutlicht die Widersinnigkeit und Widerspruchlichkeit unserer gegenwartigen Produktions- und Konsumweise. Von der Umnutzung von Gebrauchsgutern fruherer Zeiten uber die Schnelllebigkeit im heutigen Umgang mit den Dingen (z. B. „Tempo-Taschentuch“) bis hin zur Absurditat industrieller Massenproduktion von gebraucht (historisch) erscheinenden Gutern („Used Look“) zeichnet der Beitrag eine Entwicklungslinie in Produktion und Konsumtion unserer Kulturgeschichte nach. Auf der Grundlage der Analyse werden philosophische Uberlegungen einer Kultur der Masigung und eines achtsameren, wertschatzenden Umgangs mit den Ressourcen und Dingen als Alternative zu den Imperativen einer Uberfluss- und Wegwerfgesellschaft aufgezeigt (vgl. Vogel, T. (2018). Masigung – Was wir von einer alten Tugend lernen konnen. Munchen: oekom.). Seit 2500 Jahren philosophieren Menschen uber Masigung als Ziel fur Zufriedenheit und Gluck. Der exzessive Produktions- und Lebensstil in den Industrielandern und die Zerstorung der naturlichen Lebensgrundlagen erfordern ein neues Nachdenken uber diese Philosophie als Suche nach dem rechten Mas im Verhaltnis des Menschen zu sich selbst, zur Natur und im Umgang mit den Dingen.

Thomas Vogel und Heike Frank-Ostarhild (Hrsg.): Neckargeschichten. Klöpfer & Meyer Tübingen 2010. Gebunden, 352 Seiten, € 22,–. ISBN 978-3-940086-46-4

The effectiveness of iron-based shape memory alloy (Fe-SMA, ‘memory-steel’) reinforcements has been proven in several studies and site applications. Due to the novelty of ribbed memory-steel reinforcement bars, limited research has been performed on their application in structural engineering, however. In this study, the bond behaviour of memory-steel bars in a near-surface-mounted configuration designed for prestressed strengthening of concrete structures was investigated. Memory-steel bars were installed on concrete blocks and activated by resistive heating before being subjected to pull-out load. The effects of heating and hence prestressing, bar ductility, bond length and rigidity of the fixation were studied based on obtained prestress, crack development, slip and bar strain. During activation of the bars, a longitudinal splitting crack with insignificant crack width occured. Two failure modes were observed during subsequent external loading, including tensile rupture of the bar when less ductile material was used, or bond failure when material with higher ductility was under investigation. Initial prestressing did not result in a reduced bond capacity. Based on the differential equation of bond behaviour, an analytical calculation procedure was developed that enables prediction of bond shear stress, slip, bar strain, pull-out load, as well as the use of a non-linear material behaviour., Materials & Design, 196, ISSN:0264-1275, ISSN:1873-4197

IntroductionEarly conversion to a CNI-free immunosuppression with SRL was associated with an improved 1- and 3- yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial.Methods and materialsN = 71 from 6 centers (n = 38 SRL and n = 33 CsA) of the original SMART-Trial (ITT n = 140) were enrolled in this observational, non-interventional extension study to collect retrospectively and prospectively follow-up data for the interval since baseline. Primary objective was the development of dnDSA. Blood samples were collected on average 8.7 years after transplantation.ResultsDevelopment of dnDSA was not different (SRL 5/38, 13.2% vs. CsA 9/33, 27.3%; P = 0.097). GFR remained improved under SRL with 64.37 ml/min/1.73m2 vs. 53.19 ml/min/1.73m2 (p = 0.044). Patient survival did not differ between groups at 10 years. There was a trend towards a reduced graft failure rate (11.6% SRL vs. 23.9% CsA, p = 0.064) and less tumors under SRL (2.6% SRL vs. 15.2% CsA, p = 0.09).ConclusionsAn early conversion to SRL did not result in an increased incidence of dnDSA nor increased long-term risk for the recipient. Transplant function remains improved with benefits for the graft survival.

To promote structurally flexible controllers in systems such as self-aware computing systems, this paper proposes the use of micro-controllers. Instead of generic monolithic controllers, like Rainbow, we advocate the use of service-specific micro-controllers which can be based on microservices. Although traditional generic controllers can be configured parametrically according to system needs, their use and reuse are nevertheless restrictive because of the wide range of services expected from the different stages of the feedback control loop. The solution being advocated is to have structurally flexible controllers that can be composed from micro-controllers. Controlling the architectural configuration of these micro-controllers is a meta-controller that is able to conFigure the controller according to the services required for controlling the target system. The feasibility of the proposed approach is demonstrated using the PhoneAdapter case study in which micro-controllers are configured at run-time depending on changes affecting the system or its environment.

Modern surgical methods are becoming increasingly sophisticated and the number of technical devices that are used during these interventions is increasing. However, the surgical operating room (OR) remains a mere conglomerate of unconnected medical devices. The increase in the complexity of device functionality, in addition to the demands of surgery, pushes human mental capacity to its limit. Hence, an "intelligent" collaborative support system would be more than welcome. We envision a "human-like" intelligent system, which could support the surgical team as a situation-aware consultant. This so-called "active collaborative support system" (ACSS) is based on four main pillars: real-time data inflow, a comprehensive knowledge-base, access to the Internet of Things (surgical devices), and an understanding of human language through natural language processing. Recent advances in the area of AI are bringing this ambitious goal within reach, but there is still a considerable amount of work to be done, including the establishment of a new way of thinking in the collaboration between surgeons and computer scientists/engineers, and possibly one day with intelligent machines-provided that AI systems can be sufficiently trusted.

Self-adaptation can be realized in various ways. Rule-based approaches prescribe the adaptation to be executed if the system or environment satisfies certain conditions. They result in scalable solutions but often with merely satisfying adaptation decisions. In contrast, utility-driven approaches determine optimal decisions by using an often costly optimization, which typically does not scale for large problems. We propose a rule-based and utility-driven adaptation scheme that achieves the benefits of both directions such that the adaptation decisions are optimal, whereas the computation scales by avoiding an expensive optimization. We use this adaptation scheme for architecture-based self-healing of large software systems. For this purpose, we define the utility for large dynamic architectures of such systems based on patterns that define issues the self-healing must address. Moreover, we use pattern-based adaptation rules to resolve these issues. Using a pattern-based scheme to define the utility and adaptation rules allows us to compute the impact of each rule application on the overall utility and to realize an incremental and efficient utility-driven self-healing. In addition to formally analyzing the computational effort and optimality of the proposed scheme, we thoroughly demonstrate its scalability and optimality in terms of reward in comparative experiments with a static rule-based approach as a baseline and a utility-driven approach using a constraint solver. These experiments are based on different failure profiles derived from real-world failure logs. We also investigate the impact of different failure profile characteristics on the scalability and reward to evaluate the robustness of the different approaches., arXiv admin note: text overlap with arXiv:1805.03549

Background: COVID-19 is a disease of the elderly as 95% of deaths related to COVID-19 occur in people over 60 years of age. Despite the urgent need for a preventive treatment there are currently no serious leads, other than the vaccination. Objective: To find a preventive treatment of COVID-19 in elderly patients. Design: Retrospective case-control study. Setting: Robertsau Geriatric Hospital of the University Hospitals of Strasbourg, France. Patients: 179 elderly patients who had been in contact with the SARS-CoV-2, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Measurements: Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), paracetamol, anticoagulant, oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected using the electronic patient record. Results: COVID-pos patients more frequently had a history of diabetes (P=.016) and alcoholism (P=.023), a lower leukocyte count (P=.014) and a higher mortality rate– 29.2% versus 14.4% – (P=.014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P=.0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-19 patients on antipsychotics (P=.0013) and OADs (P=.0166) were less likely to die. Limitations: retrospective study. Conclusion: PPIs treatment lowered the risk of development of COVID-19 infection, and antipsychotics and OADs decreased the risk of mortality in geriatric patients. If further studies confirm this finding, PPIs could be used preventatively in the elderly in this pandemic context. Moreover, OADS and antipsychotics should be tested in clinical trials.

COVID-19 is a particularly aggressive disease for the elderly as 86% of deaths related to COVID-19 occur in people over 65 years of age. Despite the urgent need for a preventive treatment, there are currently no serious leads, other than the vaccination. The aim of this retrospective case-control study is to find a pharmacological preventive treatment of COVID-19 in elderly patients. One-hundred-seventy-nine patients had been in contact with other COVID-19 patients at home or in hospital, of whom 89 had tested RT-PCR-positive (COVID-pos) for the virus and 90 had tested RT-PCR-negative (COVID-neg). Treatments within 15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected. COVID-pos patients more frequently had a history of diabetes (P = .016) and alcoholism (P = .023), a lower leukocyte count (P = .014) and a higher mortality rate — 29.2% versus 14.4% — (P = .014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P = .0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-pos patients on antipsychotics (P = .0013) and OADs (P = .0153), particularly metformin (P = .0237), were less likely to die. Thus, patients on treatment with PPI were less likely to develop COVID-19 infection, and those on antipsychotics or metformin had a lower risk of mortality. However, prospective studies, including clinical trials, are needed to confirm or not these findings. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-021-00397-z.

Aim: The present study aims to evaluate protective effects of a novel histidine–tryptophan–ketoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. Methods: Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4°C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs–Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. Results: The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia–reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. Conclusion: HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.

The aim of the study was to explore whether abstinent patients on recent opioid detoxification or on opioid maintenance treatment suffer from sleeping problems. 199 patients on opioid maintenance treatment (methadone, diacetylmorphine and buprenorphine) or recent opioid detoxification were included in this exploratory cross-sectional study. We used the Pittsburgh Sleep Quality Index (PSQI) and the Regensburger Insomnia Scale (RIS) in order to assess potential sleeping problems. There was a significant effect of the condition "opioid maintenance" or "recent opioid detoxification" on the total score of PSQI and RIS. All opioid maintenance drugs used by the study population were associated with more sleeping problems compared to the detoxification group when calculated with RIS values. Recently abstinent patients (opioid detoxification) displayed significantly fewer sleep disturbances than opioid-maintained patients. Since sleeping problems can seriously impair treatment success and quality of life, screening for sleep disturbances and their subsequent treatment is of pronounced relevance.

With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combined geographical and epidemiological data with whole genome sequencing of influenza viruses at the scale of urban quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed annually re-occurring geographic clusters of influenza incidences, mainly associated with net income, and independent of population density and living space. Vaccination against influenza was also mainly associated with household income and was linked to the likelihood of influenza-like illness within an urban quarter. Transmissions patterns within and between quarters were complex. High-resolution city-level epidemiological studies combined with social science surveys such as this will be essential for understanding seasonal and pandemic transmission chains and delivering tailored public health information and vaccination programs at the municipal level.

Introduction: Falls among older people are a major health issue and the first cause of accidental death after 75 years of age. Post-fall syndrome (PFS) is commonly known and yet poorly studied. Objective: Identify risk factors for PFS and do a follow-up 1 year later. Methods: We included all patients over 70 years of age hospitalized after suffering a fall in a case-control study, and then followed them in a cohort study. PFS was retained in case of functional mobility decline (transferring, walking) occurring following a fall in the absence of an acute neurological, orthopedic or rheumatic pathology directly responsible for the decline. The data initially collected were: clinical (anamnestic, emergency and departmental/ward evolution, medical history, lifestyle, treatments, clinical examination items); and imaging if the patient had been subjected to brain imaging in the last 3 years prior to inclusion. Regarding the follow-up at 1 year, we collected from the general physician the occurrence and the characteristics of new falls, functional mobility assessment, hospitalization and death. Results: Inclusion took place from March 29, 2016 to June 7, 2016 and follow-up until June 30, 2017. We included 70 patients. A total of 29 patients exhibited a PFS (41.4 %). Risk factors for PFS included age, walking disorder prior to the fall, the use of a walking aid prior to the fall, no unaccompanied outdoor walk in the week before the fall, visual impairment making close reading impossible, stiffness in ankle dorsiflexion, grip strength and the fear of falling. Among patients with PFS, 52.9% could still perform a transfer at 1 year and 64.7% could still walk against 80.7% and 85.2%, respectively, for patients without PFS. Conclusion: The study showed the existence of body functions/structure impairments and activity limitations prior to the fall among patients exhibiting a PFS. This suggests the existence of a pre-fall syndrome, i.e., a psychomotor disadaptation syndrome existing prior to the fall. Among the 8 risk factors, fear of falling, vision impairment and muscle strength could be targeted for improvement. The diagnosis of PFS could be a marker of loss of functional mobility at 1 year.

Context: In search-based software engineering we often use popular heuristics with default configurations, which typically lead to suboptimal results, or we perform experiments to identify configurations on a trial-and-error basis, which may lead to better results for a specific problem. We consider the problem of generating test suites for mobile applications (apps) and rely on \Sapienz, a state-of-the-art approach to this problem that uses a popular heuristic (NSGA-II) with a default configuration. Objective: We want to achieve better results in generating test suites with \Sapienz while avoiding trial-and-error experiments to identify a more suitable configuration of \Sapienz. Method: We conducted a fitness landscape analysis of \Sapienz to analytically understand the search problem, which allowed us to make informed decisions about the heuristic and configuration of \Sapienz when developing \SapienzDiv. We comprehensively evaluated \SapienzDiv in a head-to-head comparison with \Sapienz on 34 apps. Results: Analyzing the fitness landscape of \Sapienz, we observed a lack of diversity of the evolved test suites and a stagnation of the search after 25 generations. \SapienzDiv realizes mechanisms that preserve the diversity of the test suites being evolved. The evaluation showed that \SapienzDiv achieves better or at least similar test results than \Sapienz concerning coverage and the number of revealed faults. However, \SapienzDiv typically produces longer test sequences and requires more execution time than \Sapienz. Conclusions: The understanding of the search problem obtained by the fitness landscape analysis helped us to find a more suitable configuration of \Sapienz without trial-and-error experiments. By promoting diversity of test suites during the search, improved or at least similar test results in terms of faults and coverage can be achieved., Comment: Accepted Manuscript. arXiv admin note: text overlap with arXiv:1906.08142

This research bridges the gap between the numerical layout optimization method and the geometry-based analysis and design method of graphic statics. The study connects the two methods for the application of strut-and-tie models in reinforced concrete design. It suggests a new algorithm for the algebraic graphic statics of indeterminate trusses inspired by the layout optimization method. This research also contributes to the field of graphic statics by providing a formulation that generates form and force diagrams in a continuum, where the topology for none of the diagrams is initially provided. The generation of strut-and-tie models for reinforced concrete has extensively relied on optimization methods, which are helpful techniques for the initiation of a load path inside a continuous domain. However, the resulting truss model is a single answer, and there exists limited control to methodically modify the topology or the force distribution of the model. Furthermore, the minimized-weight truss does not guarantee a practical strut-and-tie model or an optimized performance of a reinforcement design. In contrast to the conventional optimization techniques with a single solution, the intuitive method of graphic statics provides the designer with a vast design space. It also offers explicit control over the geometry and force distribution of the generated truss models. The algorithm provided in this paper is applied to various continuous domains to systematically generate a variety of strut-and-tie models, their force diagrams, and constant stress fields. The production of the optimized truss model and its force distribution allows the direct interactive manipulations of the design while observing the changes in the stress fields and the reinforcement arrangement. The open-source repository of the implemented integrated algorithm and the examples used in this paper are also provided., Computers & Structures, 240, ISSN:0045-7949

Anyone working in the technology sector is probably familiar with the question: “Have you tried turning it off and on again?”, as this is usually the default question asked by tech support. Similarly, it is known in search-based testing that metaheuristics might get trapped in a plateau during a search. As a human, one can look at the gradient of the fitness curve and decide to restart the search, so as to hopefully improve the results of the optimization with the next run. Trying to automate such a restart, it has to be programmatically decided whether the metaheuristic has encountered a plateau yet, which is an inherently difficult problem. To mitigate this problem in the context of theoretical search problems, the Bet and Run strategy was developed, where multiple algorithm instances are started concurrently, and after some time all but the single most promising instance in terms of fitness values are killed. In this paper, we adopt and evaluate the Bet and Run strategy for the problem of test case generation. Our work indicates that use of this restart strategy does not generally lead to gains in the quality metrics, when instantiated with the best parameters found in the literature.

Contract-based design (CBD) is an emerging paradigm for complex systems, specifying the input-output behavior of a component by defining what the component guarantees, provided its environment satisfies the given assumptions. Under certain circumstances, it is possible to verify the decomposition of contracts to conclude the correctness of the top-level system requirements. Verification is performed by using model checkers. If the decomposition of the contract is found to be incorrect, a model checker generates a counterexample. However, the challenging task is to understand the counterexample, which usually is lengthy, cryptic, and verbose. In this paper, we propose an approach to derive an understandable error explanation for counterexamples in CBD. In addition, we highlight the erroneous variables and erroneous states in the counterexample, which reduces the effort to identify errors. Therefore, our approach supports error comprehension of the original counterexample. Our approach is evaluated based on two industrial use cases, the Bosch Electronic Power Steering (EPS) and a redundant sensor system.

Um die Zusammenarbeit der beteiligten Institutionen im Rahmen der Jugendberufsagenturen zu verbessern, Transparenz uber die verschiedenen Unterstutzmoglichkeiten der einzelnen Rechtskreise zu schaffen und Angebote zielgerichtet aufeinander abzustimmen wurde die „virtuelle JugendBerufsAgentur“ entwickelt. Im Beitrag wird die Entstehungs- und Entwicklungsgeschichte des Vorhabens skizziert. Es werden die datenschutzrechtlichen Anforderungen und die funktionelle Umsetzung beschrieben. Abschliesend gehen die Autoren auf die aktuellen Entwicklungen ein und geben einen Ausblick.

Control theoretical techniques have been successfully adopted as methods for self-adaptive systems design to provide formal guarantees about the effectiveness and robustness of adaptation mechanisms. However, the computational effort to obtain guarantees poses severe constraints when it comes to dynamic adaptation. In order to solve these limitations, in this paper, we propose a hybrid approach combining software engineering, control theory, and AI to design for software self-adaptation. Our solution proposes a hierarchical and dynamic system manager with performance tuning. Due to the gap between high-level requirements specification and the internal knob behavior of the managed system, a hierarchically composed components architecture seek the separation of concerns towards a dynamic solution. Therefore, a two-layered adaptive manager was designed to satisfy the software requirements with parameters optimization through regression analysis and evolutionary meta-heuristic. The optimization relies on the collection and processing of performance, effectiveness, and robustness metrics w.r.t control theoretical metrics at the offline and online stages. We evaluate our work with a prototype of the Body Sensor Network (BSN) in the healthcare domain, which is largely used as a demonstrator by the community. The BSN was implemented under the Robot Operating System (ROS) architecture, and concerns about the system dependability are taken as adaptation goals. Our results reinforce the necessity of performing well on such a safety-critical domain and contribute with substantial evidence on how hybrid approaches that combine control and AI-based techniques for engineering self-adaptive systems can provide effective adaptation.

Two of the main paradigms used to build adaptive software employ different types of properties to capture relevant aspects of the system's run-time behavior. On the one hand, control systems consider properties that concern static aspects like stability, as well as dynamic properties that capture the transient evolution of variables such as settling time. On the other hand, self-adaptive systems consider mostly non-functional properties that capture concerns such as performance, reliability, and cost. In general, it is not easy to reconcile these two types of properties or identify under which conditions they constitute a good fit to provide run-time guarantees. There is a need of identifying the key properties in the areas of control and self-adaptation, as well as of characterizing and mapping them to better understand how they relate and possibly complement each other. In this paper, we take a first step to tackle this problem by: (1) identifying a set of key properties in control theory, (2) illustrating the formalization of some of these properties employing temporal logic languages commonly used to engineer self-adaptive software systems, and (3) illustrating how to map key properties that characterize self-adaptive software systems into control properties, leveraging their formalization in temporal logics. We illustrate the different steps of the mapping on an exemplar case in the cloud computing domain and conclude with identifying open challenges in the area.

A fuzzer provides randomly generated inputs to a targeted software to expose erroneous behavior. To efficiently detect defects, generated inputs should conform to the structure of the input format and thus, grammars can be used to generate syntactically correct inputs. In this context, fuzzing can be guided by probabilities attached to competing rules in the grammar, leading to the idea of probabilistic grammar-based fuzzing. However, the optimal assignment of probabilities to individual grammar rules to effectively expose erroneous behavior for individual systems under test is an open research question. In this paper, we present EvoGFuzz, an evolutionary grammar-based fuzzing approach to optimize the probabilities to generate test inputs that may be more likely to trigger exceptional behavior. The evaluation shows the effectiveness of EvoGFuzz in detecting defects compared to probabilistic grammar-based fuzzing (baseline). Applied to ten real-world applications with common input formats (JSON, JavaScript, or CSS3), the evaluation shows that EvoGFuzz achieved a significantly larger median line coverage for all subjects by up to 48% compared to the baseline. Moreover, EvoGFuzz managed to expose 11 unique defects, from which five have not been detected by the baseline.

Les antiagregants plaquettaires sont des medicaments dont le benefice dans les maladies cardiovasculaires est prouve. Leur utilisation concerne 5,6 % de la population francaise. En prevention secondaire, des recommandations etablies a partir d’essais cliniques encadrent la prescription des antiagregants plaquettaires dans la population generale. En prevention primaire, leur utilisation est controversee, car ils sont associes a une augmentation du risque hemorragique, en particulier digestif et cerebral. Du fait de l’heterogeneite de la population geriatrique et en l’absence d’etudes ciblees, l’application stricte des indications admises pour la population generale est complexe. Dans cet article, il est propose de faire le point sur les recommandations concernant l’utilisation des antiagregants plaquettaires en fonction des principales situations cliniques dans la population generale et d’emettre des suggestions concernant la prise en charge des patients de plus de 75 ans.

Background A reliable and sterile access through the intestinal wall to ease flexible endoscopic transluminal interventions is still appealing but lacks a suitable port system. Methods In a granted industry cooperation, we developed the MIEO-Port, a flexible three components overtube system that provides a temporary hermetic sealing of the intestinal wall to allow endoscopic disinfection and manipulation to gain access to the abdominal cavity. The port features an innovative head part which allows for coupling the port to the intestinal wall by vacuum suction and for controlled jetting the isolated intestinal surface with a disinfectant. The device was tested in vivo in 6 pigs for acute and long-term usability. All animal tests were approved by the local ethics committee. Results In the acute experiment, the port system supported sealed endoscopic mucosa resection and transluminal cholecystectomy. In the survival study on 5 animals, the MIEO-Port proved its reliability after transcolonic peritoneoscopy. In one animal, a port dislocation occurred after extensive retroperitoneal preparation, one animal revealed bacterial contamination at necropsy; however, all animals showed a favourable course over ten days and offered no signs of peritonitis or abscedation during post-mortem examination. Discussion To the best of our knowledge, the MIEO-Port system is the first device to provide a reliable and sterile flexible access to the peritoneal cavity that can be used throughout the entire gastrointestinal tract regardless of the access route and which combines hermetic sealing with local sterilization. Further studies are warranted.

Background Ageing is intrinsically associated with a progressive decline in cardiorespiratory fitness (CRF) as measured by peak oxygen uptake (VO2peak ). Improving CRF through physical activity contribute to better and healthy ageing. High-intensity interval training (HIIT) is a potent method of improving CRF among seniors, yet comparisons between this type of training and traditional endurance training (ET) are equivocal especially among older adults. Purpose To analyse the effects of HIIT and ET on the VO2peak of seniors aged 65 years or older when compared with controls and also when the two types of training were compared with one another. Methods A comprehensive, systematic database search for manuscripts was performed in Embase, Medline, PubMed Central, ScienceDirect, Scopus and Web of Science using key words. Two reviewers independently assessed interventional studies for potential inclusion. Fifteen randomized controlled trials (RCTs) were included totalling 480 seniors aged 65 years or over. Across the trials, no high risk of bias was measured. Results In pooled analysis of the RCTs, the VO2peak was significantly higher after ET sessions compared with controls (mean difference-MD = 1.35; 95% confidence interval-CI: 0.73-1.96). Furthermore, VO2peak was found significantly higher not only when compared HIIT with controls (MD = 4.61; 95% CI: 3.21-6.01), but also when compared HIIT with ET (MD = 3.76; 95% CI: 2.96-4.56). Conclusion High-intensity interval training and ET both elicit large improvements in the VO2peak of older adults aged 65 or over. When compared with ET, the gain in VO2peak was greater following HIIT. Nevertheless, further RCTs are therefore needed to confirm our results in senior's population.

International audience; Interval aerobic training programs (IATP) improve cardiorespiratory and endurance parameters. They are, however, unsuitable to seniors as frequently associated with occurrence of exhaustion and muscle pain. The purpose of this study was to measure the benefits of an IATP designed with recovery bouts (IATP-R) in terms of cardiorespiratory and endurance parameters and its acceptability among seniors (≥70 years). Sedentary healthy volunteers were randomly assigned either to IATP-R or sedentary lifestyle. All participants performed an incremental cycle exercise and 6-minute walk test (6-MWT) at baseline and 9.5 weeks later. The first ventilatory threshold (VT1 ); maximal tolerated power (MTP); peak of oxygen uptake (VO2peak ); maximal heart rate (HRmax ); and distance walked at 6-MWT were thus measured. IATP-R consisted of 19 sessions of 30-minute (6 × 4-min at VT1 + 1-minute at 40% of VT1 ) cycling exercise over 9.5 weeks. With an adherence rate of 94.7% without any significant adverse events, 9.5 weeks of IATP-R, compared to controls, enhanced endurance (VT1 : +18.3 vs -4.6%; HR at baseline VT1 : -5.9 vs +0.2%) and cardiorespiratory parameters (VO2peak : +14.1 vs -2.7%; HRmax : +1.6 vs -1.7%; MTP: +19.2 vs -2.3%). The walk distance at the 6-MWT was also significantly lengthened (+11.6 vs. -3.1%). While these findings resulted from an interim analysis planned when 30 volunteers were enrolled in both groups, IATP-R appeared as effective, safe, and applicable among sedentary healthy seniors. These characteristics are decisive for exercise training prescription and adherence.

Little is known concerning the interaction of achalasia and pregnancy and about an optimal time and type for treatment. Achalatic women of our collective of patients with at least one pregnancy in their history resulting in confinement or miscarriage were invited for a structured interview. 43 of 109 female patients were included. Questionnaire contained questions on symptoms, type of symptoms, whether patients could link a specific event with outbreak of disease. Date of primary diagnosis and individual therapies were double checked against our documentation as well as duration of complaints and kind of therapy. Patients were asked about their obstetric history, whether and how symptoms had changed, and during which pregnancy week symptoms have occurred. Temporal correlation of the diagnosis of achalasia and pregnancy was investigated. There was no relationship between pregnancy and onset of achalasia. Risk of subfertility, undernourishment, premature birth, or miscarriage does not seem to be increased in achalasia. Health condition often worsened significantly during pregnancy, mainly in the first trimester and particularly in the untreated patients. It is advisable to clarify the diagnosis if symptoms suspicious of an achalasia are present before a planned pregnancy. In case of manifest achalasia, surgical treatment should be performed before pregnancy and the improvement in the state of health should be anticipated, as, otherwise, a considerable deterioration of the symptoms during pregnancy may occur. Scientific impact of our observations is very limited and prospective clinical trials are required.

This paper describes a computer simulation and measurements of the liquid phase of Diesel spray formation. The spray is divided into small elementary volumes in which the amounts of liquid and gaseous fuel, air, mean, maximum and minimum fuel droplet diameter are calculated, as well as their number. The total air–fuel and air–fuel vapour ratios are calculated for each elementary volume. The mathematical model of the Diesel spray is based on continuity and momentum equations in Eulerian-Lagrangian formulation. The measurements of the sprays were carried out in the combustion chamber at the LTT, which is equipped with a high pressure 250 MPa fuel injection system. During the experiments, ambient pressure varied from 3 MPa to 7 MPa, temperature from 673 K to 973 K, injection pressure from 40 MPa to 200 MPa and nozzle temperature from 243 K to 363 K. The injection quantity was 13.5 mm3 per cycle in all cases. The combustion chamber was filled with pure nitrogen instead of air. Thermodynamic properties of nitrogen are similar to those of air. That way, self-ignition was prevented. We measured only the liquid phase of the fuel in the spray, and to this end, Mie scattering measuring technique was applied. The comparison between the simulated and actual liquid spray penetration depth and spray cone angle showed good matching.