Autosomal dominant Alzheimer disease: A unique resource to study CSF biomarker changes in preclinical AD

Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for Amyloid Precursor Protein (APP), Presenilin 1 (PSEN-1) and Presenilin 2 (PSEN-2) cause over-production of the amyloid-beta peptide (Abeta) leading to early deposition of Abeta in the brain, which in turn is hypothesized to initiate a cascade of processes resulting in neuronal death, cognitive decline and eventual dementia. Studies of cerebrospinal fluid (CSF) from individuals with the more common late-onset form of AD (LOAD) has revealed that low CSF Abeta42 and high CSF tau are associated with AD brain pathology. Herein we review the literature on CSF biomarkers in autosomal dominant AD (ADAD) which has contributed to a detailed road map of AD pathogenesis, especially during the preclinical period, prior to the appearance of any cognitive symptoms. Current drug trials are also taking advantage of the unique characteristics of ADAD and utilizing CSF biomarkers to accelerate development of effective therapies for AD

Unterschiedliche Bilanzierungsregeln in den USA und Europa: Welches ist die bessere Methode?

Angesichts der aktuellen US-amerikanischen Bilanzskandale erscheint die Bilanzierung nach US-GAAP den europäischen Regeln unterlegen. Nach Meinung von Dr. Joachim Schindler und Dr. Anne Schurbohm, KPMG, sind die Bilanzierungsstandards der US-GAAP nicht für eine weltweite Anwendung geeignet. Nach Ansicht von Prof. Dr. Jochen Zimmermann, Universität Bremen, steht dagegen bei einem Vergleich »das deutsche System der Rechnungslegung ... klar auf der Verliererseite«, während Prof. Dr. Hanno Merkt, Hochschule für Rechtswissenschaft, Hamburg, für ein »sowohl als auch« plädiert. Prof. Dr. Wolfgang Männel, Universität Erlangen-Nürnberg, stellt in seinem Beitrag vor allem die Unterschiede in der Rechnungslegung nach IAS und HGB heraus

Unterschiedliche Bilanzierungsregeln in den USA und Europa: Welches ist die bessere Methode?

Angesichts der aktuellen US-amerikanischen Bilanzskandale erscheint die Bilanzierung nach US-GAAP den europäischen Regeln unterlegen. Nach Meinung von Dr. Joachim Schindler und Dr. Anne Schurbohm, KPMG, sind die Bilanzierungsstandards der US-GAAP nicht für eine weltweite Anwendung geeignet. Nach Ansicht von Prof. Dr. Jochen Zimmermann, Universität Bremen, steht dagegen bei einem Vergleich »das deutsche System der Rechnungslegung ... klar auf der Verliererseite«, während Prof. Dr. Hanno Merkt, Hochschule für Rechtswissenschaft, Hamburg, für ein »sowohl als auch« plädiert. Prof. Dr. Wolfgang Männel, Universität Erlangen-Nürnberg, stellt in seinem Beitrag vor allem die Unterschiede in der Rechnungslegung nach IAS und HGB heraus.Bilanzierung, Bilanzrecht, Bilanzpolitik, Europa, Vereinigte Staaten

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolite

The digital transformation of knowledge order: a model for theanalysis of the epistemic crisis

In a proclaimed age of ‘post-truth,’ scholars have raised concerns about the spread of false information and the questioning of epistemic authorities. In this paper, we develop an analytical model to capture the digital transformation of knowledge order. Drawing on insights from social epistemology, sociology and history of knowledge, and media history, we identify epistemic practices as basic elements of knowledge order. We then analyze how epistemic practices are organized into an overarching structure of knowledge phases, contexts, roles, and hierarchies. Digital media tend to destabilize the traditional knowledge order. This destabilization is characterized by a more flexible order of phases, a dissolution of boundaries between contexts, an opening of professional roles to new actors, and a flattening of hierarchies

Paternal Values towards Women’s Empowerment and its Associations with Maternal and Paternal Antenatal Care Attendance among Sub–saharan African Population 2010-2014

Background & aim: Increased paternal engagement in antenatal care and birth positively influences pregnancy outcomes. There is very little research that describes the men's value of the reproductive health of their partner and its impact on paternal engagement in preconception, antenatal, and postpartum care. The purpose of this study was to examine the potential associations of paternal values towards women’s empowerment (PVWE) with maternal and paternal antenatal care (ANC) attendance.Methods: Secondary analysis of a men’s survey conducted by the Demographic and Health Surveys (2010-2014) (n=26892). A retrospective analysis of observational data collected as part of a prospective census survey was performed. An empowerment instrument was created ad hoc using four available variables. Nine sub-Saharan countries were included. Surveys obtained via stratified sampling with varying probability using weight distributions. Data were pooled into an aggregate dataset and examined through various regression methods. Results: PVWE was positively associated with maternal antenatal care. Lower PVWE was associated with lower likelihood that women attend ANC. PVWE was also positively associated with paternal antenatal care attendance. Lower versus higher PVWE was associated with lower likelihood that fathers attended ANC.Conclusion: PVWE is positively associated with maternal and paternal antenatal care attendance. Men’s values of the reproductive rights of their partner may contribute to antenatal care attendance or antenatal care may shape men’s values of women.  Further research can build upon this study to provide more insight as to how masculinity shapes men’s values of the respective rights of women

GPS driving: A digital biomarker for preclinical Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. Preclinical AD is the period during which early AD brain changes are present but cognitive symptoms have not yet manifest. The presence of AD brain changes can be ascertained by molecular biomarkers obtained via imaging and lumbar puncture. However, the use of these methods is limited by cost, acceptability, and availability. The preclinical stage of AD may have a subtle functional signature, which can impact complex behaviours such as driving. The objective of the present study was to evaluate the ability of in-vehicle GPS data loggers to distinguish cognitively normal older drivers with preclinical AD from those without preclinical AD using machine learning methods. METHODS: We followed naturalistic driving in cognitively normal older drivers for 1 year with a commercial in-vehicle GPS data logger. The cohort included n = 64 individuals with and n = 75 without preclinical AD, as determined by cerebrospinal fluid biomarkers. Four Random Forest (RF) models were trained to detect preclinical AD. RF Gini index was used to identify the strongest predictors of preclinical AD. RESULTS: The F1 score of the RF models for identifying preclinical AD was 0.85 using APOE ε4 status and age only, 0.82 using GPS-based driving indicators only, 0.88 using age and driving indicators, and 0.91 using age, APOE ε4 status, and driving. The area under the receiver operating curve for the final model was 0.96. CONCLUSION: The findings suggest that GPS driving may serve as an effective and accurate digital biomarker for identifying preclinical AD among older adults

The Butcher-Oemler Effect at Moderate Redshift

We present the results of Butcher-Oemler-style analysis of three moderate- redshift (0.1<z<0.2) clusters which have bimodal X-ray surface brightness profiles. We find that at least two of these clusters exhibit unusually high fractions of blue galaxies as compared to clusters at comparable redshifts studied by Butcher and Oemler (1984). This implies that star formation is occurring in a high fraction of the galaxies in the two clusters. Our results are consistent with hierarchical clustering models in which subcluster- subcluster mergers create shocks in the intracluster medium. The shocks, in turn, induce simultaneous starbursts in a large fraction of cluster galaxies. Our study therefore lends weight to the hypothesis that the Butcher-Oemler effect is an environmental, as well as evolutionary, phenomenon.Comment: 22 pages, 8 figures; accepted for publication in A

Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL. METHODS: 419 participants (Clinical Dementia Rating [CDR] Scale \u3e 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL. RESULTS: CSF NfL increased with age (r = 0.59, p \u3c 0.001). Elevated CSF NfL was associated with greater total WMH volume (p \u3c 0.001), but not gray or white matter volume (p\u27s \u3e 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R CONCLUSIONS: CSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease