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The primary means for electronic position fixing in use in contemporary maritime transport are shipborne GPS (Global Positioning System) receivers or DGPS (Differential GPS) receivers. More advanced GNSS (Global Navigation Satellite System) or RNSS (Regional Navigation Satellite Systems) receivers are able to process combined signals from American GPS, Russian GLONASS, Chinese Beidou (BDS), European Galileo, Indian IRNSS, and Japan QZSS. Satellite-based augmentation systems (SBAS) are still not commonly used in the maritime domain, especially onboard vessels certified under international SOLAS convention. The issues and weaknesses of existing International Maritime Organization recommendations, guidelines, requirements, performance standards, and policies on GNSS shipborne sensors are discussed and presented in the paper. Many problems that have already been dealt with in other means of transportation are still to be solved in the maritime domain. The integrity monitoring is addressed as the main issue, and recommendations based on solutions implemented in aviation and the latest research are proposed. Finally, the strengths, weaknesses, opportunities, and threats awaiting maritime GNSS standardization process are outlined.

Purpose: We analyzed the effects of COVID-19 as well as its accompanying epidemiological control measures on health-related outcomes (physical and mental health) and unmet care needs of both caregivers and care recipients across Europe and Israel by taking into account country differences.Methods: We applied comparisons of adjusted predictions, controlling for a large set of relevant respondent characteristics, to investigate changes in the physical and mental health of caregivers and care recipients due to COVID-19. Furthermore, multilevel regression models were used to analyze the effect of individual and contextual indicators on the probability of reporting difficulties in receiving care. For the analyses, we used data from 26 countries with 51,983 respondents over 50 years based on the eighth wave of the Survey of Health, Aging and Retirement in Europe (SHARE), which had to be suspended in March 2020, and the SHARE Corona Survey fielded from June to August 2020.Results: During the first phase of the pandemic in spring/summer 2020, the frequency of providing personal care to parents increased in almost all European countries, while care to children, in turn, decreased. Parental caregivers who increased the frequency of providing personal care reported significantly more mental health strains, that is, feeling sad/depressed and anxious/nervous more often since the outbreak of the pandemic. With respect to receiving care, about one out of five care recipients had difficulty in obtaining adequate care from outside the household during the pandemic. The perception of unmet care needs was significantly associated with country differences regarding the duration of the stay-at-home orders. In contrast, the number of confirmed deaths did not have a significant effect on perceiving difficulties related to receiving care.Conclusions: Our findings show the extent of the burden to which caregivers and care recipients were exposed with respect to the unintended consequences of COVID-19-related epidemiological control measures. There is a great need within this population for interventions, which effectively reduce the burden as well as the symptoms of anxiety or depression for caregivers as well as care recipients. This should be recognized by (health) policymakers and social organizations.

BackgroundRobotic surgery holds particular promise for complex oncologic colorectal resections, as it can overcome many limitations of the laparoscopic approach. However, similar to the situation in laparoscopic surgery, appropriate case selection (simple vs. complex) with respect to the actual robotic expertise of the team may be a critical determinant of outcome. The present study aimed to analyze the clinical outcome after robotic colorectal surgery over time based on the complexity of the surgical procedure.MethodsAll robotic colorectal resections (n = 85) performed at the Department of Surgery, Medical University of Vienna, between the beginning of the program in April 2015 until December 2019 were retrospectively analyzed. To compare surgical outcome over time, the cohort was divided into 2 time periods based on case sequence (period 1: patients 1–43, period 2: patients 44–85). Cases were assigned a complexity level (I-IV) according to the type of resection, severity of disease, sex and body mass index (BMI). Postoperative complications were classified using the Clavien-Dindo classification.ResultsIn total, 47 rectal resections (55.3%), 22 partial colectomies (25.8%), 14 abdomino-perineal resections (16.5%) and 2 proctocolectomies (2.4%) were performed. Of these, 69.4% (n = 59) were oncologic cases. The overall rate of major complications (Clavien Dindo III-V) was 16.5%. Complex cases (complexity levels III and IV) were more often followed by major complications than cases with a low to medium complexity level (I and II; 25.0 vs. 5.4%, p = 0.016). Furthermore, the rate of major complications decreased over time from 25.6% (period 1) to 7.1% (period 2, p = 0.038). Of note, the drop in major complications was associated with a learning effect, which was particularly pronounced in complex cases as well as a reduction of case complexity from 67.5% to 45.2% in the second period (p = 0.039).ConclusionsThe risk of major complications after robotic colorectal surgery increases significantly with escalating case complexity (levels III and IV), particularly during the initial phase of a new colorectal robotic surgery program. Before robotic proficiency has been achieved, it is therefore advisable to limit robotic colorectal resection to cases with complexity levels I and II in order to keep major complication rates at a minimum.

Preservation of cognitive function is one of the major concerns in contemporary ageing societies. At the same time, overweight and obesity, which have been identified as risk factors for poor health development, have been increasing in many countries all over the world. This study examines the relationship between bodyweight change and cognitive decline in old age and it aims to determine whether and how changes in body mass index (BMI) affect the development of cognitive functioning in old age. Using longitudinal data from the Survey of Health, Ageing and Retirement in Europe (SHARE), covering four waves between 2006 and 2016 with 58,389 participants from 15 countries aged 50+, we estimated asymmetric fixed effects models by gender, adding possible confounding variables such as age, grip strength, health conditions, and physical activity. Additionally, we investigated possible heterogeneity in the BMI-cognition relation. We found a positive association between BMI change and change in cognitive performance, which was dominantly driven by BMI decrease. Weight loss was typically negatively related to cognition, particularly at low levels of BMI and mainly due to health conditions affecting both bodyweight and cognitive performance. Weight gain was, on average, not significantly related to cognitive performance; only respondents with preceding weight loss profited from small increases in BMI. Our analyses provide no support for an "obesity paradox" in cognition, according to which higher weight preserves cognition in old age. The association between weight change and cognitive performance in older age is based on weight changes being related to illness and recovery.

Physical activity (PA) in school physical education (PE) is a signature component of health promotion and health education. The study's aim was to explore PA levels and sedentary time in German elementary school PE lessons and relate them to selected personal and environmental PA determinants. Accelerometer measurements were collected from 328 students (47% male, mean age 8.7 ± 1.2 years) in 11 elementary schools in Baden-Wuerttemberg (Germany). PA levels and sedentary time were analyzed regarding gender, grade, body mass index, selected correlates of active living and health behaviors, as well as the PE teachers' PE education status. In line with previous research, the analyses of PA levels and sedentary time confirm gender and grade differences and highlight older girls as the less active group. Deviant weight status and parents' PA levels were found to be important determinants for PA levels and sedentary time of girls and offer starting points for intervention studies as well as gender-appropriate PE in elementary schools. Specialist PE teacher status proved to be a negative determinant of PA levels and sedentary time for boys and girls and should be investigated in further studies, especially regarding the didactic and methodological background.

While the COVID-19 crisis resulted in a vast number of new research projects springing up like mushrooms everywhere, it had severe consequences for ongoing survey research and in particular for running data collections. The Survey of Health, Ageing and Retirement in Europe (SHARE) was hit by the virus in the middle of its Wave 8 data collection, which had to be suspended in all 28 participating countries. Responding to the evolving crisis situation and taking steps to resume fieldwork was especially challenging for SHARE, since (1) the 50+ population is more severely affected by COVID-19 than younger age groups and (2) the measures taken by governments in response to the outbreak differed across the countries. Against this background, we discuss possible solutions for adaptations regarding the mode of data collection, questionnaire content, sample design, and actual fieldwork.

Immunotherapy has moved to the forefront of cancer treatment, illustrated by the accelerating pace of novel therapy approvals. In this complex environment, scientists rely on cutting edge conferences to stay informed. The Immunotherapy of Cancer (ITOC) conference was established jointly with the Society of the Immunotherapy of Cancer to bring the European researchers together. In its sixth edition, the ITOC conference has recently been held in Vienna, Austria.

Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses) grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses). Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy. Keywords: influenza A virus, neutrophilic elastase, oncolytic virotherapy, tumor immunology

The ultrastructural findings of the bone marrow cells from 15 patients with acquired sideroblastic anemia are presented. The red cell precursors from all patients showed the presence of electron-dense material in the mitochondria, representing most probably iron deposits. A great number of these mitochondria were completely destroyed. The erythropoietic precursors from one of the patients showed markedly elongated mitochondria that measured up to 3 μm. In addition numerous cytoplasmic vacuoles were observed. The red cell precursors from 60% of the patients showed signs of dyserythropoiesis, such as incomplete nuclear division and nuclear distortion. The polymorphonuclears from 47% of the patients presented nuclear abnormalities expressed as nuclear bridges, appendices, and blebs. In addition, phagocytosis of red blood cells was observed. The results of the study underline the advantages of the transmission electron microscope examination in visualization of intricate alterations in hematopoietic cells that cannot be detected with a light microscope. Microsc. Res. Tech. 63:155–158, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

T cells in colorectal cancer (CRC) are associated with improved survival. However, checkpoint immunotherapies antagonizing the suppression of these cells are ineffective in the great majority of patients. To better understand the immune cell regulation in CRC, we compared tumor-associated T lymphocytes and macrophages to the immune cell infiltrate of normal mucosa. Human colorectal tumor specimen and tumor-distant normal mucosa tissues of the same patients were collected. Phenotypes and functionality of tissue-derived T cells and macrophages were characterized using immunohistochemistry, RNA in situ hybridization, and multiparameter flow cytometry. CRC contained significantly higher numbers of potentially immunosuppressive CD39 and Helios-expressing regulatory T cells in comparison to normal mucosa. Surprisingly, we found a concomitant increase of pro-inflammatory IFNγ -producing T cells. PD-L1+ stromal cells were decreased in the tumor tissue. Macrophages in the tumor compared to tumor-distant normal tissue appear to have an altered phenotype, identified by HLA-DR, CD14, CX3CR1, and CD64, and tolerogenic CD206+ macrophages are quantitatively reduced. The prognostic effect of these observed differences between distant mucosa and tumor tissue on the overall survival was examined using gene expression data of 298 CRC patients. The combined gene expression of increased FOXP3, IFNγ, CD14, and decreased CD206 correlated with a poor prognosis in CRC patients. These data reveal that the CRC microenvironment promotes the coexistence of seemingly antagonistic suppressive and pro-inflammatory immune responses and might provide an explanation why a blockade of the PD1/PD-L1 axis is ineffective in CRC. This should be taken into account when designing novel treatment strategies.

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

PURPOSE:Little is known about the perioperative dynamic of albumin and its effect on surgical outcome in Crohn's disease. Thus, we aimed to assess postoperative changes of albumin levels and their potentially predictive role for complications after laparoscopic intestinal resections. METHODS:We identified 182 patients who underwent laparoscopic intestinal resection for symptomatic Crohn´s disease between 2000 and 2014 for this retrospective cohort study. Pre- and postoperative serum albumin levels (within 4 days) were recorded retrospectively and proportional postoperative reduction (delta (Δ) albumin) was calculated. Complications were defined according to the Clavien-Dindo classification. Univariate and multivariate analysis describing an eventful postoperative course were conducted. RESULTS:Complications were found in 22.5% (n = 41), 6% (n = 11) developed major complications defined as Clavien Dindo III-V and 16.5% (n = 30) had minor complications (Clavien Dindo I-II). The median Δ albumin was 22.75% (range: -18.46-47.14%). Delta albumin was found to be significantly higher in patients who developed complications after surgery (p = 0.03). Notably, neither preoperative (p = 0.28) nor postoperative albumin levels (p = 0.41) taken as absolute numerical values correlated with an eventful course following intestinal resection. In the multivariate analysis, based on a cut-off of 24.27%, Δ albumin remained an independent factor for surgical complications (p = 0.04, OR 2.232) next to conversion rate (p

The role of visceral fat measured by computer tomography is yet not well defined in patients with Crohn's disease. Therefore, the present study was designed to assess the impact of visceral fat area on postoperative short-term outcome and surgical characteristics. We analyzed 95 patients, who underwent intestinal resection for symptomatic Crohn's disease at an academic tertiary referral center between 2003 and 2008. Visceral fat area was measured on preoperative computed tomography scans. Postoperative morbidity was graded according to the Clavien-Dindo classification. Visceral fat area was correlated with baseline characteristics, disease phenotype and 30-day morbidity. Body mass index and age were significantly associated with a higher visceral fat area (p = 0.001). Overall 19 (20.0%) postoperative complications were observed, of whom 7 (7.4%) patients required surgical re-intervention. No significant difference was found with regard to visceral fat area between patients with an uneventful and eventful postoperative course (no complications: median visceral fat area 52.0 cm2 SD 59.7, complications: 41.3 cm2 SD 42.8; p = 0.465). In contrast to current literature, we cannot support the role of visceral fat area for predicting postoperative course in Crohn's disease. In addition, no correlation of the visceral fat area and disease behavior was detected.

The current systems supporting navigation on board of ships are built on the classic concept for equipment: The system is developed, tested, type approved, installed and from that time on used with no or little modifications. Looking at other industries a regime of software and system maintenance has been established which allows more rapid updates. The development in the IT arena moves more towards modular approached, encapsulating individual components for easier implementation and delivery with limited system wide impact. This key concept is lately often referred to as the “app concept”. The e-Navigation development asks for exactly that: a way to improve innovation while ensuring system stability for the navigational components used by the navigator on the bridge. A key aspect of the success of new systems will be the ability to convert data into as information as needed in any given situation, creating knowledge for intelligent decisions increasing the competence of a navigator. The paper will focus on the following topics: – The classic “monolithic” Equipment paradigm – Modern System Architecture using components and “apps”-concept – Advantages of an approach using situational driven tool enhancements – The “app”-concept supporting the situational centric information presentation

e-Navigation, a theme introduced but IMO to improve safety of navigation at sea, is starting to gain traction in various organizations. As the concept develops, the importance of data, both static as well as dynamic, is more and more realized. IALA and IHO, in their efforts to help making e-Navigation a reality, have agreed to propose the IHO GI Register (often known as S-100 Register) as the conceptual basis for the Common Maritime Data Structure (CMDS). Utilizing this common understanding of key players in e-Navigation arena, the IMO e-Navigation Correspondence Group has firmed up the overarching architecture, enabling a series to test beds proving the concept of integration of various data streams to enable improved communication between the stakeholders on shore or at sea. The integration of pre-composed, expert generated navigational data with real time and semi real-time data like Virtual AtoNs, Tide Gages Data or MSI transmission from VTS into a single e-Navigation display, if correctly developed, implemented and executed, will be the enabler of increased situational awareness.

A hallmark of tumor cell survival is the maintenance of elongated telomeres. It is known that antiviral reverse transcriptase inhibitors (RTIs) such as azidothymidine (AZT) and didanosine (ddI) lead to telomere shortening at high, potentially toxic concentrations. We hypothesized that those drugs might have synergistic effects enabling successful therapy with low, nontoxic concentrations. Biologic effects of AZT and ddI were analyzed at concentrations that correspond to minimal plasma levels achieved during human immunodeficiency virus therapy. Long-term coapplication of low-dose AZT and ddI induced a significant shortening of telomeres in the tumor cell lines HCT-116, SkMel-28, MelJuso, and Jurkat. Treatment of cells with both RTI, but not with single RTI, led to a significant accumulation of γH2AX, to p53 phosphorylation, and to cell apoptosis in all cell lines. Oral low-dose dual RTI application but not low-dose single RTI application was associated with a significantly reduced tumor growth of HCT-116 cells in mice. This antiproliferative activity of the combined use of AZT and ddI at low, clinically applicable concentrations warrants clinical testing in human solid cancer.