Approximate Inference for Robust Gaussian Process Regression

Gaussian process (GP) priors have been successfully used in non-parametric Bayesian regression and classification models. Inference can be performed analytically only for the regression model with Gaussian noise. For all other likelihood models inference is intractable and various approximation techniques have been proposed. In recent years expectation-propagation (EP) has been developed as a general method for approximate inference. This article provides a general summary of how expectation-propagation can be used for approximate inference in Gaussian process models. Furthermore we present a case study describing its implementation for a new robust variant of Gaussian process regression. To gain further insights into the quality of the EP approximation we present experiments in which we compare to results obtained by Markov chain Monte Carlo (MCMC) sampling

Assessing a risk tailored intervention to prevent disabling low back pain - protocol of a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although most patients with low back pain (LBP) recover within a few weeks a significant proportion has recurrent episodes or will develop chronic low back pain. Several mainly psychosocial risk factors for developing chronic LBP have been identified. However, effects of preventive interventions aiming at behavioural risk factors and unfavourable cognitions have yielded inconsistent results. Risk tailored interventions may provide a cost efficient and effective means to take systematic account of the individual risk factors but evidence is lacking.</p> <p>Methods/Design</p> <p>This study will be a cluster-randomised controlled trial comparing screening and a subsequent risk tailored intervention for patients with low back pain to prevent chronic low back pain compared to treatment as usual in primary care. A total of 600 patients from 20 practices in each study arm will be recruited in Berlin and Goettingen. The intervention comprises the following elements: Patients will be assigned to one of four risk groups based on a screening questionnaire. Subsequently they receive an educational intervention including information and counselling tailored to the risk group. A telephone/email consulting service for back pain related problems are offered independent of risk group assignment. The primary outcomes will be functional capacity and sick leave.</p> <p>Discussion</p> <p>This trial will evaluate the effectiveness of screening for risk factors for chronic low back pain followed by a risk tailored intervention to prevent chronic low back pain. This trial will contribute new evidence regarding the flexible use of individual physical and psychosocial risk factors in general practice.</p> <p>Trial registration</p> <p>ISRCTN 68205910</p

Use of complementary alternative medicine for low back pain consulting in general practice: a cohort study

<p>Abstract</p> <p>Background</p> <p>Although back pain is considered one of the most frequent reasons why patients seek complementary and alternative medical (CAM) therapies little is known on the extent patients are actually using CAM for back pain.</p> <p>Methods</p> <p>This is a post hoc analysis of a longitudinal prospective cohort study embedded in a RCT. General practitioners (GPs) recruited consecutively adult patients presenting with LBP. Data on physical function, on subjective mood, and on utilization of health services was collected at the first consultation and at follow-up telephone interviews for a period of twelve months</p> <p>Results</p> <p>A total of 691 (51%) respectively 928 (69%) out of 1,342 patients received one form of CAM depending on the definition. Local heat, massage, and spinal manipulation were the forms of CAM most commonly offered. Using CAM was associated with specialist care, chronic LBP and treatment in a rehabilitation facility. Receiving spinal manipulation, acupuncture or TENS was associated with consulting a GP providing these services. Apart from chronicity disease related factors like functional capacity or pain only showed weak or no association with receiving CAM.</p> <p>Conclusion</p> <p>The frequent use of CAM for LBP demonstrates that CAM is popular in patients and doctors alike. The observed association with a treatment in a rehabilitation facility or with specialist consultations rather reflects professional preferences of the physicians than a clear medical indication. The observed dependence on providers and provider related services, as well as a significant proportion receiving CAM that did not meet the so far established selection criteria suggests some arbitrary use of CAM.</p

TERRA Promotes Telomere Shortening through Exonuclease 1–Mediated Resection of Chromosome Ends

The long noncoding telomeric repeat containing RNA (TERRA) is expressed at chromosome ends. TERRA upregulation upon experimental manipulation or in ICF (immunodeficiency, centromeric instability, facial anomalies) patients correlates with short telomeres. To study the mechanism of telomere length control by TERRA in Saccharomyces cerevisiae, we mapped the transcriptional start site of TERRA at telomere 1L and inserted a doxycycline regulatable promoter upstream. Induction of TERRA transcription led to telomere shortening of 1L but not of other chromosome ends. TERRA interacts with the Exo1-inhibiting Ku70/80 complex, and deletion of EXO1 but not MRE11 fully suppressed the TERRA–mediated short telomere phenotype in presence and absence of telomerase. Thus TERRA transcription facilitates the 5′-3′ nuclease activity of Exo1 at chromosome ends, providing a means to regulate the telomere shortening rate. Thereby, telomere transcription can regulate cellular lifespan through modulation of chromosome end processing activities

Influence of Hyper-Alkaline pH Leachate on Mineral and Porosity Evolution in the Chemically Disturbed Zone Developed in the Near-Field Host Rock for a Nuclear Waste Repository

This paper evaluates the effect of hyper-alkaline (NaOH/KOH) leachate on the mineralogy and porosity of a generic quartzo-feldspathic host rock for intermediate- and low-level nuclear waste disposal following permeation of the cementitious repository barrier by groundwater. The analysis is made with reference to expected fluid compositions that may develop by contact of groundwater with the cementitious barrier to form a chemically disturbed zone (CDZ) in the adjacent host rock, as informed by relevant natural analogue sites. Theoretical analysis and numerical modelling is used to explore the influence of different host rock mineral assemblages on changes in pore fluid chemistry, multiple mineral dissolution and precipitation reactions and matrix porosity within the CDZ under these conditions. The numerical modelling accounts for kinetic and surface area effects on the mineral transformation and porosity development for periods of up to 10,000 years travel time from the repository and ambient temperature of 20∘C. The analysis shows that dissolution of quartz, feldspar and muscovite in the host rock, by the hyper-alkaline waste leachate, will create relatively high concentrations of dissolved Si and Al in the pore fluid, which migrates as chemical fronts within the CDZ. Precipitation of secondary mineral phases is predicted to occur under these conditions. The increase in matrix porosity that arises from dissolution of primary aluminosilicate minerals is compensated by a reduction in porosity due to precipitation of the secondary phases, but with a net overall increase in matrix porosity. These coupled physical and geochemical processes are most important for contaminant transport in the near-field zone of the CDZ and are eventually buffered by the host rock within 70 m of the repository for the 10,000 year travel time scenario. The predicted changes in matrix porosity may contribute to increased transport of radionuclides in the host rock, in the absence of attenuation by other mechanisms in the CDZ

Structural basis for the binding of IRES RNAs to the head of the ribosomal 40S subunit

Some viruses exploit internal initiation for their propagation in the host cell. This type of initiation is facilitated by structured elements (internal ribosome entry site, IRES) upstream of the initiator AUG and requires only a reduced number of canonical initiation factors. An important example are IRES of the virus family Dicistroviridae that bind to the inter-subunit side of the small ribosomal 40S subunit and lead to the formation of elongation-competent 80S ribosomes without the help of any initiation factor. Here, we present a comprehensive functional and structural analysis of eukaryotic-specific ribosomal protein rpS25 in the context of this type of initiation and propose a structural model explaining the essential involvement of rpS25 for hijacking the ribosome

Effect of a Simple Information Booklet on Pain Persistence after an Acute Episode of Low Back Pain: A Non-Randomized Trial in a Primary Care Setting

Mass-media campaigns have been known to modify the outcome of low back pain (LBP). We assessed the impact on outcome of standardized written information on LBP given to patients with acute LBP.A 3-month pragmatic, multicenter controlled trial with geographic stratification.Primary care practice in France.2752 patients with acute LBP.An advice book on LBP (the "back book").The main outcome measure was persistence of LBP three months after baseline evaluation.2337 (85%) patients were assessed at follow-up and 12.4% of participants reported persistent LBP. The absolute risk reduction of reporting persistent back pain in the intervention group was 3.6% lower than in the control group (10.5% vs. 14.1%; 95% confidence interval [-6.3% ; -1.0%]; p value adjusted for cluster effect = 0.01). Patients in the intervention group were more satisfied than those in the control group with the information they received about physical activities, when to consult their physician, and how to prevent a new episode of LBP. However, the number of patients who had taken sick leave was similar, as was the mean sick-leave duration, in both arms, and, among patients with persistent pain at follow-up, the intervention and control groups did not differ in disability or fear-avoidance beliefs.The level of improvement of an information booklet is modest, but the cost and complexity of the intervention is minimal. Therefore, the implications and generalizability of this intervention are substantial.ClinicalTrials.gov NCT00343057