Emulating Dendritic Computing Paradigms on Analog Neuromorphic Hardware

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The role of cellular prion protein in lipid metabolism in the liver

Cellular prion protein (PrPC) is a plasma membrane glycophosphatidylinositol-anchored proteinand it is involved in multiple functions, including neuroprotection and oxidative stress. So far,most of the PrPC functional research is done in neuronal tissue or cell lines; the role of PrPC innon-neuronal tissues such as liver is only poorly understood. To characterize the role of PrPC inthe liver, a proteomics approach was applied in the liver tissue of PrPC knockout mice. Theproteome analysis and biochemical validations showed an excessive fat accumulation in the liverof PrPC knockout mice with a change in mRNA expression of genes linked to lipid metabolism. Inaddition, the higher Bax to Bcl2 ratio, up-regulation of tgfb1 mRNA expression in PrPC knockoutmice liver, further showed the evidences of metabolic disease. Over-expression of PrPC in fattyacid-treated AML12 hepatic cell line caused a reduction in excessive intracellular fat accumulation;shows association of PrPC levels and lipid metabolism. Therefore, based on observation ofexcessive fat globules in the liver of ageing PrPC knockout mice and the reduction of fataccumulation in AML12 cell line with PrPC over-expression, the role of PrPC in lipid metabolismis described.Open-Access-Publikationsfonds 2020peerReviewe

Factorial Structure and Validity of Depression (PHQ-9) and Anxiety (GAD-7) Scales after Traumatic Brain Injury

Background: The dimensionality of depression and anxiety instruments have recently been a source of controversy. Objectives and Design: in a European-wide sample of patients after Traumatic Brain Injury (TBI), we aim to examine the factorial structure, validity, and association of the Patient Health Questionnaire for depression (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) instruments. This study is based on longitudinal observational data. We conducted analyses of factorial structure and discriminant validity of outcomes six-months after TBI. We also examined the prevalence, co-occurrence, and changes of scores on the PHQ-9 and GAD-7 at 3-, 6-, and 12-month post-TBI assessments. Participants: At six-months post-TBI assessment, 2137 (738 (34.5%) women) participants completed the PHQ-9 and GAD-7 questionnaires. For the longitudinal analysis, we had 1922 participants (672 (35.0%) women). Results: The results of exploratory factor analysis suggested a general latent construct underlying both PHQ-9 and GAD-7 measures. Confirmatory factor analyses showed a slight improvement in the fit indices for the bifactorial model. The Omega hierarchical test clearly di erentiated two subfactors of PHQ-9 and GAD-7 items over and above the underlying general factor; however, most of the variance (85.0%) was explained by the general factor and the explained variance of the subfactors was small. The PHQ-9 and GAD-7 performed similarly in detecting post-traumatic stress disorder (PTSD). As defined by conventional cut-o s, depression and anxiety have di erent prevalence rates in the sample. The scales also di ered in their relationships with the short form of health survey (SF-36v2) subscales. The longitudinal analysis showed high stability of depression and anxiety symptoms: 49–67% of the post-TBI patients with comorbid depression and anxiety reported the persistence of the symptoms over time. Discussion: The factorial structure analysis favors a general latent construct underlying both depression and anxiety scales among patients after TBI. We discuss the implications our findings and future research directions.Open-Access-Publikationsfonds 2020peerReviewe

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study

Aims: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. Methods and results: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class <III, and chronic obstructive pulmonary disease. Adjusted mortality associated with ICD vs. control was 27% lower (HR 0.731, 95% CI 0.569–0.938, P = 0.0140). Subgroup analyses indicated no ICD benefit in diabetics (adjusted HR = 0.945, P = 0.7797, P for interaction = 0.0887) or those aged ≥75 years (adjusted HR 1.063, P = 0.8206, P for interaction = 0.0902). Conclusion: In contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics.peerReviewe

Reference Values of the QOLIBRI from General Population Samples in the United Kingdom and The Netherlands

The Quality of Life after Traumatic Brain Injury (QOLIBRI) instrument is an internationally validated patient-reported outcome measure for assessing disease-specific health-related quality of life (HRQoL) in individuals after traumatic brain injury (TBI). However, no reference values for general populations are available yet for use in clinical practice and research in the field of TBI. The aim of the present study was, therefore, to establish these reference values for the United Kingdom (UK) and the Netherlands (NL). For this purpose, an online survey with a reworded version of the QOLIBRI for general populations was used to collect data on 4403 individuals in the UK and 3399 in the NL. This QOLIBRI version was validated by inspecting descriptive statistics, psychometric criteria, and comparability of the translations to the original version. In particular, measurement invariance (MI) was tested to examine whether the items of the instrument were understood in the same way by different individuals in the general population samples and in the TBI sample across the two countries, which is necessary in order to establish reference values. In the general population samples, the reworded QOLIBRI displayed good psychometric properties, including MI across countries and in the non-TBI and TBI samples. Therefore, differences in the QOLIBRI scores can be attributed to real differences in HRQoL. Individuals with and without a chronic health condition did differ significantly, with the latter reporting lower HRQoL. In conclusion, we provided reference values for healthy individuals and individuals with at least one chronic condition from general population samples in the UK and the NL. These can be used in the interpretation of disease-specific HRQoL assessments after TBI applying the QOLIBRI on the individual level in clinical as well as research contexts.Open-Access-Publikationsfonds 2020peerReviewe

Authigenic formation of Ca-Mg carbonates in the shallow alkaline Lake Neusiedl, Austria

Despite advances regarding the microbial and organic-molecular impact on nucleation, the formation of dolomite in sedimentary environments is still incompletely understood. Since 1960, apparent dolomite formation has been reported from mud sediments of the shallow, oligohaline and alkaline Lake Neusiedl, Austria. To trace potential dolomite formation or diagenetic alteration processes in its deposits, lake water samples and sediment cores were analyzed with respect to sediment composition, hydrochemistry and bacterial community composition. Sediments comprise 20 cm of homogenous mud with 60 wt % carbonate, which overlies dark-laminated consolidated mud containing 50 wt % carbonate and plant debris. Hydrochemical measurements reveal a shift from oxic lake water with pH 9.0 to anoxic sediment pore water with pH 7.5. A decrease in SO$_2^{−4}$ with a concomitant increase in ΣH$_2$S and NH$^+_4$ from 0 to 15 cm core depth indicates anaerobic heterotrophic decomposition, including sulfate reduction. The bacterial community composition reflects the zonation indicated by the pore water chemistry, with a distinct increase in fermentative taxa below 15 cm core depth. The water column is highly supersaturated with respect to (disordered) dolomite and calcite, whereas saturation indices of both minerals rapidly approach zero in the sediment. Notably, the relative proportions of different authigenic carbonate phases and their stoichiometric compositions remain constant with increasing core depth. Hence, evidence for Ca–Mg carbonate formation or ripening to dolomite is lacking within the sediment of Lake Neusiedl. As a consequence, precipitation of high-magnesium calcite (HMC) and protodolomite does not occur in association with anoxic sediment and sulfate-reducing conditions. Instead, analytical data for Lake Neusiedl suggest that authigenic HMC and protodolomite precipitate from the supersaturated, well-mixed aerobic water column. This observation supports an alternative concept to dolomite formation in anoxic sediments, comprising Ca–Mg carbonate precipitation in the water column under aerobic and alkaline conditions.Open-Access-Publikationsfonds 2020peerReviewe

The third person gap in adnominal pronoun constructions

The lack of third person adnominal pronouns in English-type languages (*they linguists) is argued to be an effect of contextually conditioned allomorphy between the exponents of the definite article and third person pronouns within a pronominal determiner structure. A crosslinguistic survey of 82 languages finds that the third person gap is crosslinguistically relatively rare and may be restricted to Europe and surrounding areas. The survey also suggests a potential interaction between the third person gap and the availability of distinct articles, as expected on the proposed analysis. The paper also discusses issues raised by the third person gap for alternative analyses, including those advocating an NP-analysis.Open-Access-Publikationsfonds 2020peerReviewe

Diverse Swards and Mixed-Grazing of Cattle and Sheep for Improved Productivity

Increasing sward phytodiversity has been suggested as having potential to increase primary production of grasslands, but whether any such gains are converted into secondary production, through improved performance of grazing livestock, remains uncertain. Animal production by cattle and sheep can also be enhanced by mixed-grazing. To our knowledge, this effect has never been studied in relation to differences in sward phytodiversity. Therefore, a rotational grazing experiment was conducted over 5 years (2007–2011) on permanent grassland in Germany using sheep and cattle in mono- (single-species) or mixed-grazing of swards differing in plant species richness. Herbicides against dicotyledonous plant species were used to create different sward types: species-poor, grass-dominated swards in contrast to untreated “diverse” control swards. We found no differences in herbage production between the sward types. However, compared to the grass-dominated sward, the diverse sward showed greater concentrations of crude protein and lower contents of acid detergent fiber in the herbage dry-matter. Lamb live weight gains were slightly greater on the diverse-swards (P < 0.05), but calf performance was unaffected by sward type. Mixed-grazing increased daily average live weight gains of suckler cows (g cow⁻¹ d⁻¹) (P < 0.05) as well as area-related daily live weight gains (kg ha⁻¹ d⁻¹) and total live weight gains (kg ha⁻¹) during the complete grazing season (P < 0.001). This indicates advantages of combining livestock species, attributed to complementary pasture use. We suggest that mixed-grazing of cattle and sheep on phytodiverse swards is an effective and sustainable means to enhance ecological and agronomic traits such as livestock production and plant species conservation. Lamb production especially showed benefits under mixed-grazing, with a 17% increase in live weight gain. Compared to the grass-dominated sward, diverse swards resulted in an average 12% increase of live weight gains (across grazing systems and livestock species).Open-Access-Publikationsfonds 2020peerReviewe

Influence of Sociodemographic, Premorbid, and Injury-Related Factors on Post-Concussion Symptoms after Traumatic Brain Injury

Background: Post-concussion symptoms (PCS) are often reported as consequences of mild and moderate traumatic brain injury (TBI), but these symptoms are not well documented in severe TBI. There is a lack of agreement as to which factors and covariates affect the occurrence, frequency, and intensity of PCS among TBI severity groups. The present study therefore aims to examine the association between sociodemographic, premorbid, and injury-related factors and PCS. Methods: A total of 1391 individuals (65% male) from the CENTER-TBI study were included in the analyses. The occurrence, frequency (number of PCS), and intensity (severity) of PCS were assessed using the Rivermead Post-concussion Symptoms Questionnaire (RPQ) at six months after TBI. To examine the association between selected factors (age, sex, living situation, employment status, educational background, injury and TBI severity, and premorbid problems) and PCS, a zero-inflated negative binomial model (ZINB) for occurrence and frequency of PCS and a standard negative binomial regression (NB) for intensity were applied. Results: Of the total sample, 72% of individuals after TBI reported suffering from some form of PCS, with fatigue being the most frequent among all TBI severity groups, followed by forgetfulness, and poor concentration. Different factors contributed to the probability of occurrence, frequency, and intensity of PCS. While the occurrence of PCS seemed to be independent of the age and sex of the individuals, both the frequency and intensity of PCS are associated with them. Both injury and TBI severity influence the occurrence and frequency of PCS, but are associated less with its intensity (except “acute” symptoms such as nausea, vomiting, and headaches). Analyses focusing on the mTBI subgroup only yielded results comparable to those of the total sample. Discussion: In line with previous studies, the results support a multifactorial etiology of PCS and show the importance of differentiating between their occurrence, frequency, and intensity to better provide appropriate treatment for individual subgroups with different symptoms (e.g., multiple PCS or more intense PCS). Although PCS often occur in mild to moderate TBI, individuals after severe TBI also suffer from PCS or post-concussion-like symptoms that require appropriate treatment. The chosen statistical approaches (i.e., ZINB and NB models) permit an ameliorated differentiation between outcomes (occurrence, frequency, and intensity of PCS) and should be used more widely in TBI research.Open-Access-Publikationsfonds 2020peerReviewe

Repeating noninvasive risk stratification improves prediction of outcome in ICD patients.

BACKGROUND: Noninvasive risk stratification aims to detect abnormalities in the pathophysiological mechanisms underlying ventricular arrhythmias. We studied the predictive value of repeating risk stratification in patients with an implantable cardioverter-defibrillator (ICD). METHODS: The EUTrigTreat clinical study was a prospective multicenter trial including ischemic and nonischemic cardiomyopathies and arrhythmogenic heart disease. Left ventricular ejection fraction ≤40% (LVEF), premature ventricular complexes >400/24 hr (PVC), non-negative microvolt T-wave alternans (MTWA), and abnormal heart rate turbulence (HRT) were considered high risk. Tests were repeated within 12 months after inclusion. Adjusted Cox regression analysis was performed for mortality and appropriate ICD shocks. RESULTS: In total, 635 patients had analyzable baseline data with a median follow-up of 4.4 years. Worsening of LVEF was associated with increased mortality (HR 3.59, 95% CI 1.17-11.04), as was consistent abnormal HRT (HR 8.34, 95%CI 1.06-65.54). HRT improvement was associated with improved survival when compared to consistent abnormal HRT (HR 0.10, 95%CI 0.01-0.82). For appropriate ICD shocks, a non-negative MTWA test or high PVC count at any moment was associated with increased arrhythmic risk independent of the evolution of test results (worsening: HR 3.76 (95%CI 1.43-9.88) and HR 2.50 (95%CI 1.15-5.46); improvement: HR 2.80 (95%CI 1.03-7.61) and HR 2.45 (95%CI 1.07-5.62); consistent: HR 2.47 (95%CI 0.95-6.45) and HR 2.40 (95%CI 1.33-4.33), respectively). LVEF improvement was associated with a lower arrhythmic risk (HR 0.34, 95%CI 0.12-0.94). CONCLUSIONS: Repeating LVEF and HRT improved the prediction of mortality, whereas stratification of ventricular arrhythmias may be improved by repeating LVEF measurements, MTWA and ECG Holter monitoring.peerReviewe