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Abstract Gamma‐hydroxy‐butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß‐amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high‐resolution atlas‐based 1H‐magnetic resonance spectroscopic imaging (MRSI) at ultra‐high magnetic field strength of 7 Tesla for gray matter‐specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß‐burden (ß = 0.60, p

Abstract INTRODUCTION Female sex is associated with increased [18F]‐flortaucipir signal, which may be affected by amyloid pathology, age, and off‐target binding in skull and meninges. METHODS In this cross‐sectional study comprising 52 females and 52 matched males, we examined sex‐related differences in regional tau‐positron emission tomography (PET) with and without considering off‐target binding. We assessed the respective contributions of sex, age, amyloid‐PET burden, and off‐target binding to tau‐PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau‐PET signals. RESULTS Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid‐independent associations were largely reduced when controlling for off‐target binding. Age but not age*sex interactions explained a small but significant amount of tau‐PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid‐PET burden, no clear associations between regional tau‐PET signals and age at menopause or HRT use could be found. DISCUSSION Female sex is associated with increased [18F]‐flortaucipir signal mainly through its interaction with amyloid.

The use of tungsten fiber-reinforced tungsten composites (Wf/W) has been demonstrated to significantly enhance the mechanical properties of tungsten (W) by incorporating W-fibers into the W-matrix. However, prior research has been restricted by the usage of single fiber-based textile fabrics, consisting of 150 µm warp and 50 µm weft filaments, with limited homogeneity, reproducibility, and mechanical properties in bulk structures due to the rigidity of the 150 µm W-fibers. To overcome this limitation, two novel textile preforms were developed utilizing radial braided W-yarns with 7 core and 16 sleeve filaments (R.B. 16 + 7), with a diameter of 25 µm each, as the warp material. In this study, bulk composites of two different fabric types were produced via a layer-by-layer CVD process, utilizing single 50 µm filaments (type 1) and R.B. 16 + 7 yarns (type 2) as weft materials. The produced composites were sectioned into KLST-type specimens based on DIN EN ISO 179-1:2000 using electrical discharge machining (EDM) and subjected to three-point bending tests. Both composites demonstrated enhanced mechanical properties with pseudo-ductile behavior at room temperature and withstood over 10,000 load cycles between 50–90% of their respective maximum load without sample fracture in three-point cyclic loading tests. Furthermore, a novel approach to predict the fatigue behavior of the material under cyclic loading was developed based on the high reproducibility of the composites produced, especially for the composite based on type 1. This approach provides a new benchmark for upscaling endeavors and may enable a better prediction of the service life of the produced components made of Wf/W in the future. In comparison, the composite based on fabric type 1 demonstrated superior results in manufacturing performance and mechanical properties. With a high relative average density (>97%), a high fiber volume fraction (14–17%), and a very homogeneous fiber distribution in the CVD-W matrix, type 1 shows a promising option to be further tested in high heat flux tests and to be potentially used as an alternative to currently used materials for the most stressed components of nuclear fusion reactors or other potential application fields such as concentrated solar power (CSP), aircraft turbines, the steel industry, quantum computing, or welding tools. Type 2 composites have a higher layer spacing compared to type 1, resulting in gaps within the matrix and less homogeneous material properties. While type 2 composites have demonstrated a notable enhancement over 150 µm fiber-based composites, they are not viable for industrial scale-up unlike type 1 composites.

Tungsten-fibre-reinforced tungsten composites (Wf/W) have been in development to overcome the inherent brittleness of tungsten as one of the most promising candidates for the first wall and divertor armour material in a future fusion power plant. As the development of Wf/W continues, the fracture toughness of the composite is one of the main design drivers. In this contribution, the efforts on size upscaling of Wf/W based on Chemical Vapour Deposition (CVD) are shown together with fracture mechanical tests of two different size samples of Wf/W produced by CVD. Three-point bending tests according to American Society for Testing and Materials (ASTM) Norm E399 for brittle materials were used to obtain a first estimation of the toughness. A provisional fracture toughness value of up to 346MPam1/2 was calculated for the as-fabricated material. As the material does not show a brittle fracture in the as-fabricated state, the J-Integral approach based on the ASTM E1820 was additionally applied. A maximum value of the J-integral of 41kJ/m2 (134.8MPam1/2) was determined for the largest samples. Post mortem investigations were employed to detail the active mechanisms and crack propagation.

Abstract Musculoskeletal disorders (MSDs) are highly prevalent, burdensome, and putatively associated with an altered human resting muscle tone (HRMT). Osteopathic manipulative treatment (OMT) is commonly and effectively applied to treat MSDs and reputedly influences the HRMT. Arguably, OMT may modulate alterations in HRMT underlying MSDs. However, there is sparse evidence even for the effect of OMT on HRMT in healthy subjects. A 3 × 3 factorial randomised trial was performed to investigate the effect of myofascial release (MRT), muscle energy (MET), and soft tissue techniques (STT) on the HRMT of the corrugator supercilii (CS), superficial masseter (SM), and upper trapezius muscles (UT) in healthy subjects in Hamburg, Germany. Participants were randomised into three groups (1:1:1 allocation ratio) receiving treatment, according to different muscle-technique pairings, over the course of three sessions with one-week washout periods. We assessed the effect of osteopathic techniques on muscle tone (F), biomechanical (S, D), and viscoelastic properties (R, C) from baseline to follow-up (primary objective) and tested if specific muscle-technique pairs modulate the effect pre- to post-intervention (secondary objective) using the MyotonPRO (at rest). Ancillary, we investigate if these putative effects may differ between the sexes. Data were analysed using descriptive (mean, standard deviation, and quantiles) and inductive statistics (Bayesian ANOVA). 59 healthy participants were randomised into three groups and two subjects dropped out from one group (n = 20; n = 20; n = 19–2). The CS produced frequent measurement errors and was excluded from analysis. OMT significantly changed F (−0.163 [0.060]; p = 0.008), S (−3.060 [1.563]; p = 0.048), R (0.594 [0.141]; p 0.05). Subgroup analysis revealed a significant sex-specific difference for F from baseline to follow-up. No adverse events were reported. OMT modified the HRMT in healthy subjects which may inform future research on MSDs. In detail, MRT, MET, and STT reduced the muscle tone (F), decreased biomechanical (S not D), and increased viscoelastic properties (R and C) of the SM and UT (CS was not measurable). However, the effect on HRMT was not modulated by muscle–technique interaction and showed sex-specific differences only for F. Trial registration German Clinical Trial Register (DRKS00020393).

BackgroundThe ATN model represents a research framework used to describe in subjects the presence or absence of Alzheimer’s disease (AD) pathology through biomarkers. The aim of this study was to describe the prevalence of different ATN profiles using quantitative imaging biomarkers in two independent cohorts, and to evaluate the pertinence of ATN biomarkers to identify comparable populations across independent cohorts.MethodsA total of 172 subjects from the Geneva Memory Clinic and 113 volunteers from a study on healthy aging at the University Hospital of Zurich underwent amyloid (A) and tau (T) PET, as well as T1-weigthed MRI scans using site-specific protocols. Subjects were classified by cognition (cognitively unimpaired, CU, or impaired, CI) based on clinical assessment by experts. Amyloid data converted into the standardized centiloid scale, tau PET data normalized to cerebellar uptake, and hippocampal volume expressed as a ratio over total intracranial volume ratio were considered as biomarkers for A, T, and neurodegeneration (N), respectively. Positivity for each biomarker was defined based on previously published thresholds. Subjects were then classified according to the ATN model. Differences among profiles were tested using Kruskal-Wallis ANOVA, and between cohorts using Wilcoxon tests.ResultsTwenty-nine percent of subjects from the Geneva cohorts were classified with a normal (A−T−N−) profile, while the Zurich cohort included 64% of subjects in the same category. Meanwhile, 63% of the Geneva and 16% of the Zurich cohort were classified within the AD continuum (being A+ regardless of other biomarkers’ statuses). Within cohorts, ATN profiles were significantly different for age and mini-mental state examination scores, but not for years of education. Age was not significantly different between cohorts. In general, imaging A and T biomarkers were significantly different between cohorts, but they were no longer significantly different when stratifying the cohorts by ATN profile. N was not significantly different between cohorts.ConclusionStratifying subjects into ATN profiles provides comparable groups of subjects even when individual recruitment followed different criteria.

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INTRODUCTION: We investigated the interactive associations between amyloid and hypertension on the entorhinal cortex (EC) tau and atrophy and the role of cerebral blood flow (CBF) as a shared mechanism by which amyloid and hypertension contribute to EC tau and regional white matter hyperintensities (WMHs). METHODS: We analyzed data from older adults without dementia participating in the Add‐Tau study (NCT02958670, n = 138) or Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 523) who had available amyloid‐positron emission tomography (PET), tau‐PET, fluid‐attenuated inversion recovery (FLAIR), and T1‐weighted magnetic resonance imaging (MRI). A subsample in both cohorts had available arterial spin labeling (ASL) MRI (Add‐Tau: n = 78; ADNI: n = 89). RESULTS: The detrimental effects of hypertension on AD pathology and EC thickness were more pronounced in the Add‐Tau cohort. Increased amyloid burden was associated with decreased occipital gray matter CBF in the ADNI cohort. In both cohorts, lower regional gray matter CBF was associated with higher EC tau and posterior WMH burden. DISCUSSION: Reduced cerebral perfusion may be one common mechanism through which hypertension and amyloid are related to increased EC tau and WMH volume. Highlights: Hypertension is associated with increased entorhinal cortex (EC) tau, particularly in the presence of amyloid.Decreased cortical cerebral blood flow (CBF) is associated with higher regional white matter hyperintensity volume.Increasing amyloid burden is associated with decreasing CBF in the occipital lobe.MTL CBF and amyloid are synergistically associated with EC tau. [ABSTRACT FROM AUTHOR]

Abstract Background At the beginning of the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), little was known about its actual rate of infectivity and any COVID-19 patient positive in laboratory testing was supposed to be highly infective and a public health risk factor. Methods One hundred oropharyngeal samples were obtained during routine work flow of testing symptomatic persons by quantitative polymerase chain reaction (qPCR) and were inoculated onto cell culture of VeroB4 cells to study the degree of infectivity of SARS-CoV-2 in vitro. Quantification by virus titration and an external standard using synthetic RNA gave the breaking point of infectivity in SARS-CoV-2 in vitro. Results A clear negative correlation (r = − 0.76; p