Factors associated with clinical leptospirosis: a population-based case-control study in the Seychelles (Indian Ocean).

BACKGROUND: In Western countries, leptospirosis is uncommon and mainly occurs in farmers and individuals indulging in water-related activities. In tropical countries, leptospirosis can be up to 1000 times more frequent and risk factors for this often severe disease may differ. METHODS: We conducted a one-year population-based matched case-control study to investigate the frequency and associated factors of leptospirosis in the entire population of Seychelles. RESULTS: A total of 75 patients had definite acute leptospirosis based on microagglutination test (MAT) and polymerase chain reaction (PCR) assay (incidence: 101 per 100,000 per year; 95% confidence interval [CI]: 79-126). Among the controls, MAT was positive in 37% (past infection) and PCR assay in 9% (subclinical infection) of men aged 25-64 with manual occupation. Comparing cases and controls with negative MAT and PCR, leptospirosis was associated positively with walking barefoot around the home, washing in streams, gardening, activities in forests, alcohol consumption, rainfall, wet soil around the home, refuse around the home, rats visible around the home during day time, cats in the home, skin wounds and inversely with indoor occupation. The considered factors accounted for as much as 57% of the variance in predicting the disease. CONCLUSION: These data indicate a high incidence of leptospirosis in Seychelles. This suggests that leptospires are likely to be ubiquitous and that effective leptospirosis control in tropical countries needs a multifactorial approach including major behaviour change by large segments of the general public.

Climate-based empirical models show biased predictions of butterfly communities along environmental gradients

A better understanding of the factors that mould ecological community structure is required to accurately predict community composition and to anticipate threats to ecosystems due to global changes. We tested how well stacked climate-based species distribution models (S-SDMs) could predict butterfly communities in a mountain region. It has been suggested that climate is the main force driving butterfly distribution and community structure in mountain environments, and that, as a consequence, climate-based S-SDMs should yield unbiased predictions. In contrast to this expectation, at lower altitudes, climate-based S-SDMs overpredicted butterfly species richness at sites with low plant species richness and underpredicted species richness at sites with high plant species richness. According to two indices of composition accuracy, the Sorensen index and a matching coefficient considering both absences and presences, S-SDMs were more accurate in plant-rich grasslands. Butterflies display strong and often specialised trophic interactions with plants. At lower altitudes, where land use is more intense, considering climate alone without accounting for land use influences on grassland plant richness leads to erroneous predictions of butterfly presences and absences. In contrast, at higher altitudes, where climate is the main force filtering communities, there were fewer differences between observed and predicted butterfly richness. At high altitudes, even if stochastic processes decrease the accuracy of predictions of presence, climate-based S-SDMs are able to better filter out butterfly species that are unable to cope with severe climatic conditions, providing more accurate predictions of absences. Our results suggest that predictions should account for plants in disturbed habitats at lower altitudes but that stochastic processes and heterogeneity at high altitudes may limit prediction success of climate-based S-SDMs.

Rehabilitation needs assessment in persons with spinal cord injury following the 2010 earthquake in Haiti: a pilot study using an ICF-based tool.

OBJECTIVE: The aim of this pilot study was to describe problems in functioning and associated rehabilitation needs in persons with spinal cord injury after the 2010 earthquake in Haiti by applying a newly developed tool based on the International Classification of Functioning, Disability and Health (ICF). DESIGN: Pilot study. SUBJECTS: Eighteen persons with spinal cord injury (11 women, 7 men) participated in the needs assessment. Eleven patients had complete lesions (American Spinal Injury Association Impairment Scale; AIS A), one patient had tetraplegia. METHODS: Data collection included information from the International Spinal Cord Injury Core Data Set and a newly developed needs assessment tool based on ICF Core Sets. This tool assesses the level of functioning, the corresponding rehabilitation need, and required health professional. Data were summarized using descriptive statistics. RESULTS: In body functions and body structures, patients showed typical problems following spinal cord injury. Nearly all patients showed limitations and restrictions in their activities and participation related to mobility, self-care and aspects of social integration. Several environmental factors presented barriers to these limitations and restrictions. However, the availability of products and social support were identified as facilitators. Rehabilitation needs were identified in nearly all aspects of functioning. To address these needs, a multidisciplinary approach would be needed. CONCLUSION: This ICF-based needs assessment provided useful information for rehabilitation planning in the context of natural disaster. Future studies are required to test and, if necessary, adapt the assessment.

Semi-supervised segmentation of ultrasound images based on patch representation and continuous min cut.

Ultrasound segmentation is a challenging problem due to the inherent speckle and some artifacts like shadows, attenuation and signal dropout. Existing methods need to include strong priors like shape priors or analytical intensity models to succeed in the segmentation. However, such priors tend to limit these methods to a specific target or imaging settings, and they are not always applicable to pathological cases. This work introduces a semi-supervised segmentation framework for ultrasound imaging that alleviates the limitation of fully automatic segmentation, that is, it is applicable to any kind of target and imaging settings. Our methodology uses a graph of image patches to represent the ultrasound image and user-assisted initialization with labels, which acts as soft priors. The segmentation problem is formulated as a continuous minimum cut problem and solved with an efficient optimization algorithm. We validate our segmentation framework on clinical ultrasound imaging (prostate, fetus, and tumors of the liver and eye). We obtain high similarity agreement with the ground truth provided by medical expert delineations in all applications (94% DICE values in average) and the proposed algorithm performs favorably with the literature.

Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study).

OBJECTIVE: The associations between inflammation, diabetes and insulin resistance remain controversial. Hence, we assessed the associations between diabetes, insulin resistance (using HOMA-IR) and metabolic syndrome with the inflammatory markers high-sensitive C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand eight hundred and eighty-four men and 3201 women, aged 35-75, participated in this study. METHODS: C-reactive protein was assessed by immunoassay and cytokines by multiplexed flow cytometric assay. In a subgroup of 532 participants, an oral glucose tolerance test (OGTT) was performed to screen for impaired glucose tolerance (IGT). RESULTS: IL-6, TNF-α and hs-CRP were significantly and positively correlated with fasting plasma glucose (FPG), insulin and HOMA-IR. Participants with diabetes had higher IL-6, TNF-α and hs-CRP levels than participants without diabetes; this difference persisted for hs-CRP after multivariate adjustment. Participants with metabolic syndrome had increased IL-6, TNF-α and hs-CRP levels; these differences persisted after multivariate adjustment. Participants in the highest quartile of HOMA-IR had increased IL-6, TNF-α and hs-CRP levels; these differences persisted for TNF-α and hs-CRP after multivariate adjustment. No association was found between IL-1β levels and all diabetes and insulin resistance markers studied. Finally, participants with IGT had higher hs-CRP levels than participants with a normal OGTT, but this difference disappeared after controlling for body mass index (BMI). CONCLUSION: We found that subjects with diabetes, metabolic syndrome and increased insulin resistance had increased levels of IL6, TNF-α and hs-CRP, while no association was found with IL-1β. The increased inflammatory state of subjects with IGT is partially explained by increased BMI.

Dosing regimen of gentamicin in neonates: evaluation of current guidelines based on a large population pharmacokinetic analysis

Objectives: Gentamicin is among the most commonly prescribed antibiotics in newborns, but large interindividual variability in exposure levels exists. Based on a population pharmacokinetic analysis of a cohort of unselected neonates, we aimed to validate current dosing recommendations from a recent reference guideline (Neofax®). Methods: From 3039 concentrations collected in 994 preterm (median gestational age 32.3 weeks, range 24.2-36.5) and 455 term newborns, treated at the University Hospital of Lausanne between 2006 and 2011, a population pharmacokinetic analysis was performed with NONMEM®. Model-based simulations were used to assess the ability of dosing regimens to bring concentrations into targets: trough ≤ 1mg/L and peak ~ 8mg/L. Results: A two-compartment model best characterized gentamicin pharmacokinetics. Model parameters are presented in the table. Body weight, gestational age and postnatal age positively influence clearance, which decreases under dopamine administration. Body weight and gestational age influence the distribution volume. Model based simulations confirm that preterm infants need doses superior to 4 mg/kg, and extended dosage intervals, up to 48 hours for very preterm newborns, whereas most term newborns would achieve adequate exposure under 4 mg/kg q. 24 h. More than 90% of neonates would achieve trough concentrations below 2 mg/L and peaks above 6 mg/L following most recent guidelines. Conclusions: Simulated gentamicin exposure demonstrates good accordance with recent dosing recommendations for target concentration achievement.

Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

BACKGROUND: Synthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen. METHODS: Individual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen. RESULTS: The combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing. CONCLUSIONS: The hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human. TRIAL REGISTRATION: ClinicalTrials.gov NCT01719133.

Urinary sphincter based on electronics and artificial muscles

Objectives: The AMS 800TM is the current artificial urinary sphincter (AUS) for incontinence due to intrinsic sphincter deficiency. Despite good clinical results, technical failures inherent to the hydraulic mechanism or urethral ischemic injury contribute to revisions up to 60%. We are developing an electronic AUS, called ARTUS to overcome the rigors of AMS. The objective of this study was to evaluate the technical efficacy and tissue tolerance of the ARTUS system in an animal model.Methods: The ARTUS is composed by three parts: the contractile unit, a series of rings and an integrated microprocessor. The contractile unit is made of Nitinol fibers. The rings are placed around the urethra to control the flow of urine by squeezing the urethra. They work in a sequential alternative mode and are controlled by a microprocessor. In the first phase a three-rings device was used while in the second phase a two-rings ARTUS was used. The device was implanted in 14 sheep divided in two groups of six and eight animals for study purpose. The first group aimed at bladder leak point pressure (BLPP) measurement and validation of the animal model; the second group aimed at verifying mid-term tissue tolerance by explants at twelve weeks. General animal tolerance was also evaluated.Results: The ARTUS system implantation was uneventful. When the system was activated, the BLPP was measured at 1.038±0.044 bar (mean±SD). Urethral tissue analysis did not show significant morphological changes. No infection and no sign of discomfort were noted in animals at 12 weeks.Conclusions: The ARTUS proved to be effective in continence achievement in this study. Histological results support our idea that a sequential alternative mode can avoid urethral atrophy and ischemia. Further technical developments are needed to verify long-term outcome and permit human use.

Predictors of nonresponse in a questionnaire-based outcome study of vocational rehabilitation patients.

OBJECTIVE: To identify predictors of nonresponse to a self-report study of patients with orthopedic trauma hospitalized for vocational rehabilitation between November 15, 2003, and December 31, 2005. The role of biopsychosocial complexity, assessed using the INTERMED, was of particular interest. DESIGN: Cohort study. Questionnaires with quality of life, sociodemographic, and job-related questions were given to patients at hospitalization and 1 year after discharge. Sociodemographic data, biopsychosocial complexity, and presence of comorbidity were available at hospitalization (baseline) for all eligible patients. Logistic regression models were used to test a number of baseline variables as potential predictors of nonresponse to the questionnaires at each of the 2 time points. SETTING: Rehabilitation clinic. PARTICIPANTS: Patients (N=990) hospitalized for vocational rehabilitation over a period of 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Nonresponse to the questionnaires was the binary dependent variable. RESULTS: Patients with high biopsychosocial complexity, foreign native language, or low educational level were less likely to respond at both time points. Younger patients were less likely to respond at 1 year. Those living in a stable partnership were less likely than singles to respond at hospitalization. Sex, psychiatric, and somatic comorbidity and alcoholism were never associated with nonresponse. CONCLUSIONS: We stress the importance of assessing biopsychosocial complexity to predict nonresponse. Furthermore, the factors we found to be predictive of nonresponse are also known to influence treatment outcome and vocational rehabilitation. Therefore, it is important to increase the response rate of the groups of concern in order to reduce selection bias in epidemiologic investigations.

Volumetric quantification of atherosclerotic plaque in CT considering partial volume effect.

Coronary artery calcification (CAC) is quantified based on a computed tomography (CT) scan image. A calcified region is identified. Modified expectation maximization (MEM) of a statistical model for the calcified and background material is used to estimate the partial calcium content of the voxels. The algorithm limits the region over which MEM is performed. By using MEM, the statistical properties of the model are iteratively updated based on the calculated resultant calcium distribution from the previous iteration. The estimated statistical properties are used to generate a map of the partial calcium content in the calcified region. The volume of calcium in the calcified region is determined based on the map. The experimental results on a cardiac phantom, scanned 90 times using 15 different protocols, demonstrate that the proposed method is less sensitive to partial volume effect and noise, with average error of 9.5% (standard deviation (SD) of 5-7mm(3)) compared with 67% (SD of 3-20mm(3)) for conventional techniques. The high reproducibility of the proposed method for 35 patients, scanned twice using the same protocol at a minimum interval of 10 min, shows that the method provides 2-3 times lower interscan variation than conventional techniques.

The mzTab Data Exchange Format: Communicating Mass-spectrometry-based Proteomics and Metabolomics Experimental Results to a Wider Audience.

The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R. We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online.