Severe mental illness and chronic kidney disease: a cross-sectional study in the United Kingdom

OBJECTIVE: We investigated the burden of chronic kidney disease (CKD) among patients with severe mental illness (SMI). METHODS: We identified patients with SMI among all those aged 25–74 registered in the UK Clinical Practice Research Datalink as on March 31, 2014. We compared the prevalence of CKD (two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and renal replacement therapy between patients with and without SMI. For patients with and without a history of lithium prescription separately, we used logistic regression to examine the association between SMI and CKD, adjusting for demographics, lifestyle characteristics, and known CKD risk factors. RESULTS: The CKD prevalence was 14.6% among patients with SMI and a history of lithium prescription (n = 4,295), 3.3% among patients with SMI and no history of lithium prescription (n = 24,101), and 2.1% among patients without SMI (n = 2,387,988; P < 0.001). The prevalence of renal replacement therapy was 0.23%, 0.15%, and 0.11%, respectively (P = 0.012). Compared to patients without SMI, the fully adjusted odds ratio for CKD was 6.49 (95% CI 5.84–7.21) for patients with SMI and a history of lithium prescription and 1.45 (95% CI 1.34–1.58) for patients with SMI and no history of lithium prescription. The higher prevalence of CKD in patients with SMI may, in part, be explained by more frequent blood testing as compared to the general population. CONCLUSION: CKD is identified more commonly among patients with SMI than in the general population

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Introduction Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Methods Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Results Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. Discussion Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI

Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults

BACKGROUND: Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer's disease (AD) pathology and neurodegeneration. OBJECTIVE: This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration. METHODS: Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n = 152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-β42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognitive (NC), mild cognitive impairment (MCI)). RESULTS: Higher LVEF related to decreased CSF Aβ42 levels (β= -6.50, p = 0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p = 0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p = 0.004) and p-tau levels (p = 0.002), whereas lower LVEF was associated with increased CSF t-tau (β= -9.74, p = 0.01) and p-tau in the NC (β= -1.41, p = 0.003) but not MCI participants (p-values>0.13). CONCLUSIONS: Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life

Giant Magnetostriction in Annealed Co\u3csub\u3e1-x\u3c/sub\u3eFe\u3csub\u3ex\u3c/sub\u3e Thin-Films

Chemical and structural heterogeneity and the resulting interaction of coexisting phases can lead to extraordinary behaviours in oxides, as observed in piezoelectric materials at morphotropic phase boundaries and relaxor ferroelectrics. However, such phenomena are rare in metallic alloys. Here we show that, by tuning the presence of structural heterogeneity in textured Co1−xFex thin films, effective magnetostriction λeff as large as 260 p.p.m. can be achieved at low-saturation field of ~10 mT. Assuming λ100 is the dominant component, this number translates to an upper limit of magnetostriction ofλ100≈5λeff \u3e1,000 p.p.m. Microstructural analyses of Co1−xFex films indicate that maximal magnetostriction occurs at compositions near the (fcc+bcc)/bcc phase boundary and originates from precipitation of an equilibrium Co-rich fcc phase embedded in a Fe-rich bcc matrix. The results indicate that the recently proposed heterogeneous magnetostriction mechanism can be used to guide exploration of compounds with unusual magnetoelastic properties

The impacts avoided with a 1.5 °C climate target: a global and regional assessment

The 2015 Paris Agreement commits countries to pursue efforts to limit the increase in global mean temperature to 1.5 °C above pre-industrial levels. We assess the consequences of achieving this target in 2100 for the impacts that are avoided, using several indicators of impact (exposure to drought, river flooding, heat waves and demands for heating and cooling energy). The proportion of impacts that are avoided is not simply equal to the proportional reduction in temperature. At the global scale, the median proportion of projected impacts avoided by the 1.5 °C target relative to a rise of 4 °C ranges between 62 and 95% across sectors: the greatest reduction is for heat wave impacts. The 1.5 °C target results in impacts that would be between 27 and 62% lower than with the 2 °C target. For each indicator, there are differences in the proportions of impacts avoided between regions depending on exposure and the regional changes in climate (particularly precipitation). Uncertainty in the proportion of impacts that are avoided for a specific sector depends on the range in the shape of the relationship between global temperature change and impact, and this varies between sectors

Adverse Vascular Risk Relates to Cerebrospinal Fluid Biomarker Evidence of Axonal Injury in the Presence of Alzheimer's Disease Pathology

BACKGROUND: Vascular risk factors promote cerebral small vessel disease and neuropathological changes, particularly in white matter where large-caliber axons are located. How Alzheimer's disease pathology influences the brain's vulnerability in this regard is not well understood. OBJECTIVE: Systemic vascular risk was assessed in relation to cerebrospinal fluid concentrations of neurofilament light, a biomarker of large-caliber axonal injury, evaluating for interactions by clinical and protein markers of Alzheimer's disease. METHODS: Among Alzheimer's Disease Neuroimaging Initiative participants with normal cognition (n = 117), mild cognitive impairment (n = 190), and Alzheimer's disease (n = 95), linear regression related vascular risk (as measured by the modified Framingham Stroke Risk Profile) to neurofilament light, adjusting for age, sex, education, and cognitive diagnosis. Interactions were assessed by cognitive diagnosis, and by cerebrospinal fluid markers of Aβ42, hyperphosphorylated tau, and total tau. RESULTS: Vascular risk and neurofilament light were not related in the main effect model (p = 0.08). However, interactions emerged for total tau (p = 0.01) and hyperphosphorylated tau (p = 0.002) reflecting vascular risk becoming more associated with cerebrospinal fluid neurofilament light in the context of greater concentrations of tau biomarkers. An interaction also emerged for the Alzheimer's disease biomarker profiles (p = 0.046) where in comparison to the referent 'normal' biomarker group, individuals with abnormal levels of both Aβ_{42} and total tau showed stronger associations between vascular risk and neurofilament light. CONCLUSION: Older adults may be more vulnerable to axonal injury in response to higher vascular risk burdens in the context of concomitant Alzheimer's disease pathology

Mentoring programs for medical students - a review of the PubMed literature 2000 - 2008

Abstract Background Although mentoring is acknowledged as a key to successful and satisfying careers in medicine, formal mentoring programs for medical students are lacking in most countries. Within the framework of planning a mentoring program for medical students at Zurich University, an investigation was carried out into what types of programs exist, what the objectives pursued by such programs are, and what effects are reported. Methods A PubMed literature search was conducted for 2000 - 2008 using the following keywords or their combinations: mentoring, mentoring program, medical student, mentor, mentee, protégé, mentorship. Although a total of 438 publications were identified, only 25 papers met the selection criteria for structured programs and student mentoring surveys. Results The mentoring programs reported in 14 papers aim to provide career counseling, develop professionalism, increase students' interest in research, and support them in their personal growth. There are both one-to-one and group mentorships, established in the first two years of medical school and continuing through graduation. The personal student-faculty relationship is important in that it helps students to feel that they are benefiting from individual advice and encourages them to give more thought to their career choices. Other benefits are an increase in research productivity and improved medical school performance in general. Mentored students also rate their overall well-being as higher. - The 11 surveys address the requirements for being an effective mentor as well as a successful mentee. A mentor should empower and encourage the mentee, be a role model, build a professional network, and assist in the mentee's personal development. A mentee should set agendas, follow through, accept criticism, and be able to assess performance and the benefits derived from the mentoring relationship. Conclusion Mentoring is obviously an important career advancement tool for medical students. In Europe, more mentoring programs should be developed, but would need to be rigorously assessed based on evidence of their value in terms of both their impact on the career paths of juniors and their benefit for the mentors. Medical schools could then be monitored with respect to the provision of mentorships as a quality characteristic.</p

Cerebrospinal fluid β-amyloid₄₂ and neurofilament light relate to white matter hyperintensities

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid₄₂ deposition (Aβ₄₂), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ₄₂ (β = −0.001, p = 0.007) and NFL (β = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ₄₂ accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury