Electronic structure of fully epitaxial Co2TiSn thin films

In this article we report on the properties of thin films of the full Heusler compound Co2TiSn prepared by DC magnetron co-sputtering. Fully epitaxial, stoichiometric films were obtained by deposition on MgO (001) substrates at substrate temperatures above 600{\deg}C. The films are well ordered in the L21 structure, and the Curie temperature exceeds slightly the bulk value. They show a significant, isotropic magnetoresistance and the resistivity becomes strongly anomalous in the paramagnetic state. The films are weakly ferrimagnetic, with nearly 1 \mu_B on the Co atoms, and a small antiparallel Ti moment, in agreement with theoretical expectations. From comparison of x-ray absorption spectra on the Co L3/L2 edges, including circular and linear magnetic dichroism, with ab initio calculations of the x-ray absorption and circular dichroism spectra we infer that the electronic structure of Co2TiSn has essentially non-localized character. Spectral features that have not been explained in detail before, are explained here in terms of the final state band structure.Comment: 11 pages, 8 figure

Correction: Performance of risk prediction scores for cardiovascular mortality in older persons: External validation of the SCORE OP and appraisal

[This corrects the article DOI: 10.1371/journal.pone.0231097.

Self-reported medication in community-dwelling older adults in Germany: results from the Berlin Initiative Study

Background: Older adults have the highest drug utilization due to multimorbidity. Although the number of people over age 70 is expected to double within the next decades, population-based data on their medication patterns are scarce especially in combination with polypharmacy and potentially inappropriate medication (PIM). Our objective was to analyse the frequency of polypharmacy, pattern of prescription (PD) and over-the-counter (OTC) drug usage, and PIMs according to age and gender in a population-based cohort of very old adults in Germany. Methods: Cross-sectional baseline data of the Berlin Initiative Study, a prospective cohort study of community-dwelling adults aged ≥70 years with a standardized interview including demographics, lifestyle variables, co-morbidities, and medication assessment were analysed. Medication data were coded using the Anatomical Therapeutic Chemical (ATC) classification. Age- and sex-standardized descriptive analysis of polypharmacy (≥5 drugs, PD and OTC vs. PD only and regular and on demand drugs vs regular only), medication frequency and distribution, including PIMs, was performed by age (</≥80) and gender. Results: Of 2069 participants with an average age of 79.5 years, 97% (95%CI [96%;98%]) took at least one drug and on average 6.2 drugs (SD = 3.5) with about 40 to 66% fulfilling the criteria of polypharmacy depending on the definition. Regarding drug type more female participants took a combination of PD and OTC (male: 68%, 95%CI [65%;72%]); female: 78%, 95%CI [76%;80%]). Most frequently used were drugs for cardiovascular diseases (85%, 95%CI [83%;86%]). Medication frequency increased among participants aged ≥80 years, especially for cardiovascular drugs, antithrombotics, psychoanaleptics and dietary supplements. Among the top ten prescription drugs were mainly cardiovascular drugs including lipid-lowering agents (simvastatin), beta-blockers (metoprolol, bisoprolol) and ACE inhibitors (ramipril). The most common OTC drug was acetylsalicylic acid (35%; 95%CI [33%;37%])). Dose-independent PIM were identified for 15% of the participants. Conclusions: Polypharmacy was excessive in older adults, with not only PD but also OTC drugs contributing to the high point prevalence. The medication patterns reflected the treatment of chronic diseases in this age group. There was even an increase in medication frequency between below and above 80 years especially for drugs of cardiovascular diseases, antithrombotic medication, psychoanaleptics, and dietary supplements

Is there an association between social determinants and care dependency risk? A multi‐state model analysis of a longitudinal study

Despite a growing body of knowledge about the morbidities and functional impairment that frequently lead to care dependency, the role of social determinants is not yet well understood. The purpose of this study was to examine the effect of social determinants on care dependency onset and progression. We used data from the Berlin Initiative Study, a prospective, population-based cohort study including 2,069 older participants living in Berlin. Care dependency was defined as requiring substantial assistance in at least two activities of daily living for 90 min daily (level 1) or 3+ hours daily (level 2). Multi-state time to event regression modeling was used to estimate the effects of social determinants (partnership status, education, income, and sex), morbidities, and health behaviors, characteristics, and conditions. During the study period, 556 participants (27.5%) changed their status of care dependency. Participants without a partner at baseline were at a higher risk to become care-dependent than participants with a partner (hazard ratio [HR], 95% confidence interval [CI]: 1.24 (1.02-1.51)). After adjustment for other social determinants, morbidities and health behaviors, characteristics, and conditions the risk decreased to a HR of 1.19 (95% CI: 0.79-1.79). Results indicate that older people without a partner may tend to be at higher risk of care dependency onset but not at higher risk of care dependency progression. Clinicians should inquire about and consider patients' partnership status as they evaluate care needs

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/− nab-paclitaxel in elderly pancreatic cancer patients (GrantPax)

Background: In the group of elderly patients (≥70 years) with metastatic pancreatic ductal adenocarcinoma (mPDAC), it is not known who benefits from intensive 1st line nab-paclitaxel/gemcitabine (nab-p/gem) combination chemotherapy or who would rather suffer from increased toxicity. We aim to determine whether treatment individualization by comprehensive geriatric assessments (CGAs) improves functional outcome of the patients. Methods/Design: GrantPax is a multicenter, open label phase 4 interventional trial. We use a CGA to stratify elderly patients into three parallel treatment groups (n = 45 per arm): 1) GOGO (nab-p/gem), 2) SLOWGO (gem mono) or 3) FRAIL (best supportive care). After the 1st cycle of chemotherapy (or 4 weeks in FRAIL group) another CGA and safety assessment is performed. CGA-stratified patients may not decline in their CGA performance in response to the first cycle of chemotherapy (primary objective), measured as a loss of 5 points or less in Barthels activities of daily living. Based on the second CGA, patients are re-assigned to their definite treatment arm and undergo further CGAs to monitor the course of treatment. Secondary endpoints include CGA scores during the course of therapy (CGA1–4), response rates, safety and survival rates. Discussion: GrantPax is the first trial implementing a CGA-driven treatment to personalize therapy for elderly patients with pancreatic cancer. This may lead to standardization of therapy decisions for elderly patients and may optimize standard of care for this increasing group of patients. Trial registration: NCT02812992 , registered 24.06.2016

Creative beyond TikToks : investigating adolescents' social privacy management on TikTok

TikTok has been criticized for its low privacy standards, but little is known about how its adolescent users protect their privacy. Based on interviews with 54 adolescents in Switzerland, this study provides a comprehensive understanding of young TikTok users' privacy management practices related to the creation of videos. The data were explored using the COM-B model, an established behavioral analysis framework adapted for sociotechnical privacy research. Our overall findings are in line with previous research on other social networks: adolescents are aware of privacy related to their online social connections (social privacy) and perform conscious privacy management. However, we also identified new patterns related to the central role of algorithmic recommendations potentially relevant for other social networks. Adolescents are aware that TikTok's special algorithm, combined with the app's high prevalence among their peers, could easily put them in the spotlight. Some adolescents also reduce TikTok, which was originally conceived as a social network, to its extensive audio-visual capabilities and share TikToks via more private channels (e.g., Snapchat) to manage audiences and avoid identification by peers. Young users also find other creative ways to protect their privacy such as identifying stalkers or maintaining multiple user accounts with different privacy settings to establish granular audience management. Based on our findings, we propose various concrete measures to develop interventions that protect the privacy of adolescents on TikTok

Hypoxia-induced downregulation of microRNA-186-5p in endothelial cells promotes non-small cell lung cancer angiogenesis by upregulating protein kinase C alpha

The tumor microenvironment stimulates the angiogenic activity of endothelial cells (ECs) to facilitate tumor vascularization, growth, and metastasis. The involvement of microRNA-186-5p (miR-186) in regulating the aberrant activity of tumor-associated ECs has so far not been clarified. In the present study, we demonstrated that miR-186 is significantly downregulated in ECs microdissected from human non-small cell lung cancer (NSCLC) tissues compared with matched non-malignant lung tissues. In vitro analyses of primary human dermal microvascular ECs (HDMECs) exposed to different stimuli indicated that this miR-186 downregulation is triggered by hypoxia via activation of hypoxia-inducible factor 1 alpha (HIF1a). Transfection of HDMECs with miR-186 mimic (miR-186m) significantly inhibited their proliferation, migration, tube formation, and spheroid sprouting. In contrast, miR-186 inhibitor (miR-186i) exerted pro-angiogenic effects. In vivo, endothelial miR-186 overexpression inhibited the vascularization of Matrigel plugs and the initial growth of tumors composed of NSCLC cells (NCI-H460) and HDMECs. Mechanistic analyses revealed that the gene encoding for protein kinase C alpha (PKCa) is a bona fide target of miR-186. Activation of this kinase significantly reversed the miR-186mrepressed angiogenic activity of HDMECs. These findings indicate that downregulation of miR-186 in ECs mediates hypoxia-stimulated NSCLC angiogenesis by upregulating PKCa

Suppression of endothelial miR-22 mediates non-small cell lung cancer cell-induced angiogenesis

MicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22 is preferentially and highly expressed in ECs, while its endothelial level is significantly downregulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched nontumor lung tissues. This reduction of endothelial miR-22 is possibly induced by NSCLC cell-secreted interleukin-1b and subsequently activated transcription factor nuclear factor-kB. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all of the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin 1 and fibroblast growth factor receptor 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin signaling. These findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future antiangiogenic treatment of NSCLC