Stimulated PBMC-produced IFN-γ and TNF-α are associated with altered relapse risk in multiple sclerosis: results from a prospective cohort study.

BACKGROUND: Altered reactivity of peripheral blood mononuclear cells (PBMC) and their production of cytokines may affect multiple sclerosis (MS) clinical course. We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS. METHODS: Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis. RESULTS: Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk. CONCLUSIONS: We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.

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.

Think UV, not heat!

BACKGROUND: Australia has the highest incidence of skin cancer in the world, a preventable disease caused primarily by exposure to ultraviolet radiation (UVR) in sunlight. Health promotion strategies play a significant role in sun protection. OBJECTIVES: To assess the understanding of a population sample as to the time of year that the sun was 'at its most burning' in Melbourne, Australia. METHODS: A cross-sectional study was performed using questionnaires completed at corporate skin checks, conducted on 668 participants during 2011 to 2013. RESULTS: Only a minority (n = 82, 12%) gave the correct theoretical answer; the summer solstice or 21-22 December, while another 38% (n = 254) correctly named December and January as the times when the UVR is actually highest. In all, 18% (n = 122) said February was the month when the temperature is hottest and 170 (25%) either mentioned the period May-August when UVR is negligible in Melbourne or had no idea, including saying 'all year round'. There was no significant difference in this knowledge between different age groups. CONCLUSION: One-quarter of participants did not understand that sunburn was related to high levels of UVR, which occur in summer. Almost one-fifth associated the heat of February with the highest UVR. Understanding these concepts is important for Australians residing in cooler parts of southern Australia, as UVR levels may be high and yet the temperature may be relatively cool. There needs to be more emphasis on UVR in sun awareness campaigns to prompt sun-protective behaviour.

Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis.

OBJECTIVE: A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied. We investigated whether higher levels of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of relapses in people with MS. METHODS: We conducted a prospective cohort study of 145 participants with relapsing-remitting MS from 2002 to 2005. Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis. RESULTS: There was an inverse linear relationship between 25-OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% confidence interval [CI]: 0.85-0.97) per 10 nmol/l increase in 25-OH-D level (p = 0.006). When variation due to timing of blood collection was removed by estimating 25-OH-D at the start of each season, this association persisted, with HR 0.90 (95% CI, 0.83-0.98) per 10 nmol/l increase (p = 0.016). Taking into account the biological half-life of 25-OH-D, we estimated 25-OH-D at monthly intervals, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82-0.95) per 10 nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings. INTERPRETATION: In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10 nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.

Validity of covering-up sun-protection habits: Association of observations and self-report.

BACKGROUND: Few studies have reported the accuracy of measures used to assess sun-protection practices. Valid measures are critical to the internal validity and use of skin cancer control research. OBJECTIVES: We sought to validate self-reported covering-up practices of pool-goers. METHODS: A total of 162 lifeguards and 201 parent/child pairs from 16 pools in 4 metropolitan regions in the United States completed a survey and a 4-day sun-habits diary. Observations of sun-protective behaviors were conducted on two occasions. RESULTS: Agreement between observations and diaries ranged from slight to substantial, with most values in the fair to moderate range. Highest agreement was observed for parent hat use (kappa = 0.58-0.70). There was no systematic pattern of over- or under-reporting among the 3 study groups. LIMITATIONS: Potential reactivity and a relatively affluent sample are limitations. CONCLUSION: There was little over-reporting and no systematic bias, which increases confidence in reliance on verbal reports of these behaviors in surveys and intervention research.

Estimation of avoidable skin cancers and cost-savings to government associated with regulation of the solarium industry in Australia.

OBJECTIVE: In Australia there is growing concern about the expanding solarium industry, and the additive effect of persons seeking exposure to artificial ultraviolet radiation (UVR) against already intense background levels of solar UVR. We estimated the numbers of potential skin cancers prevented through regulation of solaria and the associated cost-savings to the Federal Government. METHODS: A lifetime decision-analytic model was created using relative risk estimates based on a meta-analysis of the literature assessing the link between skin cancer risk and solarium use. The costs were limited to those incurred by Medicare Australia, for the medical care of individuals treated for skin cancer. RESULTS: With stricter regulations, we estimated between 18 and 31 melanomas, 200-251 squamous cell carcinomas and associated costs of $AU 256,054 would be avoided per 100,000 persons. Our base findings were sensitive to estimates for prevalence of use, skin cancer risk and discounting rates. CONCLUSIONS: Continued growth in the Australian solarium industry is likely to inflate the already substantial skin cancer burden. Subject to some limitations, our study indicates that by successfully enforcing solarium regulations to prohibit use by minors and by those with fair skin colour, the Federal Government could expect favourable cost and health benefits.

Measured occupational solar UVR exposures of lifeguards in pool settings.

BACKGROUND: The aim of this study was to measure ultraviolet radiation (UVR) exposures of lifeguards in pool settings and evaluate their personal UVR protective practices. METHODS: Lifeguards (n = 168) wore UVR sensitive polysulfone (PS) film badges in wrist bracelets on 2 days and completed a survey and diary covering sun protection use. Analyses were used to describe sun exposure and sun protection practices, to compare UVR exposure across locations, and to compare findings with recommended threshold limits for occupational exposure. RESULTS: The measured UVR exposures varied with location, ranging from high median UVR exposures of 6.2 standard erythemal doses (SEDs) to the lowest median of 1.7 SEDs. More than 74% of the lifeguards' PS badges showed UVR above recommended threshold limits for occupational exposure. Thirty-nine percent received more than four times the limit and 65% of cases were sufficient to induce sunburn. The most common protective behaviors were wearing sunglasses and using sunscreen, but sun protection was often inadequate. CONCLUSIONS: At-risk individuals were exposed to high levels of UVR in excess of occupational limits and though appropriate types of sun protection were used, it was not used consistently and more than 50% of lifeguards reported being sunburnt at least twice during the previous year.

Season, Terrestrial Ultraviolet Radiation, and Markers of Glucose Metabolism in Children Living in Perth, Western Australia.

Seasonality in glucose metabolism has been observed in adult populations; however, little is known of the associations between season and glucose metabolism in children. In this study, we examined whether markers of glucose metabolism (fasting glucose, insulin and HbA1c) varied by season in a paediatric population (6-13 years of age) located in Perth (Western Australia, n = 262) with data categorised by weight. Linear regression was used to analyse the nature of the relationships between mean daily levels of terrestrial ultraviolet radiation (UVR) (prior to the day of the blood test) and measures of glucose metabolism. Fasting blood glucose was significantly lower in autumn compared to spring, for children in combined, normal and obese weight categories. Fasting insulin was significantly lower in autumn and summer compared to winter for individuals of normal weight. HbA1c was significantly higher in summer (compared with winter and spring) in overweight children, which was in the opposite direction to other published findings in adults. In children with obesity, a strong inverse relationship (r = -0.67, p = 0.002) was observed for fasting glucose, and daily terrestrial UVR levels measured in the previous 6 months. Increased safe sun exposure in winter therefore represents a plausible means of reducing fasting blood sugar in children with obesity. However, further studies, using larger paediatric cohorts are required to confirm these relationships.

A pilot study of the validity of self-reported ultraviolet radiation exposure and sun protection practices among lifeguards, parents and children.

Outdoor recreation settings, such as swimming pools, provide a promising venue to assess UVR exposure and sun protection practices among individuals who are minimally clothed and exposed to potentially high levels of UVR. Most studies assessing sun exposure/protection practices rely on self-reported data, which are subject to bias. The aim of this study was to establish the feasibility of conducting a multimethod study to examine the validity of self-reported measures within a swimming pool setting. Data were collected from 27 lifeguards, children and parents in Hawaii. Each participant filled out a survey and a 4 day sun habits diary. On two occasions, researchers assessed observable sun protection behaviors (wearing hats, shirts, sunglasses), swabbed the skin to detect the presence of sunscreen, and subjects wore polysulphone dosimeters to measure UVR exposure. Overall, observed sun protection behaviors were more highly correlated with diary reports than with survey reports. While lifeguards and children reported spending comparable amounts of time in the sun, dosimeter measures showed that lifeguards received twice as much UVR exposure. This study demonstrated the feasibility of implementing a multimethod validity study within a broader population of swimming pools.

Review of the Global Solar UV Index 2015 Workshop Report.

The Global Solar UV Index was developed as an easy-to-understand measure of the amount of biologically-effective ambient solar ultraviolet radiation (UVR) at different locations on the earth's surface. Over the past few years, questions have been raised about the global applicability of the UV Index, about the evidence base for exposure risk thresholds and related protective measures, and about whether the overall impact of the UV Index could be improved with modifications. An international workshop was organized by several organizations, including the World Health Organization, to assess if current evidence was sufficiently strong to modify the UV Index and to discuss different ways it might be improved in order to influence sun-protective behavior. While some animal research suggests there may be no threshold effect, the relative importance of sub-erythemal doses of sunlight in causing skin cancer in humans remains unknown. Evidence suggests that regular use of sunscreen can prevent skin cancer and that sunglasses are an effective method of protecting the eyes from solar UVR. The UV Index as a risk communication tool continues to be useful for raising awareness and to support sun-protection behavior. Although there was agreement that guidance on the use of the UV Index could be improved, the workshop participants identified that strong health outcome-based human evidence would be needed as the basis for a revision. For the UV Index to be relevant in as many countries as possible, it should continue to be adapted to suit local conditions.

Assessment of the UVR protection provided by different tree species.

In recent years, SunSmart campaigns have emphasized the importance of the use of shade as a strategy in the reduction of human exposure to solar UV radiation (UVR), particularly in early life with the provision of shade in schools. Trees can play an important role in shade provision, either as the main shade provider or to augment shade structures and increase UVR protection provided to the general population. A study to measure the protection provided by a range of trees common in Australian urban environments was undertaken during the summers of 2004/2005 and 2005/2006. Solar UVR beneath the trees was measured using UVR sensitive polysulphone badges positioned horizontally within the shaded area and were compared with those in full sunshine to give an indication of the protection provided. Measurements made on sunny days during the months of October to April indicated that the shade cover provided by the trees depended upon the tree species and changed with season as a result of changing foliage and sun angles. Measured protection factors ranged from 5 to 10 and were generally a maximum in the height of summer when the sun was highest in the sky and the foliage was densest.

Measurements of the UVR protection provided by hats used at school.

The importance of protection against solar ultraviolet radiation (UVR) in childhood has lead to SunSmart policies at Australian schools, in particular primary schools, where children are encouraged and in many cases required to wear hats at school. Hat styles change regularly and the UVR protection provided by some of the hat types currently used and recommended for sun protection by the various Australian state cancer councils had not been previously evaluated. The UVR protection of the hats was measured using UVR sensitive polysulphone film badges attached to different facial sites on rotating headforms. The sun protection type hats included in this study were broad-brimmed hats, "bucket hats" and legionnaires hats. Baseball caps, which are very popular, were also included. The broad-brimmed hats and bucket hats provided the most UVR protection for the six different sites about the face and head. Legionnaires hats also provided satisfactory UVR protection, but the caps did not provide UVR protection to many of the facial sites. The highest measured UVR protection factors for facial sites other than the forehead were 8 to 10, indicating that, while some hats can be effective, they need to be used in combination with other forms of UVR protection.

Comparing Handheld Meters and Electronic Dosimeters for Measuring Ultraviolet Levels under Shade and in the Sun.

This study aimed to compare the validity, reliability and practicality of alternative portable methods for measuring erythemal UVR levels in passive recreation areas in public parks. UVR levels were measured for point in time comparisons between Solarmeter 6.5 handheld meters and time-stamped electronic dosimeters in a large central park in Melbourne, Australia. Observations were made at 20 locations in the park by two research assistants under two conditions: (1) matched shade (2) contrasting shade-no shade. Comparisons were also made with scientific instruments on the UVR monitoring station rooftop and by remotely selecting UV records and forecasts on cloud-free dates of park observations. There was good agreement between the portable UVR instruments in the park setting as confirmed via Bland Altman plots, while the dosimeter appeared less sensitive to change in shade conditions. The rooftop measurements showed that the Solarmeter 6.5 UVR readings were comparable to those of the adjacent rooftop instruments. The practicalities of using the dosimeters and Solarmeters for behavioral studies are discussed. These findings provide a basis for use of the Solarmeter 6.5 to measure changes in UVR levels due to different environmental conditions with relative accuracy for intervention studies in outdoor settings.

International Intercomparison of Solar UVR Spectral Measurement Systems in Melbourne in 2013.

Monitoring ambient solar UVR levels provides information on how much there is in both real time and historically. Quality assurance of ambient measurements of solar UVR is critical to ensuring accuracy and stability and this can be achieved by regular intercomparisons of spectral measurement systems with those of other organizations. In October and November of 2013 a solar UVR spectroradiometer from Public Health England (PHE) was brought to Melbourne for a campaign of intercomparisons with a new Bentham spectrometer of Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) and one at the Australian Bureau of Meteorology (BOM), supported by New Zealand's National Institute for Water and Atmosphere (NIWA). Given all three spectroradiometers have calibrations that are traceable to various national standards, the intercomparison provides a chance to determine measurement uncertainties and traceability that support UV measurement networks in Australia, New Zealand and the UK. UV Index measurements from all three systems were compared and ratios determined for clear sky conditions when the scans from each instrument were within 2 min of each other. While wavelengths below 305 nm showed substantial differences between the PHE unit and the two other systems, overall the intercomparison results were encouraging, with mean differences in measured UV Index between the BOM/NIWA and those of PHE and ARPANSA of <0.1% and 7.5%, respectively.

Sun protective clothing: 5 years of experience in Australia.

The Australian/New Zealand Standard AS/NZS 4399 "Sun protective clothing--evaluation and classification" was published in 1996. AS/NZS 4399 has been well accepted and most companies wishing to claim UVR protection for their products have complied with the labeling requirements. This standard is not mandatory, unlike two other Australian standards dealing with solar ultraviolet radiation (UVR) protection, namely the Sunscreen Standard (AS2604) and the Sunglass Standard (AS1067). With these standards there is the ability to impose substantial penalties for non-compliance. In Australia the standard-setting process is achieved by consensus and the development of AS/NZS 4399 was a long and involved process which took a number of years. The standard is not perfect; it was appreciated that issues such as garment lifetime and stretch and wet testing needed to be covered and it was planned to address these in a revised standard. In the 5 years since publication considerable work, in both Australia and overseas, has been carried out. Other national standards have been developed and published. This paper presents some of the rationale which the committee worked through prior to 1996. Also covered are many of the experiences and difficulties in the 5 years since the introduction of AS/NZS 4399, in particular the effect of local conditions and legal requirements on the operation of the standard.

Measured solar ultraviolet radiation exposures of outdoor workers in Queensland in the building and construction industry.

The risk to outdoor workers of exposure to solar ultraviolet radiation (UVR) has been known for some time, particularly in the building and construction industry, where workers often use little in the way of protection against solar UVR. In recent years there have been attempts by authorities in Australia and in Queensland in particular, where UVR levels in spring and summer are very high to extreme, to instigate and to encourage the use of personal UVR protection by outdoor workers. To quantify UVR exposure of building and construction industry workers involved in typical outdoor work, a study was conducted using UVR-sensitive polysulphone film badges. The results indicated that the doses were significant, often well in excess of recommended exposure limits. The measured exposures varied between trades. Data on the use of personal UVR-protective equipment and the skin type of workers were also collected. Many of the workers had skin types that were sensitive to UVR and showed signs of sunburn. In summary, the study found that at-risk individuals were exposed to extreme levels of UVR, in most cases without adequate and appropriate sun protection.

Measurements of the solar UVR protection provided by shade structures in New Zealand primary schools.

To reduce ultraviolet radiation (UVR) exposure during childhood, shade structures are being erected in primary schools to provide areas where children can more safely undertake outdoor activities. This study to evaluate the effectiveness of existing and purpose built shade structures in providing solar UVR protection was carried out on 29 such structures in 10 schools in New Zealand. Measurements of the direct and scattered solar UVR doses within the central region of the shade structures were made during the school lunch break period using UVR-sensitive polysulfone film badges. These measurements indicate that many of the structures had UVR protection factors (PF) of 4-8, which was sufficient to provide protection during the school lunch hour. However, of the 29 structures examined, only six would meet the suggested requirements of UVR PF greater than 15 required to provide all-day protection.

Global Solar UV Index: Australian measurements, forecasts and comparison with the UK.

The 2002 revision of the UV index (UVI) issued by the World Health Organisation (WHO), the World Meteorological Office (WMO), the United Nations Environment Programme (UNEP) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP) (World Health Organization [2002] Global Solar UV Index: A Practical Guide. WHO, Geneva) was motivated by the need to further standardize the use and presentation of the UVI. Awareness of the hazards of solar UV radiation (UVR) is generally high in Australia, but more effective use of the UVI will assist in promoting further changes to the population's sun exposure behavior. UVI levels for a number of cities around Australia as measured by the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), covering the time period 1996-2000, are presented. Also shown are UVI forecasts from the Australian Bureau of Meteorology (BOM). Agreement between the BOM data and the measurements varies depending on the location but is within 2 UVI units approximately 75% of the time. UVI levels are supplied to the media, and in summer values in excess of 12-14 are regularly recorded, although the more northerly locations occasionally reach 16 and 17. The factors affecting the solar UVR environment and the measured UVI are also discussed and compared against measurements from the UK.

Ultraviolet protection factors for clothing: an intercomparison of measurement systems.

In recent years the need to standardize measurement protocols for quantifying the degree of ultraviolet radiation (UVR) protection provided by clothing has led to the introduction of a number of standards around the world. To date, these standards have specified spectral measurements of UVR transmission by clothing and fabrics. Development of a standard test method has become an important part of the testing process, and this article presents results from an intercomparison involving 10 independent testing laboratories and 11 different UVR transmission measurement instruments. In addition to comparing the measured ultraviolet protection factors (UPF), this intercomparison also incorporates detailed scan results from all 10 laboratories and highlights differences in performance of the various instruments in different wavelength regions. Careful examination of these differences can indicate where changes to the systems could be made to allow improvements both in equipment performance and in agreement of the final results. The variability in the measurements of UPF in this study suggest that the protection categories in standards may need to be broadened.

Sun exposure and vitamin D status as Northeast Asian migrants become acculturated to life in Australia.

Vitamin D deficiency is more common in Northeast-Asian immigrants to western countries than in the local population; prevalence equalizes as immigrants adopt the host country's culture. In a community-based study of 100 Northeast-Asian immigrants in Canberra, Australia, we examined predictors of vitamin D status, its association with indicators of acculturation (English language use; time since migration) and mediators of that association. Participants completed a sun and physical activity diary and wore an electronic ultraviolet radiation (UVR) dosimeter for 7 days. Skin colour was measured by reflectance spectrophotometry. Serum concentrations of 25-hydroxyvitamin D (25(OH)D) and cardio-metabolic biomarkers were measured on fasting blood. In a multiple linear regression model, predictors for 25(OH)D concentration were season of blood collection, vitamin D supplementation, UVR exposure, body mass index, physical activity and having private health insurance (R(2) = 0.57). Greater acculturation was associated with lower risk of vitamin D deficiency (de-seasonalized 25(OH)D level <50 nmol L(-1)) (Adjusted Odds Ratio (AOR): 0.22 [95%CI 0.04-0.96]); this association was statistically mediated by physical activity and time outdoors. Vitamin D deficiency was associated with higher total cholesterol levels (>5.0 mmol L(-1)) (AOR: 7.48 [95%CI 1.51-37.0]). Targeted public health approaches are required to manage the high prevalence of vitamin D deficiency in migrants retaining a traditional lifestyle.