The elastic constants of MgSiO3 perovskite at pressures and temperatures of the Earth's mantle

The temperature anomalies in the Earth's mantle associated with thermal convection1 can be inferred from seismic tomography, provided that the elastic properties of mantle minerals are known as a function of temperature at mantle pressures. At present, however, such information is difficult to obtain directly through laboratory experiments. We have therefore taken advantage of recent advances in computer technology, and have performed finite-temperature ab initio molecular dynamics simulations of the elastic properties of MgSiO3 perovskite, the major mineral of the lower mantle, at relevant thermodynamic conditions. When combined with the results from tomographic images of the mantle, our results indicate that the lower mantle is either significantly anelastic or compositionally heterogeneous on large scales. We found the temperature contrast between the coldest and hottest regions of the mantle, at a given depth, to be about 800K at 1000 km, 1500K at 2000 km, and possibly over 2000K at the core-mantle boundary.Comment: Published in: Nature 411, 934-937 (2001

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

Survival benefits of statins for primary prevention: a cohort study

Objectives: Estimate the effect of statin prescription on mortality in the population of England and Wales with no previous history of cardiovascular disease.  Methods: Primary care records from The Health Improvement Network 1987-2011 were used.Four cohorts of participants aged 60, 65, 70, or 75 years at baseline included 118,700,199,574, 247,149, and 194,085 participants; and 1.4, 1.9, 1.8, and 1.1 million person-years of data, respectively. The exposure was any statin prescription at any time before the participant reached the baseline age (60, 65, 70 or 75) and the outcome was all-cause mortality at any age above the baseline age. The hazard of mortality associated with statin prescription was calculated by Cox's proportional hazard regressions, adjusted for sex, year of birth, socioeconomic status, diabetes,antihypertensive medication, hypercholesterolaemia, body mass index, smoking status, and general practice. Participants were grouped by QRISK2 baseline risk of afirst cardiovascular event in the next ten years of <10%, 10-19%, or ≥20%.  Results: There was no reduction in all-cause mortality for statin prescription initiated in participants with a QRISK2 score <10% at any baseline age, or in participants aged 60at baseline in any risk group. Mortality was lower in participants with a QRISK2 score≥20% if statin prescription had been initiated by age 65 (adjusted hazard ratio (HR)0.86 (0.79-0.94)), 70 (HR 0.83 (0.79-0.88)), or 75 (HR 0.82 (0.79-0.86)). Mortality reduction was uncertain with a QRISK2 score of 10-19%: the HR was 1.00 (0.91-1.11)for statin prescription by age 65, 0.89 (0.81-0.99) by age 70, or 0.79 (0.52-1.19) by age75.  Conclusions: The current internationally recommended thresholds for statin therapy for primary prevention of cardiovascular disease in routine practice may be too low and may lead to overtreatment of younger people and those at low risk

Gender differences in the associations between age trends of social media interaction and well-being among 10-15 year olds in the UK

Background Adolescents are among the highest consumers of social media while research has shown that their well-being decreases with age. The temporal relationship between social media interaction and well-being is not well established. The aim of this study was to examine whether the changes in social media interaction and two well-being measures are related across ages using parallel growth models. Methods Data come from five waves of the youth questionnaire, 10-15 years, of the Understanding Society, the UK Household Longitudinal Study (pooled n =9859). Social media interaction was assessed through daily frequency of chatting on social websites. Well-being was measured by happiness with six domains of life and the Strengths and Difficulties Questionnaire. Results Findings suggest gender differences in the relationship between interacting on social media and well-being. There were significant correlations between interacting on social media and well-being intercepts and between social media interaction and well-being slopes among females. Additionally higher social media interaction at age 10 was associated with declines in well-being thereafter for females, but not for males. Results were similar for both measures of well-being. Conclusions High levels of social media interaction in early adolescence have implications for well-being in later adolescence, particularly for females. The lack of an association among males suggests other factors might be associated with their reduction in well-being with age. These findings contribute to the debate on causality and may inform future policy and interventions

Detection of delirium by nurses among long-term care residents with dementia

<p>Abstract</p> <p>Background</p> <p>Delirium is a prevalent problem in long-term care (LTC) facilities where advanced age and cognitive impairment represent two important risk factors for this condition. Delirium is associated with numerous negative outcomes including increased morbidity and mortality. Despite its clinical importance, delirium often goes unrecognized by nurses. Although rates of nurse-detected delirium have been studied among hospitalized older patients, this issue has been largely neglected among demented older residents in LTC settings. The goals of this study were to determine detection rates of delirium and delirium symptoms by nurses among elderly residents with dementia and to identify factors associated with undetected cases of delirium.</p> <p>Methods</p> <p>In this prospective study (N = 156), nurse ratings of delirium were compared to researcher ratings of delirium. This procedure was repeated for 6 delirium symptoms. Sensitivity, specificity, positive and negative predictive values were computed. Logistic regressions were conducted to identify factors associated with delirium that is undetected by nurses.</p> <p>Results</p> <p>Despite a high prevalence of delirium in this cohort (71.5%), nurses were able to detect the delirium in only a minority of cases (13%). Of the 134 residents not identified by nurses as having delirium, only 29.9% of them were correctly classified. Detection rates for the 6 delirium symptoms varied between 39.1% and 58.1%, indicating an overall under-recognition of symptoms of delirium. Only the age of the residents (≥ 85 yrs) was associated with undetected delirium (OR: 4.1; 90% CI: [1.5–11.0]).</p> <p>Conclusion</p> <p>Detection of delirium is a major issue for nurses that clearly needs to be addressed. Strategies to improve recognition of delirium could result in a reduction of adverse outcomes for this very vulnerable population.</p

Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms