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At the onset of the COVID-19 pandemic, the Survey of Health, Ageing, and Retirement in Europe (SHARE) was in a unique position to respond to the need for high quality survey data on people's changing living situations. Implemented as two telephone interviews in the summer of 2020 and 2021 in 27 European countries and Israel, the SHARE Corona Surveys present a great advantage by their integration into the longitudinal, multidisciplinary and ex-ante harmonised design of the SHARE study. This allows researchers to trace changes from the pre-pandemic period, through the different stages of the pandemic, and the postpandemic situation. This article lays out the research aims and how the two Corona Surveys fit in the general design of SHARE. It presents the main design features of the SHARE Corona Surveys following the survey life cycle. It starts with information on procurement, contracting, funding, ethics, and data protection and sampling, followed by information on instrument design, translations, questionnaire content and interviewer training. Last, fieldwork, panel care and data processing are described. Focused on topics of health behaviour, health care, economics and social relationships, the balanced panel sample of the two SHARE Corona Surveys comprises more than 48,000 interviews and provides valuable information on how the 50+ population coped with the COVID-19 pandemic. The experience of implementing the SHARE Corona Surveys also offers insights into use of agile project management methods for large survey infrastructures and moving towards a multi-mode design in an ongoing panel data collection project. [ABSTRACT FROM AUTHOR]

Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns. Results: The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking. Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients. [ABSTRACT FROM AUTHOR]

Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is still undefined. Here, using integrated gene expression analysis and T cell receptor sequencing, we characterized γδ T cells in MSS CRC, with a focus on Vδ1 + T cells. We identified Vδ1+ T cells with shared motifs in the third complementarity-determining region of the δ-chain, reflective of antigen recognition. Changes in gene and protein expression levels suggested a dysfunctional effector state of Vδ1+ T cells in MSS CRC, distinct from Vδ1+ T cells in microsatellite-instable (MSI). Interaction analysis highlighted an immunosuppressive role of fibroblasts in the dysregulation of Vδ1+ T cells in MSS CRC via the TIGIT-NECTIN2 axis. Blocking this pathway with a TIGIT antibody partially restored cytotoxicity of the dysfunctional Vδ1 phenotype. These results define an operative pathway in γδ T cells in MSS CRC. Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is less well-studied. Here, using single-cell RNA-sequencing, the authors identify a Vδ1 + T cell subset, which are functionally impaired in MSS CRC via a TIGIT-NECTIN2 interaction. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) is a promising alternative to antibiotics and chemical substances in dentistry that can reduce the risk of unwanted side effects and bacterial resistance. AmbiJet is a device that can ignite and deliver plasma directly to the site of action for maximum effectiveness. The aim of the study was to investigate its antimicrobial efficacy and the possible development of bacterial resistance. The antimicrobial effect of the plasma was tested under aerobic and anaerobic conditions on bacteria (five aerobic, three anaerobic (Gram +/−)) that are relevant in dentistry. The application times varied from 1 to 7 min. Possible bacterial resistance was evaluated by repeated plasma applications (10 times in 50 days). A possible increase in temperature was measured. Plasma effectively killed 106 seeded aerobic and anaerobic bacteria after an application time of 1 min per 10 mm2. Neither the development of resistance nor an increase in temperature above 40 °C was observed, so patient discomfort can be ruled out. The plasma treatment proved to be effective under anaerobic conditions, so the influence of ROS can be questioned. Our results show that AmbiJet efficiently eliminates pathogenic oral bacteria. Therefore, it can be advocated for clinical therapeutic use. [ABSTRACT FROM AUTHOR]

We present results of implicit large eddy simulation (LES) and different Reynolds-averaged Navier–Stokes (RANS) models of the MTU 161 low pressure turbine at an exit Reynolds number of 90 000 and exit Mach number of 0.6. The LES results are based on a high-order discontinuous Galerkin method and the RANS is computed using a classical finite-volume approach. The paper discusses the steps taken to create realistic inflow boundary conditions in terms of end wall boundary layer thickness and freestream turbulence intensity. This is achieved by tailoring the input distribution of total pressure and temperature, Reynolds stresses and turbulence length scale to a Fourier series based synthetic turbulence generator. With this procedure, excellent agreement with the experiment can be achieved in terms of blade loading at midspan and wake total pressure losses at midspan and over the channel height. Based on the validated setup, we focus on the discussion of secondary flow structures emerging due to the interaction of the incoming boundary layer and the turbine blade and compare the LES to two commonly used RANS models. Since we are able to create consistent setups for both LES and RANS, all discrepancies can be directly attributed to physical modelling problems. We show that both a linear eddy viscosity model and a differential Reynolds stress model coupled with a state-of-the-art correlation-based transition model fail, in this case, to predict the separation induced transition process around midspan. Moreover, their prediction of secondary flow losses leaves room for improvement as shown by a detailed discussion of turbulence kinetic energy and anisotropy fields. [ABSTRACT FROM AUTHOR]

The eighth wave of the Survey of Health, Aging and Retirement in Europe comprises a subsample of respondents who were asked to participate in a measurement of physical activity using thigh-worn accelerometers. This paper describes the process for obtaining consent, identifies determinants of consent, and analyzes the aggregated results of the accelerometer measurements for bias due to sample selection. The overall consent rate in the Survey of Health, Aging and Retirement in Europe accelerometer study was 54%, with variations between countries ranging from 34% to 70%. Multivariate logistic regressions show that various factors are correlated with consent such as respondents' age, self-reported moderate activity, computer literacy, willingness to answer questions, and the interviewers' age. After introducing inverse probability weights, there appears to be only a small and insignificant influence of participant selection and consent. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic began impacting Europe in early 2020, posing significant challenges for individuals requiring care. This group is particularly susceptible to severe COVID-19 infections and depends on regular health care services. In this article, we examine the situation of European care recipients aged 50 years and older 18 months after the pandemic outbreak and compare it to the initial phase of the pandemic. In the descriptive section, we illustrate the development of (unmet) care needs and access to health care throughout the pandemic. Additionally, we explore regional variations in health care receipt across Europe. In the analytical section, we shed light on the mid- and long-term health consequences of COVID-19-related restrictions on accessing health care services by making comparisons between care recipients and individuals without care needs. We conducted an analysis using data from the representative Corona Surveys of the Survey of Health, Ageing and Retirement in Europe (SHARE). Our study examines changes in approximately 3,400 care-dependent older Europeans (aged 50+) interviewed in 2020 and 2021, comparing them with more than 45,000 respondents not receiving care. The dataset provides a cross-national perspective on care recipients across 27 European countries and Israel. Our findings reveal that in 2021, compared to the previous year, difficulties in obtaining personal care from someone outside the household were significantly reduced in Western and Southern European countries. Access to health care services improved over the course of the pandemic, particularly with respect to medical treatments and appointments that had been canceled by health care institutions. However, even 18 months after the COVID-19 outbreak, a considerable number of treatments had been postponed either by respondents themselves or by health care institutions. These delayed medical treatments had adverse effects on the physical and mental health of both care receivers and individuals who did not rely on care. [ABSTRACT FROM AUTHOR]

Orbital exenteration of periocular tumors complicated by orbital invasion is a heavy burden for patients and leads to disfiguring cosmesis and loss of vision. Here, we report our experience with globe-sparing surgery in a series of patients with periocular malignancies other than basal cell carcinoma (BCC), all exhibiting anterior orbital invasion. In this consecutive case series, we examined medical records of all patients between 2000 and 2018 with periocular malignancies (other than BCC) invading the anterior orbit (without extraocular muscle or scleral invasion) treated by one orbital surgeon (DP). The main outcome measures included local recurrence, regional and distant metastasis, survival, and visual acuity. Nine patients were identified. Of the non-BCC cancers invading the orbit, squamous cell carcinoma (SCC) (44.4%) was the most prevalent type in our series. Excision included the removal of visibly distinguishable tumor and a free clinical margin of up to 5 mm with histological confirmation of radicality of the invasive tumor component. Reconstruction was achieved by a variety of oculoplastic reconstructive procedures. At a mean follow-up of 70 months (range 11–177 months), 8 out of 9 patients were still alive. Recurrence occurred in two patients with conjunctival melanoma (CM), and they were again treated with wide excision. Postoperative visual acuity remained stable or improved. This retrospective case series demonstrates that globe-sparing excisional surgery can be considered in selected cases of periocular malignancies other than BCC with anterior orbital invasion, thus avoiding cosmetic disfigurement and loss of vision due to orbital exenteration. [ABSTRACT FROM AUTHOR]

These replies to critical comments by Elijah Chudnoff, Noah Lemos, and Kevin McCain on my book Radical Skepticism and Epistemic Intuition begin (after the Introduction) with Section 2, where I address a cluster of complaints from Chudnoff and McCain in connection with skepticism-supporting underdetermination principles. (These principles play a significant role in my portrayal of radical skepticism and in my Reidian response to it.) In Section 3, I reply to some objections from Lemos concerning a claim (from Radical Skepticism and Epistemic Intuition) that I call ' the Paradigm-case Thesis '. In Section 4, I respond to some concerns that McCain and Lemos raise in connection with my discussion of the rationality of seemings. Lastly, Section 5 covers a few remaining objections from McCain and Lemos having to do with Chisholm's "Problem of the Criterion," the comparative strength of seemings, and the challenge of identifying which seemings count as epistemic intuitions. [ABSTRACT FROM AUTHOR]

In this précis of Radical Skepticism and Epistemic Intuition , I highlight the main lines of argument in the book and provide an outline of each of the book's three parts. I explain how: Part I lays out an argument for radical skepticism and objects to one of the two main ways of responding to it; Part II presents my version of the other main way of responding to that skeptical argument (a version that relies heavily on epistemic intuition); and Part III defends epistemic intuition (and, thereby, my response to radical skepticism) from several important objections. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second deadliest cancer in the world. Besides APC and p53 alterations, the PI3K/AKT/MTOR and MAPK pathway are most commonly mutated in CRC. So far, no treatment options targeting these pathways are available in routine clinics for CRC patients. We systematically analyzed the response of CRC cells to the combination of small molecular inhibitors targeting the PI3K and MAPK pathways. We used CRC cells in 2D, 3D spheroid, collagen gel cultures and freshly isolated organoids for drug response studies. Readout for drug response was spheroid or organoid growth, spheroid outgrowth, metabolic activity, Western blotting and immunofluorescence. We found profound tumor cell destruction under treatment with a combination of Torin 1 (inhibiting mTOR), MK2206 (targeting AKT) and selumetinib (inhibiting MEK) in 3D but not in 2D. Induction of cell death was due to apoptosis. Western blot analysis revealed efficient drug action. Gedatolisib, a dual PI3K/mTOR inhibitor, could replace Torin1/MK2206 with similar efficiency. The presence of PI3K and/or RAS-RAF-MAPK pathway mutations accounted for treatment responsiveness. Here, we identified a novel, efficient therapy, which induced proliferation stop and tumor cell destruction in vitro based on the genetic background. These preclinical findings show promise to further test this combi-treatment in vivo in mice and to potentially develop a mutation specific targeted therapy for CRC patients. [ABSTRACT FROM AUTHOR]

Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this article reviews author's response to Jennifer Nagel's objections to their account of justification in relation to perceptual and epistemic beliefs. The author also defends their position that justification involves conscious mental states as evidence and addresses Nagel's alternative view that justification should be based on how things are in the world.

Despite wholeheartedly endorsing Lycan's commonsensism on display in On Evidence in Philosophy, this paper raises concerns about three views Lycan defends in that book. The first view is compatibilism about free will and determinism. The paper argues that Lycan's Moorean defense of compatibilism fails and that it is plausible for commonsensists to think that, in their dispute with incompatibilists, the burden of proof is on compatibilists. The second view is Lycan's Principle of Humility, offered as an account of the conditions under which recognized disagreement undermines knowledge. The paper considers a permissive and a demanding way of understanding his Principle of Humility and suggests that, contra Lycan, commonsensism fits better with a permissive understanding. The third view discussed is his coherentism about justification. The paper concludes that commonsensism is best understood in foundationalist terms and that Lycan's coherentism is, in fact, an inadequately motivated version of foundationalism. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers worldwide and demands more effective treatments. We sought to identify tumor selective CRC antigens and their therapeutic potential for cytotoxic T-cell targeting by transcriptomic and immunohistochemical analysis. LY6G6D was identified as a tumor selectively expressed CRC antigen, mainly in the microsatellite stable (MSS) subtype. A specific anti LY6G6D/CD3 T cell engager (TcE) was generated and demonstrated potent tumor cell killing and T cell activation in vitro. Ex vivo treatment of primary patient-derived CRC tumor slice cultures with the LY6G6D/CD3 TcE led to IFNgγ secretion in LY6G6D positive tumor samples. In vivo, LY6G6D/CD3 TcE monotherapy demonstrated tumor regressions in pre-clinical mouse models of engrafted human CRC tumor cells and PBMCs. Lastly, 2D and 3D cocultures of LY6G6D positive and negative cells were used to explore the bystander killing of LY6G6D negative cells after specific activation of T cells by LY6G6D positive cells. LY6G6D/CD3 TcE treatment was shown to lyse target negative cells in the vicinity of target positive cells through a combined effect of IFNgγ, TNFa and Fas/FasL. In summary, LY6G6D was identified as a selectively expressed CRC antigen that can be utilized to potently re-direct and activate cytotoxic T-cells to lyse LY6G6D expressing CRC using a TcE. This effect can be spread to target negative neighboring tumor cells, potentially leading to improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study is to evaluate local tumour control rates, radiation side‐effects, visual preservation and disease‐free survival (DFS) of uveal melanoma (UM) patients treated with fractionated stereotactic radiotherapy (fSRT). Methods: A retrospective study of UM patients, who were treated with fSRT (N = 189), was performed by the Rotterdam Ocular Melanoma Study group (ROMS), the Netherlands, between 1999 and 2014 with a follow‐up of at least 5 years. Results: The 1‐, 3‐, 5‐, 10‐ and 15‐year local tumour control rates were as follows: 99.4%, 92.8%, 92.2%, 89.3% and 89.3%, respectively. Cataract (67.8%) was the most common side‐effect of fSRT followed by retinopathy (35.1%), maculopathy (23.8%), vitreous haemorrhage (20.1%), neovascular glaucoma (NVG) (20.0%) and optic neuropathy (12.4%). Patients with anterior located UMs developed cataract more frequently (p = 0.047, multivariable analysis). By multivariable analysis, significant factors for secondary enucleation were tumour recurrence (p < 0.001) and NVG (p < 0.001). In multivariable analysis, risk factors for a worse DFS were larger UM (p = 0.024) and tumours with subretinal fluid (SRF) at baseline (p = 0.038). The 5‐year DFS was 77.0% and the best corrected visual acuity decreased significantly after treatment. After 5 years, 22.0% of patients and after 10 years 17.6% of patients had a visual acuity of ≤0.3 logMAR. Conclusion: Fractionated stereotactic radiotherapy is a good treatment option for small‐, medium‐ and large‐sized tumours with 5‐year local tumour control of 92.2%. After 5 years, 22.0% of the patients had a good vision. Independently of tumour location, the visual acuity decreased significantly after treatment. Overall, the 5‐year DFS was 77.0%. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic confronts governments and their health systems with great challenges for disease management. In many countries, hospitalization and in particular ICU occupancy is the primary measure for policy makers to decide on possible non-pharmaceutical interventions. In this paper a combined methodology for the prediction of COVID-19 case numbers, case-specific hospitalization and ICU admission rates as well as hospital and ICU occupancies is proposed. To this end, we employ differential flatness to provide estimates of the states of an epidemiological compartmental model and estimates of the unknown exogenous inputs driving its nonlinear dynamics. A main advantage of this method is that it requires the reported infection cases as the only data source. As vaccination rates and case-specific ICU rates are both strongly age-dependent, specifically an age-structured compartmental model is proposed to estimate and predict the spread of the epidemic across different age groups. By utilizing these predictions, case-specific hospitalization and case-specific ICU rates are subsequently estimated using deconvolution techniques. In an analysis of various countries we demonstrate how the methodology is able to produce real-time state estimates and hospital/ICU occupancy predictions for several weeks thus providing a sound basis for policy makers. [ABSTRACT FROM AUTHOR]

A hallmark of thoracic aortic aneurysms (TAA) is the degenerative remodeling of aortic wall, which leads to progressive aortic dilatation and resulting in an increased risk for aortic dissection or rupture. Telocytes (TCs), a distinct type of interstitial cells described in many tissues and organs, were recently observed in the aortic wall, and studies showed the potential regulation of smooth muscle cell (SMC) homeostasis by TC-released shed vesicles. The purpose of the present work was to study the functions of TCs in medial degeneration of TAA. During aneurysmal formation an increase of aortic TCs was identified in human surgical specimens of TAA-patients, compared to healthy thoracic aortic (HTA)-tissue. We found the presence of epithelial progenitor cells in the adventitial layer, which showed increased infiltration in TAA samples. For functional analysis, HTA- and TAA-telocytes were isolated, characterized, and compared by their protein levels, mRNA- and miRNA-expression profiles. We detected TC and TC-released exosomes near SMCs. TAA-TC-exosomes showed a significant increase of the SMC-related dedifferentiation markers KLF-4-, VEGF-A-, and PDGF-A-protein levels, as well as miRNA-expression levels of miR-146a, miR-221 and miR-222. SMCs treated with TAA-TC-exosomes developed a dedifferentiation-phenotype. In conclusion, the study shows for the first time that TCs are involved in development of TAA and could play a crucial role in SMC phenotype switching by release of extracellular vesicles. [ABSTRACT FROM AUTHOR]

The article addresses under determination arguments for radical scepticism, presents non-inferential anti-skeptical responses, and addresses skeptical challenges to epistemic intuition. The narrative unfolds by highlighting the failure of inferential anti-skeptical responses, advocating for non-inferential anti-skepticism grounded in particularist epistemic intuitions and dismissing concerns about the reliability of epistemic intuition as a belief source.

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Telocytes (TCs), a novel interstitial cell entity promoting tissue regeneration, have been described in various tissues. Their role in inter-cellular signalling and tissue remodelling has been reported in almost all human tissues. This study hypothesizes that TC also contributes to tissue remodelling and regeneration of the human thoracic aorta (HTA). The understanding of tissue homeostasis and regenerative potential of the HTA is of high clinical interest as it plays a crucial role in pathogenesis from aortic dilatation to lethal dissection. Therefore, we obtained twenty-five aortic specimens of heart donors during transplantation. The presence of TCs was detected in different layers of aortic tissue and characterized by immunofluorescence and transmission electron microscopy. Further, we cultivated and isolated TCs in highly differentiated form identified by positive staining for CD34 and c-kit. Aortic-derived TC was characterized by the expression of PDGFR-a, PDGFR-ß, CD29/integrin ß-1 and aSMA and the stem cell markers Nanog and KLF-4. Moreover, TC exosomes were isolated and characterized for soluble angiogenic factors by Western blot. CD34+/c-kit+ TCs shed exosomes containing the soluble factors VEGF-A, KLF-4 and PDGF-A. In summary, TC occurs in the aortic wall. Correspondingly, exosomes, derived from aortic TCs, contain vasculogenesis-relevant proteins. Understanding the regulation of TC-mediated aortic remodelling may be a crucial step towards designing strategies to promote aortic repair and prevent adverse remodelling. [ABSTRACT FROM AUTHOR]

The currently ongoing COVID-19 pandemic confronts governments and their health systems with great challenges for disease management. Epidemiological models play a crucial role, thereby assisting policymakers to predict the future course of infections and hospitalizations. One difficulty with current models is the existence of exogenous and unmeasurable variables and their significant effect on the infection dynamics. In this paper, we show how a method from nonlinear control theory can complement common compartmental epidemiological models. As a result, one can estimate and predict these exogenous variables requiring the reported infection cases as the only data source. The method allows to investigate how the estimates of exogenous variables are influenced by non-pharmaceutical interventions and how imminent epidemic waves could already be predicted at an early stage. In this way, the concept can serve as an "epidemometer" and guide the optimal timing of interventions. Analyses of the COVID-19 epidemic in various countries demonstrate the feasibility and potential of the proposed approach. The generic character of the method allows for straightforward extension to different epidemiological models. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Robotic 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. Methods: All 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. Results: In 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). Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Background Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. Methods Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. Results No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. Conclusions Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence. [ABSTRACT FROM AUTHOR]

Objectives: Enteric and colonic sinus tracts are inflammatory complications that precede intestinal fistulas in patients with Crohn's disease (CD). The aim of this study was to retrospectively determine the prevalence, morphologic features, and outcome of sinus tracts using MR imaging.Methods: A consecutive cohort of 642 patients with known CD, referred for MR enterography or MR enteroclysis (study period 01/2014-09/2019), was evaluated retrospectively for the presence of sinus tracts, their locations, presence and length of coexisting strictures, bowel wall thickness, CDMI score, upstream dilation, and bowel distension. Clinical outcome was assessed using medical records. For metric data, means and standard deviation, as well as one-way ANOVA and Pearson's correlation coefficient, were calculated.Results: In 36/642 patients with CD undergoing MRE, 49 sinus tracts (forty in small intestine, nine in left-sided colon) were detected with a prevalence of 6.9% in patients with MR-visible signs of CD (n = 519, overall prevalence of 5.6%). Mean segmental bowel wall thickness was 8.9 mm, and mean CDMI score was 9.3. All sinus tracts were located within a stenotic segment, showing mesenteric orientation within the small bowel and upstream dilation in 13 patients. Of 36 patients, 19 underwent immediate surgery and seven developed clinical progression within the segment containing the sinus tract.Conclusions: Sinus tracts occur in 6.9% of patients with visible signs of CD. They are located within stenotic, severely thickened bowel segments with high MR inflammation scores. Their detection is clinically important, because they indicate a more aggressive phenotype and, if left untreated, may show severe progression.Key Points: • Sinus tracts occur in 6.9% of patients with MR-visible signs of Crohn's disease. • Sinus tracts are a radiological indicator of early penetrating Crohn's disease, with a high risk of progression, and require dedicated treatment. • Sinus tracts can be recognized by characteristic findings and typically occur in stenotic, severely thickened bowel segments with high MR inflammation scores. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the second most common cause of cancer‐related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I–IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography‐mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I–IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl‐alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression. What's new? Metabolomics is a sophisticated method for investigating whether the metabolite profile of a patient's blood, etc., may reflect the pathophysiological state of cancers and other diseases. In the present study, the authors analyzed circulating metabolites, seeking biomarkers related to colorectal cancer progression. Their results at various stages of colorectal cancer suggest that metabolic pathways involving citrulline, histidine, and other molecules that have been previously implicated in colorectal cancer development may also be linked to progression. [ABSTRACT FROM AUTHOR]

Guidelines for interviewers frequently include instructions to read question texts exactly as they are worded. Deviations from these guidelines on standardized interviewing might affect the comparability of survey answers and impair the quality of data. This paper contributes to the literature on interviewer behavior by analyzing how interviewers change their reading behavior during fieldwork and whether this behavioral change influences the response behavior of survey respondents. We use item-level paradata from the Survey of Health, Ageing and Retirement in Europe (SHARE) to measure interviewers' reading times and focus our analyses on introductory questions that do not require an immediate response by the respondent. In contrast to prior research, this focus enables us to disentangle the reading times of interviewers from the response times of respondents. Based on fixed effects regression, our results show systematic changes in interviewers' reading times of introductory items: First, reading times significantly decrease over the survey's field period, even after controlling for relevant respondent characteristics and specific aspects of the interview situation. Second, a cross-national comparison, including fourteen European countries plus Israel, reveals that the decrease is uniform in almost all countries, suggesting its generalizability across different cultural contexts. Third, the decrease in reading times influences response behavior to varying degrees. Response behavior is affected if introductions contain relevant information for understanding or fulfilling the required task and especially if the response refers to within-survey requests. On the basis of these findings, we discuss the possible consequences for questionnaire design, interviewer training, and fieldwork monitoring. [ABSTRACT FROM AUTHOR]

We demonstrate a thin-film flip-chip (TFFC) light-emitting diode (LED) emitting in the ultraviolet B (UVB) at 311 nm, where substrate removal has been achieved by electrochemical etching of a sacrificial Al 0.37 Ga 0.63 N layer. The electroluminescence spectrum of the TFFC LED corresponds well to the as-grown LED structure, showing no sign of degradation of structural and optical properties by electrochemical etching. This is achieved by a proper epitaxial design of the sacrificial layer and the etch stop layers in relation to the LED structure and the electrochemical etch conditions. Enabling a TFFC UV LED is an important step toward improving the light extraction efficiency that limits the power conversion efficiency in AlGaN-based LEDs. [ABSTRACT FROM AUTHOR]

In this study, an atmospheric nitrogen plasma jet generated by a custom-built micro-plasma device was analyzed at room temperature by continuous wave and pulse EPR spectroscopy in real time. Transiently formed nitrogen atoms were detected without the necessity to use spin-traps or other reagents for their stabilization. In contrast to results from optical emission spectroscopy, only signals from the 4S ground state of 14N and 15N could be detected. EPR data analysis revealed an isotropic g value of 1.9971 and isotropic hyperfine coupling constants of a(14N) = (10.47 ± 0.02) MHz and a(15N) = (14.69 ± 0.02) MHz. Moreover, lifetime and relaxation data could be determined; both are discussed in terms of spectral widths and actual concentrations of the transiently formed nitrogen species within the plasma jet. The data show that the lifetimes of atomic nitrogen and charged particles such as N+ must be different, and for the latter below the observation time window of EPR spectroscopy. We demonstrate that the real-time (pulsed) EPR technique is a fast and reliable alternative to detect atomic nitrogen in atmospheric pressure plasma jets. The method may be used for a continuous monitoring of the quality of plasma jets. [ABSTRACT FROM AUTHOR]

Summary: Background: The rate of restoration of intestinal continuity after colonic resection and stoma creation in patients with Crohn's disease has not been well-documented in the era of biologics. Thus, the incidence of restoration of intestinal continuity since the introduction of biological drugs was assessed. Methods: Consecutive patients (n = 43) who underwent colonic resection with ileostomy or colostomy formation for Crohn's disease at a single tertiary referral center between 2002 and 2014 were identified. Data from individual chart review were analyzed retrospectively. Patients were personally contacted for follow-up. Results: Of the 43 patients 8 (18.4%) had a proctectomy leaving 35 patients (81.4%) with the rectum preserved. Of the 30 patients qualifying for final analysis restoration of bowel continuity was finally achieved in 10 patients (33.3%). Permanent stoma rates were comparable in the group of patients with and without biological therapy after surgery (64.3% vs. 60%). The median follow-up period was 7 years (range 3–15 years). Of the patients 20 suffered from perianal disease involvement (66.7%), which was associated with a higher rate of permanent stoma (n = 16/20, 80%) in contrast to patients without perianal disease (n = 4/10, 40%, p = 0.045). Conclusion: The overall incidence of stoma formation was low for patients with Crohn's disease; however, once a stoma is created the chance of ending up with a permanent stoma is high even in the era of biologics. Despite the use of new therapeutic agents perianal disease increases the risk of a permanent stoma. [ABSTRACT FROM AUTHOR]

Heterogeneously integrated AlGaN epitaxial layers will be essential for future optical and electrical devices like thin-film flip-chip ultraviolet (UV) light-emitting diodes, UV vertical-cavity surface-emitting lasers, and high-electron mobility transistors on efficient heat sinks. Such AlGaN-membranes will also enable flexible and micromechanical devices. However, to develop a method to separate the AlGaN-device membranes from the substrate has proven to be challenging, in particular, for high-quality device materials, which require the use of a lattice-matched AlGaN sacrificial layer. We demonstrate an electrochemical etching method by which it is possible to achieve complete lateral etching of an AlGaN sacrificial layer with up to 50% Al-content. The influence of etching voltage and the Al-content of the sacrificial layer on the etching process is investigated. The etched N-polar surface shows the same macroscopic topography as that of the as-grown epitaxial structure, and the root-mean square roughness is 3.5 nm for 1 μ m × 1 μ m scan areas. Separated device layers have a well-defined thickness and smooth etched surfaces. Transferred multi-quantum-well structures were fabricated and investigated by time-resolved photoluminescence measurements. The quantum wells showed no sign of degradation caused by the thin-film process. [ABSTRACT FROM AUTHOR]

The fabrication of an entire interview, is a rare event in the Survey of Health, Ageing and Retirement in Europe (SHARE) but can nevertheless lead to negative consequences regarding the panel sample, such as a loss in sample size or the need for time-consuming data corrections of information collected in previous waves. The work presented in this article started with the discovery of a case of interviewer fabrication after fieldwork for the sixth wave of SHARE was completed. As a consequence, we developed a technical procedure to identify interview fabrication and deal with it during ongoing fieldwork in the seventh wave. Unlike previous work that often used small experimental datasets and/or only a few variables to identify fake interviews, we implemented a more complex approach with a multivariate cluster analysis using many indicators from the available CAPI data and paradata. Analyses with the known outcome (interview fabrication or not) in wave 6 revealed that we were able to correctly identify a large number of the truly faked interviews while keeping the rate of 'false alarms' rather low. With these promising results, we started using the same script during the fieldwork for wave 7. We provided the survey agencies with information for targeted (instead of random) back checks to increase the likelihood of confirming our initial suspicion. The results show that only a very small number of interview fabrications could be unequivocally identified. [ABSTRACT FROM AUTHOR]

Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records. What's new? Colorectal cancer exhibits certain characteristic changes in metabolic pathways. To expand upon previous findings, these authors performed a discovery‐replication study using two large independent study populations from different countries, Germany and Austria. They tested metabolic profiles of cancer patients and controls, identifying 691 statistically significant features in the discovery cohort. Testing the second cohort narrowed it to 97. These corresponded to 28 metabolites, of which 15 could be identified. It will be useful to go forward with prospective analysis on these 15 metabolites, to determine whether they have predictive or prognostic value. [ABSTRACT FROM AUTHOR]

Background: Recent studies support the use of mechanical bowel preparation and/or oral antibiotic prophylaxis in patients operated on for Crohn's disease (CD); however, data are scarce, especially for laparoscopic surgery. Therefore, this study was carried out to investigate the effect of laparoscopic surgery on complication rates in patients not undergoing standardized bowel preparation but single shot antibiotics.Methods: In this study 255 consecutive patients who underwent a laparoscopic intestinal resection for CD at a tertiary referral center between 1997 and 2014 were retrospectively analyzed. Superficial surgical site infections (SSI), organ/space infections and ileus were recorded and grouped according to the type of resection (colorectal vs. small intestine ± ileocecal).Results: The baseline characteristics of the groups were comparable. Colorectal resections showed a significantly increased risk of organ/space infection (4.6% in small intestine ± ileocecal vs. 14.3% in colorectal resections p = 0.039). The superficial SSI rate was low in both groups (1.8% in small intestine ± ileocecal resection vs. 0% in colorectal resections, p = 1.000). Univariate binary logistic regression analysis revealed a statistically significant influence of duration of surgery (p = 0.001) and type of resection (p = 0.031) on organ/space infection. In multivariate analysis, only duration of surgery (OR 1.111, 95% CI 1.026-1.203 for every 10 min, p = 0.009) remained significant for postoperative organ/space infections.Conclusions: Single-shot antibiotic therapy without bowel preparation is safe in patients undergoing minimally invasive surgery and was associated with a low number of complications; however, organ/space infections were more common if colorectal resections were performed. Therefore, combined bowel preparation might be beneficial when the (sigmoid) colon or rectum are involved. [ABSTRACT FROM AUTHOR]

Purpose: Therapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance.Methods: In a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response. In vitro resistance models were created by exposing colorectal cancer cell lines to fractionated irradiation and selecting long-term survivors.Results: Our findings revealed significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies as well as in surgical specimens of non-responsive compared to responsive patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA expression in mismatch-incompetent DLD1 cells already after one dose of irradiation. Surviving clones after one or two series of radiation were more resistant to an additional radiation fraction than non-irradiated controls and showed a significant increase in expression of the FGF8 receptor FGFR3 and of Survivin on both the RNA and the protein levels.Conclusion: The results of this study suggest that FGF8 and Survivin contribute to radiation resistance in rectal cancer and may serve as markers to select patients who may not benefit from neoadjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: The long-acting muscarinic antagonist tiotropium bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler(®) (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat(®) Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of tiotropium delivered by Respimat is the closest match to tiotropium HandiHaler.Methods: Evaluation of six clinical trials (duration from 3 weeks to 2-3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes.Results: In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg).Conclusion: These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD.Funding: Boehringer Ingelheim. [ABSTRACT FROM AUTHOR]

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<0.001, OR 5.577) and the presence of an inflammatory mass (p = 0.003, OR 0.280). Conclusion: Δ albumin is a better prognostic marker for an eventful postoperative course after laparoscopic surgery in patients with Crohn’s disease in comparison to albumin alone. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The modified Glasgow prognostic score (mGPS) has recently gained increased attention as a prognostic marker for malignant disease survival and postoperative short-term complications. Due to lacking data, the present study was conducted to correlate the mGPS with the postoperative course in patients following surgery for Crohn’s disease.Methods: We enrolled 341 patients who underwent intestinal resection for symptomatic Crohn’s disease at a tertiary referral centre between 2000 and 2014. All relevant data were obtained from the institutional database and individual chart review. Thirty-day morbidity was defined according to the Clavien-Dindo classification.Results: A total of 79 (23.17%) postoperative complications were identified (grade I and II: n = 54, 15.84%; grade III and IV: n = 23, 6.74%; grade V: n = 2, 0.59%). The mGPS did not show any correlation with an eventful postoperative course following surgery (no complication: median mGPS: 1, range 0-2; complications: median mGPS: 1, range 0-2; p = 0.8521). In addition, the occurrence of an anastomotic leakage was not associated with a higher mGPS (p = 0.8592). Patients with an acute indication for surgery (n = 29, 11.44%) had higher median mGPS (median: 2, range 0-2) in contrast to patients who were operated on electively (median: 1, range 0-2; p = 0.0003). No other correlation between surgical characteristics and mGPS was detected.Conclusions: In the present study, we could clearly demonstrate that an acute indication for surgery in symptomatic Crohn’s disease is associated with higher mGPS scores. However, the mGPS did not correlate with postoperative complications. Further studies are required to define the prognostic value of mGPS in Crohn’s disease patients. [ABSTRACT FROM AUTHOR]

Based on the modal analysis method, we developed a model that describes the output beam of a diode‐pumped solid state (DPSS) laser emitting a multimode beam. Measuring the output beam profile in the near field and at the constructed far field the individual modes, their respective contributions, and their optical parameters are determined. Using this information, the beam is optically reshaped into a quasi‐Gaussian beam by the interference and superposition of the various modes. This process is controlled by a mode modulator unit that includes different meso‐aspheric elements and a soft‐aperture. The converted beam is guided into a second optical unit comprising achromatic‐aspheric elements to produce a thin light sheet for ultramicroscopy. We found that this light sheet is markedly thinner and exhibits less side shoulders compared with a light sheet directly generated from the output of a DPSS multimode laser. [ABSTRACT FROM AUTHOR]

Background: The Neutrophil-to-lymphocyte-ratio has recently gained increased attention as a prognostic marker for malignant disease and short term outcomes. There is little data available in patients with Crohn’s disease, thus the present study was conducted to correlate preoperative Neutrophil-to-lymphocyte-ratio values with disease phenotype and postoperative course.Methods: We comprised 373 patients, who underwent intestinal resection for symptomatic Crohn’s disease at an academic tertiary referral centre between 2000 and 2014. Preoperative Neutrophil-to-lymphocyte-ratio values were calculated and analyzed in regard to disease phenotype and 30-day morbidity rate. All relevant data were obtained from the institutional database and individual chart review.Results: Male patients had significantly higher preoperative Neutrophil-to-lymphocyte-ratio values compared to female patients (5 vs. 4; p = 0.0075). A higher Neutrophil-to-lymphocyte-ratio was also found in patients with an acute indication for surgery (6.15 vs. 4.3; p = 0.0374), presenting with abscesses (5.36 vs. 4.28; p = 0.0254), inflammatory masses (5.23 vs. 4.08; p = 0.0294) or malignancy in the resected specimen (9.06 vs. 4.35, p = 0.0231). Surprisingly, patients developing postsurgical complications showed significantly lower Neutrophil-to-lymphocyte-ratio values (3.77 vs. 4.67; p = 0.0461).Conclusions: Elevated preoperative Neutrophil-to-lymphocyte-ratio in symptomatic Crohn’s disease is not predictive for complications. However, Neutrophil-to-lymphocyte-ratio showed a significant correlation with specific disease phenotypes. Most strikingly, Neutrophil-to-lymphocyte-ratio was highly elevated in patients with a colorectal cancer in the resected specimen, which needs to be addressed in future studies. [ABSTRACT FROM AUTHOR]