Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Background Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results CSF NfL levels were significantly higher in patients with SD (median: 2326\u2009pg/mL, IQR: 1628\u20133593) than in controls (577 (446\u2013766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs = 120.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs = 120.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The development of a scale of the Guttman Type for the assessment of mobility disability in multiple sclerosis

Objective: The aim of the study was to develop a valid and reliable unidimensional scale of the Guttman type for the assessment of mobility disability in multiple sclerosis (MS). Subjects: Sixty-eight subjects with a definite diagnosis of MS participated.They were attending as outpatients at a MS unit at a District General Hospital. Thirty had the primary progressive pattern of disease, and 38 had the relapsing-remitting pattern. Methods: Formal assessments used for neurological disability were inspected, and 14 test items of gross motor function were extracted and ordered according to two criteria. These were that actions progressed from lying, to sitting, to standing and walking tasks, and that they progressed from broader to narrower bases of support. All subjects carried out all test items which were scored as ‘pass’ or ‘fail’. Analysis: Data were tested for internal consistency, reliability, inter item correlation, reproducibility and scalability. On the basis of the results, the items were re-ordered in rank, and reduced to eleven tests. The eleven item scale was re-analysed. Results: Results showed that the scale had an internal consistency of 0.88 (alpha coefficient) and a coefficient of reproducibility (CR) of 0.95 and above for both MS subject groups. The coefficient of scalability (CS) for items was 0.78 for primary progressive subjects and 0.74 for the relapsing-remitting group. Reliability ranged from good (kappa = 0.49) for one item, to perfect for six items. Conclusion: The scale was demonstrated to be a hierarchical scale of the Guttman type exhibiting homogeneous unidimensionality and good reliability. The high CR indicated that scores may be summed, and the very acceptable levels of CS indicated that the cumulative scores are meaningful within the defined concept of hierarchy used in this study

Zukunft der Arbeit und Arbeit der Zukunft in Deutschland

Due to the fact that the unemployment rate of high skilled labour in Germany is about 3% in the last 30 years, this paper deals with theories that account for heterogeneous labour. The main finding is that the reduction of the labour costs cannot reduce the aggregated unemployment rate substantially. An important conclusion is that the skill upgrading of the labour force is slower than that of labour demand. The future of work in Germany lies not in low paid low skilled jobs, but in high(er) skilled occupation. Copyright Verein für Socialpolitik und Blackwell Publishers Ltd, 2006

Confirmation of a highly dispersive dangling bond band on Ge(111)2x1

Submitted to Phys. Rev. Lett.Copy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman