Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial

BACKGROUND: Trichuris suis ova is a probiotic treatment based on the hygiene hypothesis. It has been demonstrated as safe and effective in autoimmune inflammatory bowel diseases and clinical trials indicate that helminth infections also have an immunomodulatory effect in multiple sclerosis.We hypothesize that administering 2,500 Trichuris suis ova eggs orally every two weeks for 12 months is--due to its immunomodulatory and anti-inflammatory effect--significantly more effective than oral placebo in preventing new T2 and Gd+ lesions, as quantified by cerebral MRI and clinical examination, in relapsing-remitting multiple sclerosis and clinically isolated syndrome. METHODS/DESIGN: Fifty patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome with clinical activity, not undergoing any standard therapies, will be randomized 1:1 to Trichuris suis ova 2,500 eggs every two weeks or matching placebo. The safety, tolerability and effect on disease activity and in vivo mechanisms of action of Trichuris suis ova in MS will be assessed by neurological, laboratory and immunological exams and magnetic resonance imaging throughout the 12-month treatment period and over a follow-up period of 6 months. Various immunological analyses will be used to assess the overall patient immune response prior to and at varying time points following treatment with Trichuris suis ova. DISCUSSION: We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01413243

Gathering the evidence and identifying opportunities for future research in climate, heat and health in South Africa : the role of the South African Medical Research Council

Abstract: Background. A changing climate is likely to have widespread and varying impacts on ecosystems and human health. South Africa (SA) is particularly vulnerable to the impacts of climate change, given the projected increases in temperature, and changes in the amount and patterns of rainfall. Moreover, SA’s vulnerability is exacerbated by extreme inequality and poverty. To prepare for the impacts of climate change and to ensure timeous adaptation, a perspective is given on essential heat and health research in the country. Objectives. To gather studies conducted by the South African Medical Research Council (SAMRC)’s Environment and Health Research Unit (EHRU) to illustrate the range of possible research key areas in the climate, heat and health domain and to present future research priorities. Methods. Studies conducted by the SAMRC’s EHRU were gathered and used to illustrate the range of possible research key areas in the climate, heat and health domain. Using national and international published and grey literature, and tapping into institutional research experiences, an overview of research findings to date and future research priorities were developed. Results. Heat and health-related research has focussed on key settings, for example, schools, homes and outdoor work places, and vulnerable groups such as infants and children, the elderly and people with pre-existing diseases. The need to address basic needs and services provision was emphasised as an important priority. Conclusions. High and low temperatures in SA are already associated with mortality annually; these impacts are likely to increase with a changing climate. Critical cross-sectoral research will aid in understanding and preparing for temperature extremes in SA

Indoor and outdoor particulate matter concentrations on the Mpumalanga highveld – A case study

The household combustion of solid fuels, for the purpose of heating and cooking, is an activity practiced by many people in South Africa. Air pollution caused by the combustion of solid fuels in households has a significant influence on public health. People mostaffected are those considered to be the poorest, living in low-income settlements, where burning solid fuel is the primary source of energy. Insufficient data has been collected in South Africa to quantify the concentrations of particulate emissions that peopleare exposed to, especially the respirable fraction, associated with the combustion of solid fuels. The aim of this paper is to gain an understanding of the particulate matter (PM) concentrations a person living in a typical household in a low income settlement in theSouth African Highveld is exposed to. It also seeks to demonstrate that the use of solid fuels in the household can lead to indoor air pollution concentrations reaching levels very similar to ambient PM concentrations, which could be well in excess of the NationalAmbient Air Quality Standards, representing a major national public health threat. A mobile monitoring station was used in KwaDela, Mpumalanga to measure both ambient particulate concentrations and meteorological conditions, while a range of dust/particulate monitors were used for indoor and personal particulate concentration measurements. Indoor and personal measurements are limited to the respirable fraction (PM4) as this fraction contributes significantly to the negative health impacts. The sampling for this case study took place from 7-19 August 2014. Highest particulate matter concentrations were evident during the early mornings and the early evenings, when solid fuel burning activities were at their highest. Indoor and personal daily average PM4 concentrations did not exceed the 24h National Ambient PM2.5 Standard of 65 μg/m3 nor did they exceed the 24h National Ambient PM10 Standard of 75 μg/ m3. The outdoor PM2.5 concentrations were found to be below the standards for the duration of the sampling period. The outdoor PM10 concentrations exceeded the standards for one day during the sampling period. Results indicate that, although people in KwaDelamay be exposed to ambient PM concentrations that can be non-compliant to ambient standards, the exposure to indoor air, where solid fuel is burnt, may be detrimental to their health

Multi-Frequency Synthesis of VLBI Images Using a Generalized Maximum Entropy Method

A new multi-frequency synthesis algorithm for reconstructing images from multi-frequency VLBI data is proposed. The algorithm is based on a generalized maximum-entropy method, and makes it possible to derive an effective spectral correction for images over a broad frequency bandwidth, while simultaneously reconstructing the spectral-index distribution over the source. The results of numerical simulations demonstrating the capabilities of the algorithm are presented.Comment: 17 pages, 8 figure

Disease modification in multiple sclerosis by flupirtine-results of a randomized placebo controlled phase II trial

Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less accessible to treatment. Based on suggested additional neuroprotective capacities of the orally available non-opioid and centrally acting analgesic drug flupirtine maleate we hypothesized that treatment with flupirtine maleate might be beneficial in MS patients. The flupirtine as oral treatment in multiple sclerosis (FLORIMS) study was a multi-center, randomized and stratified, placebo-controlled double-blind phase II trial to investigate safety and efficacy in terms of clinical and radiographical activity of flupirtine maleate (300 mg per day) given orally for 12 months, add-on to interferon beta 1b subcutaneously in patients with relapsing remitting MS. Due to a substantial delay in recruitment, enrolment of patients was prematurely terminated after randomization of only 30 of the originally planned 80 patients. Of these, 24 regularly terminated study after 12 months of treatment. Data were analyzed as originally planned. Treatment with flupirtine maleate was overall well tolerated. We observed moderate and asymptomatic elevations of liver enzymes in several cases but no overt hepatotoxicity. Neither the intention to treat nor the per protocol analysis revealed any significant treatment effects of flupirtine maleate with respect to occurrence of MS relapses, disability progression, or development of new lesions on cranial MRI. However, substantial methodological limitations need to be considered when interpreting these results. In conclusion, the results of the FLORIMS study neither add further evidence to nor argue against the hypothesized neuroprotective or disease modifying effects of flupirtine maleate in MS

Quantifying the Impact of Bedrock Topography Uncertainty in Pine Island Glacier Projections for This Century

Abstract: The predicted Antarctic contribution to global‐mean sea‐level rise is one of the most uncertain among all major sources. Partly this is because of instability mechanisms of the ice flow over deep basins. Errors in bedrock topography can substantially impact the projected resilience of glaciers against such instabilities. Here we analyze the Pine Island Glacier topography to derive a statistical model representation. Our model allows for inhomogeneous and spatially dependent uncertainties and avoids unnecessary smoothing from spatial averaging or interpolation. A set of topography realizations is generated representing our best estimate of the topographic uncertainty in ice sheet model simulations. The bedrock uncertainty alone creates a 5%–25% uncertainty in the predicted sea level rise contribution at year 2100, depending on friction law and climate forcing. Pine Island Glacier simulations on this new set are consistent with simulations on the BedMachine reference topography but diverge from Bedmap2 simulations

GHQ increases among Scottish 15 year olds 1987–2006

BACKGROUND: Increases in a number of psychosocial disorders have been identified among Western youth in the second half of the Twentieth century. However findings are not consistent, trends are complex, and comparisons over time are hampered by methodological problems. METHODS: Data were drawn from three samples identical in respect of age (15 years), school year (final year of statutory schooling) and geographical location (the West of Scotland). Each sample was administered the 12-item General Health Questionnaire, a measure of self-report psychological distress, in 1987 (N = 505), 1999 (N = 2,196) and 2006 (N = 3,194). Analyses were conducted to examine changes in: GHQ 'caseness'; individual items; and factors, derived via confirmatory factor analysis representing (a) 'negative' and 'positive' items, and (b) 'anxiety and depression', 'loss of confidence or self-esteem' and 'anhedonia and social dysfunction'. RESULTS: Based on the standard (2/3) cut-off, 'caseness' rates in 1987, 1999 and 2006 were 12.7, 15.1 and 21.5% (males) and 18.8, 32.5 and 44.1% (females). Similar increases were observed with more stringent 'caseness' cut-offs. Examination of individual items showed some to have increased much more markedly over time than others. There were larger increases among females for all except two items and some evidence, among both genders, of steeper increases among 'negative' items compared with 'positive' ones. However, the differences in slope were very small compared with the overall increases in both types. CONCLUSIONS: Data from three samples identical in respect of age, school year and geographical location, show marked increases in GHQ-12 'caseness' among females between 1987 and 1999 and among both males and females between 1999 and 2006. Although slightly steeper increases in 'negative' items raise the possibility that endorsing such symptoms may have become more acceptable, these were small in comparison with increases in all dimensions of psychological distress. The next step is to identify causal explanations for the increases reported here

Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis

BACKGROUND:Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS:Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-beta) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months -2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-beta comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-beta comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-beta comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-beta comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE:Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-beta, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION:ClinicalTrials.gov NCT00616187