1,084 research outputs found

    Sublithospheric diamond ages and the supercontinent cycle.

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    Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700‚ÄČkm depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Ju√≠na (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300‚ÄČMyr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability

    The multilayered effects of initial teacher education programs on the beginning teacher workforce and workplace: Perceptions of beginning teachers and their school leaders

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    Initial teacher education (ITE) impacts the preparedness of beginning teachers. A large scale mixed methods investigation (n‚ÄĮ=‚ÄĮ2145) offers perceptions through surveys of beginning teachers in their first five years of teaching (n‚ÄĮ=‚ÄĮ1362) and their school leaders (n‚ÄĮ=‚ÄĮ736) and one-on-one semi-structured interviews (n‚ÄĮ=‚ÄĮ47) with beginning teachers (n‚ÄĮ=‚ÄĮ38) and school leaders (n‚ÄĮ=‚ÄĮ9). The findings offer a deeper understanding of ITEs influence on beginning teachers‚Äô preparedness. Qualitative analysis of survey open questions and the quantitative analysis of beginning teachers (n‚ÄĮ=‚ÄĮ504) and school leaders‚Äô (n‚ÄĮ=‚ÄĮ306) completed Likert scale surveys items unveiled perceptions about ITEs impact on beginning teachers‚Äô satisfaction levels, expectations and realities; professional support and mentoring offered at school level; and professional interrelationships within schools

    Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

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    Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ¬Ī 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH

    Redox phospholipidomics discovers pro-ferroptotic death signals in A375 melanoma cells in vitro and in vivo

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    Growing cancer cells effectively evade most programs of regulated cell death, particularly apoptosis. This necessitates a search for alternative therapeutic modalities to cause cancer cell's demise, among them ‚Äď ferroptosis. One of the obstacles to using pro-ferroptotic agents to treat cancer is the lack of adequate biomarkers of ferroptosis. Ferroptosis is accompanied by peroxidation of polyunsaturated species of phosphatidylethanolamine (PE) to hydroperoxy- (-OOH) derivatives, which act as death signals. We demonstrate that RSL3-induced death of A375 melanoma cells in vitro was fully preventable by ferrostatin-1, suggesting their high susceptibility to ferroptosis. Treatment of A375¬†cells with RSL3 caused a significant accumulation of PE-(18:0/20:4-OOH) and PE-(18:0/22:4-OOH), the biomarkers of ferroptosis, as well as oxidatively truncated products - PE-(18:0/hydroxy-8-oxo-oct-6-enoic acid (HOOA) and PC-(18:0/HOOA). A significant suppressive effect of RSL3 on melanoma growth was observed in vivo (utilizing a xenograft model of inoculation of GFP-labeled A375¬†cells into immune-deficient athymic nude mice). Redox phospholipidomics revealed elevated levels of 18:0/20:4-OOH in RSL3-treated group vs controls. In addition, PE-(18:0/20:4-OOH) species were identified as major contributors to the separation of control and RSL3-treated groups, with the highest variable importance in projection predictive score. Pearson correlation analysis revealed an association between tumor weight and contents of PE-(18:0/20:4-OOH) (r¬†=¬†‚ąí0.505), PE-18:0/HOOA (r¬†=¬†‚ąí0.547) and PE 16:0-HOOA (r¬†=¬†‚ąí0.503). Thus, LC-MS/MS based redox lipidomics is a sensitive and precise approach for the detection and characterization of phospholipid biomarkers of ferroptosis induced in cancer cells by radio- and chemotherapy

    Efficacy and Safety Profiles of Antipsychotic Drugs as Viewed by Psychiatrists: A Comparative Analysis of Cariprazine and Risperidone

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    BACKGROUND: Physicians hold the belief that the treatment outcomes and the treatment strategy they eventually adopt is largely determined by the differences in medications. Despite numerous studies focusing on the decision-making processes of psychiatrists, including the choice of antipsychotics when prescribing pharmacotherapy, the impact of therapeutic drug profiling on physicians‚Äô decision-making remains poorly comprehended. AIM: The aim of this study is to assess the quantitative differences in perceptions of antipsychotics by psychiatrists using cariprazine and risperidone as examples. METHODS: A total of 79 psychiatrists were interviewed anonymously in St. Petersburg, Russia. The physicians documented the clinical advantages they perceived drugs to possess relative to one another, following a predetermined principle: A B, A=B, A B (2-AC protocol). The comparison is based on eleven parameters that assess the effectiveness and safety of cariprazine or risperidone. It has been hypothesized that the pattern of responses (qualitative difference) and the degree of preference for each drug (quantitative difference) may not align with the data in the original meta-analyses. RESULTS: The perception parameter exhibited a greater difference than anticipated (őī ‚ÄĒ 0.889), while the threshold for differentiating between the drugs was lower (ŌĄ ‚ÄĒ 1.001). The response pattern only aligned with theory by 44.37%. The dispersion of responses was associated with the length of work experience. CONCLUSION: The perceived difference between the drugs significantly deviates from the theoretical data, both in terms of strength of perception and pattern (quantitative and qualitative differences)

    Diminishing benefits of urban living for children and adolescents’ growth and development

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    Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1‚Äď6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5‚Äď19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m‚Äď2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

    Refining and optimising a behavioural intervention to support endocrine therapy adherence (ROSETA) in UK women with breast cancer : protocol for a pilot fractional factorial trial

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    Introduction Women with breast cancer who do not adhere to adjuvant endocrine therapy (AET) have increased risks of mortality and recurrence. There are multiple barriers to AET adherence, including medication side-effects, beliefs about medication, memory and psychological distress. We developed four intervention components, each targeting a different barrier. This pilot trial is part of the preparation phase of the Multiphase Optimisation Strategy, and aims to establish key trial parameters, establish intervention component adherence, establish availability and feasibility of outcome and process data, estimate variability in planned outcome measures and estimate cost of developing and delivering each intervention component. Methods and analysis The four intervention components are as follows: short message service text reminders (target: memory); a written information leaflet (target: medication beliefs); a guided self-help Acceptance and Commitment Therapy programme (target: psychological flexibility to reduce distress) and a self-management website (target: side-effect management). To evaluate the feasibility of recruitment, acceptability of the intervention components and the availability of outcome data, we will conduct a multisite, exploratory pilot trial using a 2 4-1 fractional factorial design, with a nested process evaluation. We will randomise 80 women with early-stage breast cancer who have been prescribed AET to one of eight experimental conditions. This will determine the combination of intervention components they receive, ranging from zero to four, with all conditions receiving usual care. Key outcomes of interest include medication adherence and quality of life. Progression to the optimisation phase will be based on predefined criteria for consent rates, patient adherence to intervention components and availability of medication adherence data. Ethics and dissemination The study was reviewed by the Wales Research Authority Research Ethics Committee 3 (21/WA/0322). Written informed consent will be obtained from all patients before randomisation. The results of this trial will be disseminated in a peer-reviewed journal. Trial registration number ISRTCN10487576

    Acceptability, fidelity and trial experience of four intervention components to support medication adherence in women with breast cancer: A process evaluation protocol for a pilot fractional factorial trial [version 2; peer review: 2 approved]

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    Background: The Refining and Optimising a behavioural intervention to Support Endocrine Therapy Adherence (ROSETA) programme has developed four intervention components aiming to improve medication adherence in women with early-stage breast cancer. These are (a) text messages, (b) information leaflet, (c) Acceptance and Commitment Therapy-based guided self-help (ACT), (d) side-effect management website. Guided by the Multiphase Optimisation Strategy, our pilot trial will use a fractional factorial design to evaluate the feasibility of undertaking a larger optimisation trial. The pilot will include a process evaluation to maximise learning regarding the fidelity and acceptability of the intervention components before proceeding with a larger trial. The trial process evaluation has three aims: to assess the (1) fidelity and (2) acceptability of the intervention components; and (3) to understand participant’s trial experience, and barriers and facilitators to recruitment and retention. Methods: The process evaluation will use multiple methods. Fidelity of the intervention components will be assessed using self-reported questionnaire data, trial data on intervention component adherence, and observations of the ACT sessions. Acceptability of the intervention components and trial experience will be explored using an acceptability questionnaire and interviews with patients and trial therapists. Trial experience will be assessed using a questionnaire and interviews with participants, while barriers and facilitators to recruitment and retention will be assessed using a questionnaire completed by research nurses and participant interviews. The pilot trial opened for recruitment on 20th May 2022 and was open at the time of submission. Conclusions: This process evaluation will provide information regarding whether the intervention components can be delivered with fidelity within a national healthcare setting and are acceptable to participants. We will also better understand participant experience in a pilot trial with a fractional factorial design, and any barriers and facilitators to recruitment and retention. Registration: ISRCTN registry (ISRCTN10487576, 16/12/2021)
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