Vitamin D status and biomarkers of functional health and ageing in very-old adults : analysis of the Newcastle 85+ study

PhD ThesisThe number of those aged over 80 years-old (the “very-old”) will increase from 5% of the population in European countries in 2010, to more than 10% of the population by 2050 (OECD, 2013). Very little is known about the nutritional intake, nutritional status and its association with health and wellbeing in the very-old. Due to its diverse biological effects, vitamin D has gained immense interest recently as a potential modifier for a range of health outcomes This PhD systematically reviewed the available literature to provide an accurate snapshot of vitamin D status in the very-old. It also used a unique dataset from the Newcastle 85+ Study, a longitudinal community-dwelling study of health trajectory and outcomes conducted in over 800 people from the North-East of England aged 85 years. The overall aim of using this data were to explore vitamin D association with a range of functional and ageing biomarkers in the very-old. Vitamin D status [25(OH)D] was available for 775 participants, and measured by immunoassays at baseline only and divided to the following concentration: 50 nmol/l (high). Disability was measured using a questionnaire on the difficulty of performing 17 Activities of Daily Living at baseline, 1.5, 3 and 5 years. NTproBNP was measured using an electrochemiluminescent sandwich immunoassay. The HbA1c was measured using a Tosoh Eurogenetics automated HLC-723G7 HPLC analyser. Telomere Length was measured as an abundance of telomeric template vs. a single gene by quantitative real-time PCR. Spirometry and peak flow measurements were to obtain three technically satisfactory maximal effort ‘blows’ to generate reproducible FEV1and FVC. Results of the systematic review showed that prevalence of deficiency varies by latitude and living conditions of the participants, and that vitamin D deficiency is widespread in many regions, particularly in Europe. Using the Newcastle 85+ Study data also showed a high prevalence of vitamin D deficiency (>30%) was found amongst very-old adults. Findings of this thesis indicate that participants with low 25(OH)D concentration (<25 nmol/l) were more likely to have a poorer disability trajectory over 5 years compared with those with moderate concentration (25–50 nmol/l) (OR= 3.12, 95% CI= 1.6–5.8, p= 0.001), although physical activity was the strongest predictor of disability trajectories. However, this thesis could not prove the protective effect of vitamin D in regards to metabolic and cardiopulmonary health biomarkers (NT-proBNP, HbA1c, FEV1, FVC and diastolic blood pressure) in fully adjusted models at baseline or over 18 and 36 months. Finally, high 25(OH)D concentration is positively associated with Telomere Length (95%CI= 12.0-110.3, B= 61.2+25.0, p=0.015) but does not have protective effects over 18 and 36 months. In conclusion, this thesis highlights that vitamin D deficiency is very common in very-old adults and that low vitamin D status is associated with at least some functional and ageing biomarkers in this under studied age group.Saudi Arabian Government and to Umm Al Qura Universit

The Relationship Between Audit Services and Non-Audit Actuarial Services in the Auditor’s Report

Purpose: In view of the trend toward using international financial reporting standards when generating financial statements, we looked at the interaction between audit services and non-audit services for auditors in the context of actuarial services for insurance firms. CPAs are authorized to work in banks and insurance businesses, but those with a practicing license obtained after earning a higher academic degree are not. Design/methodology/approach: A small number of auditing firms control the decisions issued by the Iraqi Accountants Association, monopolizing audit services in banks and insurance businesses. In the case of actuarial services used in reserve estimation, they are credited to an external party's account without any verification of the Reliability of the reserve estimation procedure. Originality/value: In addition to audit services, a scale has been developed to examine the auditors' non-audit actuarial services. The financial reporting rules for insurance contracts 17 and the examinations for acquiring an actuarial certificate in the United States of America are used to create this scale. Findings: The findings show that there is no substantial relationship between the two services supplied, and we recommend that the actuarial services be audited by specialist international companies that support the auditors' judgment on the computation of expected reserves in the financial accounts. Conducting specialist courses in the actuarial profession, and obtaining this credential is a requirement for auditing insurance companies

The newcastle 85+ study

Funding Information: Funding: The Newcastle 85+ study was jointly funded by the Medical Research Council and Biotechnology and Biomedical Science Research Council (G0500997), now part of UK Research and Innovation (UKRI) in addition to the Newcastle Healthcare Charity. The following waves were funded by the Dunhill Medical Trust (R124/0509), Newcastle University, UK Medical Research Council and the British Heart Foundation. Overall, the project was supported by National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. This particular analysis (vitamin D and telomere length) received no additional external funding. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from crosssectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as 50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0–110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = −59.9–−7.5, B = −33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.publishersversionpublishe

Impact of Moringa oleifera Leaf and Flaxseed on Lipid Oxidation and Microbiological Characteristics of Chicken Burger During Cold Storage

Background: Practice of making burgers out of chicken instead of red meat is gaining popularity. because of their high fat substance and on account of no social or strict limitations to the utilization of poultry. The present study aimed to assess effect of adding Moringa oleifera leaf and flaxseed combinations on lipid oxidation and microbiological traits of chicken burger during cold storage.Methods: In this study the pH, peroxide value, thiobarbituric acid (TBA) as well as microbiological characteristics of chicken burger formulated by various levels of Moringa oleifera leaf and flaxseed powder were evaluated. Samples were as follows: control=0%FS+0%MLP; T1=20%FS+0%MLP; T2=15%FS+5%MLP; T3=10%FS+10%MLP; T4=5%FS+15%MLP; andT5=0%FS+20%MLP.Results: The results showed that the pH value of burger samples supplemented with Moringa oleifera and flaxseed was decreased (P≤0.05) with an increasing period of storage and ranged between 3.5–5.1 and 3.3-4.9 when stored for 15 and 30 days, respectively.Conclusion: Peroxide values of T2, T3, T4 and T5 as well as the value of TBA within the MLP-treated and FS-treated samples (P 0.05) decreased with the progression of the storage period. Microbiological characteristics (P 0.05) were affected by the incorporation of MLP and FS in chicken burger treatments.Keywords: Burger; T.B.A.; Peroxide value; Contamination; Coliform bacteria;  E.coli; Moringa oleifera; Flaxseed   

The newcastle 85+ study

Background: Low vitamin D status is common in very old adults which may have adverse consequences for muscle function, a major predictor of disability. Aims: To explore the association between 25-hydroxyvitamin D [25(OH)D] concentrations and disability trajectories in very old adults and to determine whether there is an ‘adequate’ 25(OH)D concentration which might protect against a faster disability trajectory. Methodology: A total of 775 participants from the Newcastle 85+ Study for who 25(OH)D concentration at baseline was available. Serum 25(OH)D concentrations of 50 nmol/L were used as cut-offs to define low, moderate and high vitamin D status, respectively. Disability was defined as difficulty in performing 17 activities of daily living, at baseline, after 18, 36 and 60 months. Results: A three-trajectory model was derived (low-to-mild, mild-to-moderate and moderate-to-severe). In partially adjusted models, participants with 25(OH)D concentrations <25 nmol/L were more likely to have moderate and severe disability trajectories, even after adjusting for sex, living in an institution, season, cognitive status, BMI and vitamin D supplement use. However, this association disappeared after further adjustment for physical activity. Conclusions: Vitamin D status does not appear to influence the trajectories of disability in very old adults.publishersversionpublishe

Exploring the Variable Sky with LINEAR. III. Classification of Periodic Light Curves

We describe the construction of a highly reliable sample of ~7000 optically faint periodic variable stars with light curves obtained by the asteroid survey LINEAR across 10,000 deg^2 of the northern sky. The majority of these variables have not been cataloged yet. The sample flux limit is several magnitudes fainter than most other wide-angle surveys; the photometric errors range from ~0.03 mag at r = 15 to ~0.20 mag at r = 18. Light curves include on average 250 data points, collected over about a decade. Using Sloan Digital Sky Survey (SDSS) based photometric recalibration of the LINEAR data for about 25 million objects, we selected ~200,000 most probable candidate variables with r < 17 and visually confirmed and classified ~7000 periodic variables using phased light curves. The reliability and uniformity of visual classification across eight human classifiers was calibrated and tested using a catalog of variable stars from the SDSS Stripe 82 region and verified using an unsupervised machine learning approach. The resulting sample of periodic LINEAR variables is dominated by 3900 RR Lyrae stars and 2700 eclipsing binary stars of all subtypes and includes small fractions of relatively rare populations such as asymptotic giant branch stars and SX Phoenicis stars. We discuss the distribution of these mostly uncataloged variables in various diagrams constructed with optical-to-infrared SDSS, Two Micron All Sky Survey, and Wide-field Infrared Survey Explorer photometry, and with LINEAR light-curve features. We find that the combination of light-curve features and colors enables classification schemes much more powerful than when colors or light curves are each used separately. An interesting side result is a robust and precise quantitative description of a strong correlation between the light-curve period and color/spectral type for close and contact eclipsing binary stars (β Lyrae and W UMa): as the color-based spectral type varies from K4 to F5, the median period increases from 5.9 hr to 8.8 hr. These large samples of robustly classified variable stars will enable detailed statistical studies of the Galactic structure and physics of binary and other stars and we make these samples publicly available

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707