Vitamin D and immunity

Vitamin D deficiency has been linked to an increased risk of a wide range of adverse health outcomes. The active form of vitamin D has an important role in calcium metabolism and in bone mineralisation, but the evidence for other health outcomes is mixed, with the strongest effects seen in the weakest epidemiological study designs. There are plausible pathways whereby vitamin D deficiency can impair immune function, resulting in both overactivity and increased risk of autoimmune disease, as well as immune suppression with poorer resistance to infection. Vitamin D status may influence the bacterial flora that constitute the microbiome and affect immune function through this route. Exposure of the skin to ultraviolet radiation causes the production of a range of chemicals, including vitamin D, and new research is exploring possible vitamin D-independent immunomodulatory pathways

A novel approach for prediction of vitamin D status using support vector regression

BACKGROUND Epidemiological evidence suggests that vitamin D deficiency is linked to various chronic diseases. However direct measurement of serum 25-hydroxyvitamin D (25(OH)D) concentration, the accepted biomarker of vitamin D status, may not be feasible in large epidemiological studies. An alternative approach is to estimate vitamin D status using a predictive model based on parameters derived from questionnaire data. In previous studies, models developed using Multiple Linear Regression (MLR) have explained a limited proportion of the variance and predicted values have correlated only modestly with measured values. Here, a new modelling approach, nonlinear radial basis function support vector regression (RBF SVR), was used in prediction of serum 25(OH)D concentration. Predicted scores were compared with those from a MLR model. METHODS Determinants of serum 25(OH)D in Caucasian adults (n = 494) that had been previously identified were modelled using MLR and RBF SVR to develop a 25(OH)D prediction score and then validated in an independent dataset. The correlation between actual and predicted serum 25(OH)D concentrations was analysed with a Pearson correlation coefficient. RESULTS Better correlation was observed between predicted scores and measured 25(OH)D concentrations using the RBF SVR model in comparison with MLR (Pearson correlation coefficient: 0.74 for RBF SVR; 0.51 for MLR). The RBF SVR model was more accurately able to identify individuals with lower 25(OH)D levels (<75 nmol/L). CONCLUSION Using identical determinants, the RBF SVR model provided improved prediction of serum 25(OH)D concentrations and vitamin D deficiency compared with a MLR model, in this dataset.Dr. Guo is funded by an Australian Postgraduate Award. Prof. Lucas is funded by a National Health and Medical Research (NHMRC) Career Development Fellowship and receives research funding from Cancer Australia, NHMRC, and MS Research Australia. Prof. Ponsonby is funded by a NHMRC Research Fellowship and receives research funding from NHMRC and MS Research Australia. The Ausimmune Study was funded by the US National Multiple Sclerosis Society, NHMRC, and MS Research Australia

Oregon Psychologists on Prescriptive Authority: Divided Views and Little Knowledge

With over half of all states having considered legislating prescriptive authority, an immense amount of time and money has been invested. The literature is limited in terms of understanding if opinions toward prescriptive authority are grounded in knowledge and what implications that has for altering these opinions. Following a veto of a prescriptive authority bill in Oregon, 399 licensed Oregon clinical psychologists were surveyed regarding their attitudes and knowledge. In terms of knowledge, only 6.5% knew which three states/territories currently have prescriptive authority and 70.4% were unfamiliar with any of the prerequisites for postdoctoral training in psychopharmacology. Reflecting division, 43.4% were in favor, 25.4% were undecided, and 31.2% were in opposition to broadening privileges for psychologists. Further, only 15.2% expressed interest in pursuing training or 6.7% in becoming prescribers. Data on access, training, and legislative costs were presented to participants in the education condition. These participants showed significant gains in their knowledge across all domains and their opinions shifted only in these specific areas leaving their general stance on the issue unchanged. In contrast to ardent supporters who argue that their “data should provide reassurance to psychologists spearheading legislative initiatives” because of high approval ratings (Sammons et al., 2000, p. 608), our data suggest disagreement amongst a group of professionals who are not particularly well-informed, nor interested in becoming prescribers. Future work should investigate whether expanding the data relevant to other facets of the argument contributes to further targeted change or an overall change in opinion toward prescriptive authority

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

BACKGROUND Reactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample. RESULTS EBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 10² to 1.3 × 10⁸ copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 10³ to 2.0 × 10⁵ copies/ml in infectious mononucleosis (n = 7), 7.5 × 10⁴ to 1.1 × 10⁵ copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 10² to 5.6 × 10³ copies/ml in HIV-infected patients (n = 12), and 2.0 × 10² to 9.1 × 10⁴ copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11). CONCLUSION Two sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.The Ausimmune Study is funded by the National Multiple Sclerosis Society of the USA, the National Health & Medical Research Council (Project Grant 316901) and Multiple Sclerosis Research Australia

Searches for Supersymmetry with compressed mass spectra using monojet events with the CMS detector at the LHC

A novel search for supersymmetric particles in events with one high transverse momentum jet and large missing transverse energy is performed using an integrated luminosity of 19.7/fb of pp collision data collected using the CMS detector at the Large Hadron Collider. By using events with an energetic radiated jet, sensitivity to supersymmetric models with compressed mass spectra is gained where the decay products have very low energy. Standard Model background estimates are evaluated with the use of data control samples. No excess over Standard Model expectations is observed, and limits are placed on third generation squark production at the 95% confidence level using supersymmetric simplified models. The development of a Level 1 trigger algorithm to reconstruct jets in the Phase 1 Upgrade of the CMS detector is presented. Utilising the full granularity of the CMS calorimeter and time-multiplexed-trigger technology, a new algorithm with increased flexibility and resolution is presented. It is possible to measure and subtract the contribution to calorimeter deposits of soft particles originating from multiple pp vertices in an event, on an event-by-event basis, in order to decrease the trigger rates associated with high luminosity future run conditions. This will enable CMS to maintain, or better, its ability to do physics as centre-of-mass energy and instantaneous luminosity of the LHC increases in the years to come.Open Acces

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D Supplementation (SEDS) Study

BACKGROUND Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. METHODS/DESIGN The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. DISCUSSION This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013