Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

\ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment

Molecular Dynamics Analysis of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism for Selective Oxidation of Met-93

Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown. Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus providing a plausible mechanism by which eicosatetraenoic acids bearing hydroperoxides on different carbon atoms can interact with Met93 to yield Met93 sulfoxide (Met93SO). Simulations of glycosylated apoD indicated that a second solvent exposed Met at position 49 was shielded by a triantennerary N-glycan attached to Asn45 thereby precluding lipid interactions. MD simulations of apoD showed B-factors of the loop containing Met93SO were higher in the oxidized protein, indicating increased flexibility that is predicted to destabilize the protein and promote self-association. Conclusions/Significance: These studies provide novel insights into the mechanisms that may contribute to the antioxidant function of apoD and the structural consequences that result if Met93SO is not redox-cycled back to its native state

Seafloor character and sedimentary processes in eastern Long Island Sound and western Block Island Sound

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Geo-Marine Letters 26 (2006): 59-68, doi: 10.1007/s00367-006-0016-4.Multibeam bathymetric data and seismic-reflection profiles collected in eastern Long Island and western Block Island Sounds reveal previously unrecognized glacial features and modern bedforms. Glacial features include an ice-sculptured bedrock surface, a newly identified recessional moraine, exposed glaciolacustrine sediments, and remnants of stagnant-ice-contact deposits. Modern bedforms include fields of transverse sand waves, barchanoid waves, giant scour depressions, and pockmarks. Bedform asymmetry and scour around obstructions indicate that net sediment transport is westward across the northern par of the study area near Fishers Island and eastward across the southern par near Great Gull Island.This work was supported by the Coastal and Marine Geology Program of the U.S. Geological Survey, the Connecticut Department of Environmental Protection, and the Atlantic Hydrographic Branch of the National Oceanic and Atmospheric Administration

Application of multiple statistical tests to enhance mass spectrometry-based biomarker discovery

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry-based biomarker discovery has long been hampered by the difficulty in reconciling lists of discriminatory peaks identified by different laboratories for the same diseases studied. We describe a multi-statistical analysis procedure that combines several independent computational methods. This approach capitalizes on the strengths of each to analyze the same high-resolution mass spectral data set to discover consensus differential mass peaks that should be robust biomarkers for distinguishing between disease states.</p> <p>Results</p> <p>The proposed methodology was applied to a pilot narcolepsy study using logistic regression, hierarchical clustering, t-test, and CART. Consensus, differential mass peaks with high predictive power were identified across three of the four statistical platforms. Based on the diagnostic accuracy measures investigated, the performance of the consensus-peak model was a compromise between logistic regression and CART, which produced better models than hierarchical clustering and t-test. However, consensus peaks confer a higher level of confidence in their ability to distinguish between disease states since they do not represent peaks that are a result of biases to a particular statistical algorithm. Instead, they were selected as differential across differing data distribution assumptions, demonstrating their true discriminatory potential.</p> <p>Conclusion</p> <p>The methodology described here is applicable to any high-resolution MALDI mass spectrometry-derived data set with minimal mass drift which is essential for peak-to-peak comparison studies. Four statistical approaches with differing data distribution assumptions were applied to the same raw data set to obtain consensus peaks that were found to be statistically differential between the two groups compared. These consensus peaks demonstrated high diagnostic accuracy when used to form a predictive model as evaluated by receiver operating characteristics curve analysis. They should demonstrate a higher discriminatory ability as they are not biased to a particular algorithm. Thus, they are prime candidates for downstream identification and validation efforts.</p

The Reinforcing Therapist Performance (RTP) experiment: Study protocol for a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Rewarding provider performance has been recommended by the Institute of Medicine as an approach to improve the quality of treatment, yet little empirical research currently exists that has examined the effectiveness and cost-effectiveness of such approaches. The aim of this study is to test the effectiveness and cost-effectiveness of providing monetary incentives directly to therapists as a method to improve substance abuse treatment service delivery and subsequent client treatment outcomes.</p> <p>Design</p> <p>Using a cluster randomized design, substance abuse treatment therapists from across 29 sites were assigned by site to either an implementation as usual (IAU) or pay-for-performance (P4P) condition.</p> <p>Participants</p> <p>Substance abuse treatment therapists participating in a large dissemination and implementation initiative funded by the Center for Substance Abuse Treatment.</p> <p>Intervention</p> <p>Therapists in both conditions received comprehensive training and ongoing monitoring, coaching, and feedback. However, those in the P4P condition also were given the opportunity to earn monetary incentives for achieving two sets of measurable behaviors related to quality implementation of the treatment.</p> <p>Outcomes</p> <p>Effectiveness outcomes will focus on the impact of the monetary incentives to increase the proportion of adolescents who receive a targeted threshold level of treatment, months that therapists demonstrate monthly competency, and adolescents who are in recovery following treatment. Similarly, cost-effectiveness outcomes will focus on cost per adolescent receiving targeted threshold level of treatment, cost per month of demonstrated competence, and cost per adolescent in recovery.</p> <p>Trial Registration</p> <p>Trial Registration Number: NCT01016704</p

Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway

Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol) ethyl ether methacrylate-co-poly(ethylene glycol) methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly-N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth) even at high iron concentrations (6 mM), indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA) approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury

TECNOB: study design of a randomized controlled trial of a multidisciplinary telecare intervention for obese patients with type-2 diabetes

Obesity is one of the most important medical and public health problems of our time: it increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. METHODS/DESIGN: TECNOB (TEChnology for OBesity) is a comprehensive two-phase stepped down program enhanced by telemedicine for the long-term treatment of obese people with type 2 diabetes seeking intervention for weight loss. Its core features are the hospital-based intensive treatment (1-month), that consists of diet therapy, physical training and psychological counseling, and the continuity of care at home using new information and communication technologies (ICT) such as internet and mobile phones. The effectiveness of the TECNOB program compared with usual care (hospital-based treatment only) will be evaluated in a randomized controlled trial (RCT) with a 12-month follow-up. The primary outcome is weight in kilograms. Secondary outcome measures are energy expenditure measured using an electronic armband, glycated hemoglobin, binge eating, self-efficacy in eating and weight control, body satisfaction, healthy habit formation, disordered eating-related behaviors and cognitions, psychopathological symptoms and weight-related quality of life. Furthermore, the study will explore what behavioral and psychological variables are predictive of treatment success among those we have considered. DISCUSSION: The TECNOB study aims to inform the evidence-based knowledge of how telemedicine may enhance the effectiveness of clinical interventions for weight loss and related type-2 diabetes, and which type of obese patients may benefit the most from such interventions. Broadly, the study aims also to have a effect on the theoretical model behind the traditional health care service, in favor of a change towards a new "health care everywhere" approach

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Assessing the efficacy of the healthy eating and lifestyle programme (HELP) compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial

Background: The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life. Study Design/Method: The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life. Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions) or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted. 200 obese young people (13-17 years, body mass index > 98th centile for age and sex) will be recruited from primary care within the greater London area. The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care. The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex. The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in obese adolescents than enhanced standard care assessed at 6 and 12 months post baseline assessment. Improvement in quality of life predicts on-going lifestyle change and maximises the chances of long-term weight reduction. We will explore whether improvement in QOL may be intermediate on the pathway between the intervention and body mass index change