Plasticity of topologically close-packed phases in the Fe-Ta(-Al) system

Understanding the structure-property relationships of materials plays a significant role in the development of materials for technical applications. Due to the many possible combinations of two or more elements, intermetallic phases can be very interesting for these developments. High strength up to high temperatures makes intermetallics promising materials for high-temperature applications. However, their complex structure, resulting in a pronounced brittleness, has so far limited their applicability. We focus on the understanding of plastic deformation in topologically close-packed (TCP) phases, which form one of the largest groups of intermetallics. To do this, we use nanomechanical tests that allow us to study plasticity even in the most brittle materials. Here, we consider the Fe-Ta(-Al) system that contains two closely related TCP phases, a C14 Laves phase and a µ-phase. The building block-like structure of these phases enables a systematic investigation as well as a transfer of the findings to other complex crystals. The mechanical properties of the two TCP phases in the Fe-Ta(-Al) system, investigated by state-of-the-art micromechanical testing, are introduced in this work. The influence of the crystal structure and chemical composition on the mechanical properties and the deformation mechanisms of the TCP phases are discussed

Chemical and structural characterization of the native oxide scale on a Mg-based alloy

In this study, the structure and composition of the native oxide forming on the basal plane (0001) of Mg-2Al-0.1Ca is investigated by a correlative approach, combining scanning transmission electron microscopy (STEM) and atom probe tomography (APT). Atom probe specimens were prepared conventionally in a Ga focused ion beam (FIB) as well as a Xe plasma FIB in a cryogenic setup and subsequently cleaned in the atom probe to remove surface contamination before oxidation. While thermal energy input from the laser and longer atmospheric exposure time increased the measured hydrogen content in the specimen's apex region, cryo preparation revealed, that the hydrogen uptake in magnesium is independent of the employment of conventional or cryogenic FIB preparation. TEM measurements demonstrated the growth of a (111) MgO oxide layer with 3-4 nm thickness on the basal (0001) plane of the Mg atom probe specimen. APT data further revealed the formation of an aluminum-rich region between bulk Mg and the native oxide. The aluminum enrichment of up to ~20 at.% at the interface is consistent with an inward growth of the oxide scale

Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation

BackgroundAtrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI.Materials and methodsWe used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW).ResultsThe mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW (n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison (n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (−0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used.ConclusionIn this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT02105844]

Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND Atrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI. MATERIALS AND METHODS We used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW). RESULTS The mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW (n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison (n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (-0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used. CONCLUSION In this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function. CLINICAL TRIAL REGISTRATION [https://clinicaltrials.gov/], identifier [NCT02105844]

Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC)

Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates

Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA; 2; DS; 2; -VASc score (congestive heart failure, hypertension, age 65-74 or >75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72 years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA; 2; DS; 2; -VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA; 2; DS; 2; -VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10 years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100 cm; 3; smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort

Objective: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories. Methods: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications. Results: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs. Conclusion: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs. Keywords: Atrial Fibrillation; Health Care Economics and Organization