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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.
Grazing experiments have shown that using a ryegrass (Lolium perenne L.) variety bred by conventional techniques for high water-soluble carbohydrate (WSC) concentrations can improve liveweight gain in pre-weaned lambs (Lee et al., 2001) and increase milk yields and reduce N excretion in dairy cows (Miller et al., 2001) compared to conventional ryegrass. The aim of this study was to determine the effects of using reseeded upland pastures, sown with either a ryegrass variety bred for elevated levels of WSC or a control ryegrass on the production performance of grazing steers when compared to steers grazing permanent ryegrass/white clover pastures.
Livestock farming is a traditional and important contributor to the rural economy in the hills and uplands of the UK. However, significant areas of the uplands have seen a decline in the condition of heath and mire habitats and the loss of dwarf shrubs as a result of over-grazing. Attempts to halt the decline and improve the condition of upland heath and mire habitats have been undertaken by the introduction of agri-environment schemes. In the main, such schemes rely on the reduction of sheep numbers. However, recent Defra funded research (LS1508) has indicated that this can result in dominance by competitive and/or unpalatable species such as purple moor-grass (Molinia caerulea ) or mat-grass (Nardus stricta ), leading in time to a reduction in the physical and financial performance of the flock. The objective of this study is to assess the impact of cattle grazing on Nardus stricta dominated pasture on sheep and cattle performance. It is being carried out as part of a wider project to determine environmentally sustainable and economically viable grazing systems for heather moorland.
The efficiency of grass nitrogen utilisation for milk production tends to be low, due partly to the slow rate of release of energy in the rumen which reduces the efficiency of capture of rapidly degradable plant proteins by the rumen microbial population. When additional sugars are infused into the rumen, microbial protein production is increased (Rooke et al., 1987). The objective of this study was to assess milk production using a grass variety that has been bred to express elevated water soluble carbohydrate (WSC) concentrations.
Eight multiparous Holstein-Friesian dairy cows in mid lactation (176 days ± s.e. 3.6) were used in a continuous design, zero-grazing experiment. Following covariate measurements taken from all animals on a standard grazing diet, four animals were each offered one of two varieties of perennial ryegrass at ad libitum rate: AberDove, bred to express high WSC concentrations; and AberElan, a commercially available variety, used as a control.
The efficiency of utilisation of grass nitrogen for milk protein production tends to be low, because rumen fermentable energy sources limit the amount of diet amino acids that are incorporated into microbial protein. As a consequence, absorption of ammonia from the rumen and excretion of high-N waste products is considerable. Previous studies (Miller et al., 1999) have shown that the efficiency of use of feed N can be increased in late-lactation dairy cows by feeding ryegrass bred to contain a high concentration of water soluble carbohydrates (WSC). The objective of this study was to investigate milk production and N partitioning in early lactation dairy cows using the same high WSC ryegrass variety, AberDove.
Sheep group breeding schemes have gained in popularity in recent years. The objectives of group breeding schemes are to improve desirable traits such as carcass conformation, weight and maternal ability whilst maintaining local type. However, if group breeding schemes were to work together then a larger genetic pool of performance recorded animals would be available to facilitate improvements. The objectives of this project were therefore twofold, 1.) was to improve traits such as weight and carcass conformation and 2.) to demonstrate the benefits of cooperative groups working together. In this project, group breeding schemes from North and Mid Wales have been working together with ram performance testing groups from North, South and Mid Wales to improve results from Welsh Mountain breeding schemes.
The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation.
A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services.
Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives.
Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs.
Escherichia coli O157 are zoonotic bacteria for which cattle are an important reservoir. Prevalence estimates for E. coli O157 in British cattle for human consumption are over 10 years old. A new baseline is needed to inform current human health risk. The British E. coli O157 in Cattle Study (BECS) ran between September 2014 and November 2015 on 270 farms across Scotland and England & Wales. This is the first study to be conducted contemporaneously across Great Britain, thus enabling comparison between Scotland and England & Wales. Herd-level prevalence estimates for E. coli O157 did not differ significantly for Scotland (0·236, 95% CI 0·166–0·325) and England & Wales (0·213, 95% CI 0·156–0·283) (P = 0·65). The majority of isolates were verocytotoxin positive. A higher proportion of samples from Scotland were in the super-shedder category, though there was no difference between the surveys in the likelihood of a positive farm having at least one super-shedder sample. E. coli O157 continues to be common in British beef cattle, reaffirming public health policy that contact with cattle and their environments is a potential infection source.
We have found that 4 new, bright IRAS quasars, out of 7 observed, have strong, non-variable, wavelength-dependent polarization. Three show degrees of polarization, pλ, increasing from infrared to UV wavelengths (Fig. 1), which implies a combination of a polarized, scattered spectrum and a much redder, unpolarized spectrum. Detailed IR and optical polarimetry and spectrophotometry of one, IRAS 13349+2438 (Wills et al.), shows a polarized flux spectrum, pλxFλ, (continuum and Pa α, Hα, and Hβ broad hydrogen lines) typical of unreddened, luminous quasars. This suggests that the path of scattered light from a central, luminous quasar is low in dust and that the polarization of the scattered spectrum is wavelength independent. The latter is most easily explained by electron scattering although the data do not exclude dust scattering. When this polarized flux spectrum is subtracted from the total spectrum, we are left with a very reddened line and continuum spectrum, E(B-V) = 0.3 to 0.7, which we attribute to the same luminous quasar seen through a thick dusty torus. The angle of polarization is parallel to the major axis of the r-band image, presumed to be that of the host galaxy. If the torus is in the plane of the galaxy, the axial ratio suggests a viewing angle of 40° to the plane of the torus. Fig. 2 illustrates the geometry. The appearance of the quasar at optical and UV wavelengths will depend strongly on viewing angle, suggesting that present samples of quasars selected by colours, optical flux density, or quasi-stellar appearance, may be seriously biased, with important consequences for studies of the space density and evolution of AGN.
The error box of the unusual Gamma-Ray Burst of March 5, 1979 falls completely inside the optical and radio image of the Supernova Remnant N49 in the Large Magellanic Cloud. This region was observed twice in x-rays with the High Resolution Imager of the Einstein Observatory, six weeks and nearly two years after the Gamma-Ray Burst. We show the comparison between the two observations.
Atom probe tomography and transmission electron microscopy are used to analyze magnetron-sputtered MoS2 films containing Ti and Au/Sb2O3 as a model system for tribological coatings. Transmission electron microscopy characterization showed that the Ti–MoS2 film is dense and featureless whereas Sb2O3/Au–MoS2 film is less dense and have columnar morphology. Three-dimensional atom probe reconstructions revealed that the Ti–MoS2 films have a homogeneous composition and contain about 15 at.% Ti, which is uniformly distributed throughout the MoS2 matrix without any evidence of Ti precipitation. Sb2O3/Au–MoS2 films also showed homogeneous distribution of Sb2O3 throughout the MoS2 matrix and the presence of Au-rich precipitates. The complementary techniques of atom probe tomography and transmission electron microscopy indicate that Ti and Sb2O3 incorporation in the deposition of MoS2 produces amorphous microstructures, whereas the addition of Au forms nano-sized and well-dispersed precipitates.
Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results.
Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol.
Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size).
Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.
Research supports robust associations between childhood bullying victimization and mental health problems in childhood/adolescence and emerging evidence shows that the impact can persist into adulthood. We examined the impact of bullying victimization on mental health service use from childhood to midlife.
We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort Study. We conducted analyses on 9242 participants with complete data on childhood bullying victimization and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimization and mental health service use at the ages of 16, 23, 33, 42 and 50 years. We estimated incidence and persistence of mental health service use over time to the age of 50 years.
Compared with participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.88–3.40] and also in midlife (OR 1.30, 95% CI 1.10–1.55). Disparity in service use associated with childhood bullying victimization was accounted for by both incident service use through to age 33 years by a subgroup of participants, and by persistent use up to midlife.
Childhood bullying victimization adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs.
The Harwell system for measuring milligram size samples using Brookhaven miniature gas counters is fully operative. It comprises 12 counters of different sizes which operate simultaneously within a single NaI crystal (300mm diameter × 300mm long) acting as an anti-coincidence guard counter. Brief details are given of the construction and commissioning of the system, including counter assembly, shield design, electronics, data capture, data analysis, and chemical processing and filling procedures. The performance of the system and an overall view of the fields of application for which the counters have important applications are discussed.
Background: Epileptic encephalopathy (EE) is a severe condition in which epileptic activity itself may contribute to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone. Next generation sequencing technologies such as whole exome sequencing (WES) can detect underlying genetic causes of in EE. Methods: This report describes genotype-phenotype correlation of 29 subjects with unexplained epileptic encephalopathy, in whom WES, targeting a list of 557 epilepsy-associated genes was performed. Epilepsy phenotyping was done according to current ILAE recommendations. Results: Median age at seizure onset was 14 months (range 1-48). Electroclinical syndromes were applicable for 16/29, 8/16 had a definite/likely diagnosis. 6/8 subjects with West syndrome had variants in ALG13, STXBP1, PAFAH1B1, SLC35A2, CDKL5 and ADSL. 2 patients with Dravet syndrome had variants in SCN1A and PCDH19 respectively. 4/29 had unspecified EE and definite/likely diagnosis due to STXBP1, POLG, and KCNQ2 (2) variants. 4/29 had a possible diagnosis involving GABRB3, ARHGEF9, PCDH19 and SCN3A variants. Conclusions: The high diagnostic yield (definite/likely diagnosis in 11/29 = 38%), involving a broad variety of epilepsy-associated genes in different electroclinical syndromes justifies the diagnostic approach of early onset EE by next generation sequencing.
We use a new, robust, method to estimate the identification probabilities of optical matches from digitized plate catalogs (COSMOS/UKST Catalog of the Southern Sky Version 2, Yentis et al. 1992; The Guide Star Catalog Version 1.1, Lasker et al. 1990; The Tycho Input Catalog, Egret et al. 1992; The APM Northern Sky Catalogue, Irwin, Maddox and McMahon 1994) to sources in the IRAS Faint Source Survey (FSS; Moshir et al. 1992), including both the Catalog (FSC) and the Reject File (FSR), utilizing a new random matching procedure with the advantages that it: (1) eliminates systematic uncertainties due to many problems, such as uncertainty in N(m); variations across the optical plate of magnitudes, plate limits or N(m); misclassification of stars and galaxies; the assumption of Gaussian error ellipses, etc. and (2) properly calibrates the identification probabilities. We find that at high SNRs and high galactic latitudes essentially all IR star-colored sources have an optical identification with Pid > 99%. At high SNRs and high galactic latitudes, ∼ 90% of all IR galaxy-colored sources have an optical identification with Pid > 90%.
The volume of work published on extragalactic astronomy in the period August 1966 – July 1969 has been large. Limitations of space have precluded the writing of an all-inclusive report; in all sections some selection has had to be made. References are given, whenever possible, by the reference numbers of the Bulletin Signalétique of the CNRS of France, with the omission of the Section number: “2” for vols. 27 to 29 and “120” for vol. 30. A reference number preceded by J is taken from the Astronomischer Jahresbericht. When no reference numbers were available, abbreviated journal references have been given.