Towards Reuse on the Meta-Level

Modern software development peaks in complex product lines and utilizes features of programming languages to their extend. On the other hand, model driven development shines by abstraction from implementation details to ease communication between programmers and domain experts. With the CINCO meta tooling suite there is now a framework to factor out programming knowledge completely in that it allows creating domain specific graphical modeling environments. Bundled with capabilities of full code generation domain experts can create software with minimum effort. In this paper an extension to the language family of CINCO is introduced which acts as one part of a foundation for developing software product lines. It highly stretches reuse of model specifications to overcome reoccurring problems in the context of inter-model references

Evaluating selection bias in a population-based cohort study with low baseline participation: the LIFE-Adult-Study

Background: Participation in epidemiologic studies is steadily declining, which may result in selection bias. It is therefore an ongoing challenge to clarify the determinants of participation to judge possible selection effects and to derive measures to minimise that bias. We evaluated the potential for selection bias in a recent population-based cohort study with low baseline participation and investigated reasons for nonparticipation. Methods: LIFE-Adult is a cohort study in the general population of the city of Leipzig (Germany) designed to gain insights into the distribution and development of civilisation diseases. Nine thousand one hundred forty-five participants aged 40–79 years were randomly sampled in 2011–2014. We compared LIFE-Adult participants with both the Leipzig population and nonparticipants using official statistics and short questionnaire data. We applied descriptive statistics and logistic regression analysis to evaluate the determinants of study participation. Results: Thirty-one percent of the invited persons participated in the LIFE-Adult baseline examination. Study participants were less often elderly women and more often married, highly educated, employed, and current nonsmokers compared to both the Leipzig population and nonparticipants. They further reported better health than nonparticipants. The observed differences were considerable in education and health variables. They were generally stronger in men than in women. For example, in male study participants aged 50–69, the frequency of high education was 1.5 times that of the general population, and the frequency of myocardial infarction was half that of nonparticipants. Lack of time and interest, as well as health problems were the main reasons for nonparticipation. Conclusions: Our investigation suggests that the low baseline participation in LIFE-Adult is associated with the typical selection of study participants with higher social status and healthier lifestyle, and additionally less disease. Notably, education and health status seem to be crucial selection factors. Consequently, frequencies of major health conditions in the general population will likely be underestimated. A differential selection related to sex might also distort effect estimates. The extent of the assessment, the interest in the research topic, and health problems of potential participants should in future be considered in LIFE-Adult and in similar studies to raise participation and to minimise selection bias

Investigation of Cytotoxic T Lymphocyte Function during Allorejection in the Anterior Chamber of the Eye

Cytotoxic T lymphocytes (CTL) are an essential part of our immune system by killing infected and malignant cells. To fully understand this process, it is necessary to study CTL function in the physiological setting of a living organism to account for their interplay with other immune cells like CD4+ T helper cells and macrophages. The anterior chamber of the eye (ACE), originally developed for diabetes research, is ideally suited for non-invasive and longitudinal in vivo imaging. We take advantage of the ACE window to observe immune responses, particularly allorejection of islets of Langerhans cells by CTLs. We follow the onset of the rejection after vascularization on islets until the end of the rejection process for about a month by repetitive two-photon microscopy. We find that CTLs show reduced migration on allogeneic islets in vivo compared to in vitro data, indicating CTL activation. Interestingly, the temporal infiltration pattern of T cells during rejection is precisely regulated, showing enrichment of CD4+ T helper cells on the islets before arrival of CD8+ CTLs. The adaptation of the ACE to immune responses enables the examination of the mechanism and regulation of CTL-mediated killing in vivo and to further investigate the killing in gene-deficient mice that resemble severe human immune diseases

Diversity, population structure and palaeoecology of the Pleistocene large cervids from the Padang Highlands, Sumatra

This chapter deals with the dentognathic remains of the Late Pleistocene large cervids from the Padang Highlands caves in Sumatra. We used linear and geometric morphometric techniques to investigate variation, taxonomic position and body size trends in a dataset of upper and lower molars. Dental mesowear was used to assess dietary preference in a subsample. The results suggest the Padang Highlands cervids belonged to multiple populations of an early stock of Rusa deer the size of sambar (Rusa unicolor), but morphologically reminiscent of Javan rusa (Rusa timorensis). The Rusa sp. of Sumatra was reconstructed as a mixed feeder with an increase in the grazing component with age

MicroRNA expression after ionizing radiation in human endothelial cells

<p>Abstract</p> <p>Background</p> <p>Endothelial cells (EC) in tumor and normal tissue constitute critical radiotherapy targets. MicroRNAs have emerged as master switchers of the cellular transcriptome. Here, we seek to investigate the role of miRNAs in primary human dermal microvascular endothelial cells (HDMEC) after ionizing radiation.</p> <p>Methods</p> <p>The microRNA status in HDMEC after 2 Gy radiation treatment was measured using oligo-microarrays covering 361 miRNAs. To functionally analyze the role of radiation-induced differentially regulated miRNAs, cells were transfected with miRNA precursor or inhibitor constructs. Clonogenic survival and proliferation assays were performed.</p> <p>Results</p> <p>Radiation up-regulated miRNA expression levels included let-7g, miR-16, miR-20a, miR-21 and miR-29c, while miR-18a, miR-125a, miR-127, miR-148b, miR-189 and miR-503 were down-regulated. We found that overexpression or inhibition of let-7g, miR-189, and miR-20a markedly influenced clonogenic survival and cell proliferation per se. Notably, the radiosensitivity of HDMEC was significantly influenced by differential expression of miR-125a, -127, -189, and let-7g. While miR-125a and miR-189 had a radioprotective effect, miR-127 and let-7g enhanced radiosensitivity in human endothelial cells.</p> <p>Conclusion</p> <p>Our data show that ionizing radiation changes microRNA levels in human endothelial cells and, moreover, exerts biological effects on cell growth and clonogenicity as validated in functional assays. The data also suggest that the miRNAs which are differentially expressed after radiation modulate the intrinsic radiosensitivity of endothelial cells in subsequent irradiations. This indicates that miRNAs are part of the innate response mechanism of the endothelium to radiation.</p

Associations between anxiety, body mass index, and sex hormones in women

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group

Mental Health in Times of the COVID-19 Pandemic

The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria ( COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health.Peer Reviewe

Current Knowledge and Implications From a European Perspective

The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria (COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health

Glutamate-induced depression of EPSP–spike coupling in rat hippocampal CA1 neurons and modulation by adenosine receptors

The presence of high concentrations of glutamate in the extracellular fluid following brain trauma or ischaemia may contribute substantially to subsequent impairments of neuronal function. In this study, glutamate was applied to hippocampal slices for several minutes, producing over-depolarization, which was reflected in an initial loss of evoked population potential size in the CA1 region. Orthodromic population spikes recovered only partially over the following 60 min, whereas antidromic spikes and excitatory postsynaptic potentials (EPSPs) showed greater recovery, implying a change in EPSP–spike coupling (E–S coupling), which was confirmed by intracellular recording from CA1 pyramidal cells. The recovery of EPSPs was enhanced further by dizocilpine, suggesting that the long-lasting glutamate-induced change in E–S coupling involves NMDA receptors. This was supported by experiments showing that when isolated NMDA-receptor-mediated EPSPs were studied in isolation, there was only partial recovery following glutamate, unlike the composite EPSPs. The recovery of orthodromic population spikes and NMDA-receptor-mediated EPSPs following glutamate was enhanced by the adenosine A1 receptor blocker DPCPX, the A2A receptor antagonist SCH58261 or adenosine deaminase, associated with a loss of restoration to normal of the glutamate-induced E–S depression. The results indicate that the long-lasting depression of neuronal excitability following recovery from glutamate is associated with a depression of E–S coupling. This effect is partly dependent on activation of NMDA receptors, which modify adenosine release or the sensitivity of adenosine receptors. The results may have implications for the use of A1 and A2A receptor ligands as cognitive enhancers or neuroprotectants

Same brain, different look? The impact of scanner, sequence and preprocessing on diffusion imaging outcome parameters

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from, e.g., diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19–54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyrafit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps, obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability