Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index.

BACKGROUND The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach. METHODS Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations. RESULTS In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment. CONCLUSION The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments. TRIAL REGISTRATION Current Controlled Trials ISRCTN52023186.

Frequency and molecular characterisation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, and Entamoeba hartmanni in the context of water scarcity in northeastern Brazil

This study aimed to estimate the frequency, associated factors, and molecular characterisation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, andEntamoeba hartmanni infections. We performed a survey (n = 213 subjects) to obtain parasitological, sanitation, and sociodemographic data. Faecal samples were processed through flotation and centrifugation methods.E. histolytica, E. dispar, E. moshkovskii, and E. hartmanni were identified by nested-polymerase chain reaction (PCR). The overall prevalence of infection was 22/213 (10.3%). The infection rate among subjects who drink rainwater collected from roofs in tanks was higher than the rate in subjects who drink desalinated water pumped from wells; similarly, the infection rate among subjects who practice open defecation was significantly higher than that of subjects with latrines. Out of the 22 samples positive for morphologically indistinguishableEntamoeba species, the differentiation by PCR was successful for 21. The species distribution was as follows: 57.1% to E. dispar, 23.8% to E. histolytica, 14.3% toE. histolytica and E. dispar, and 4.8% E. dispar and E. hartmanni. These data suggest a high prevalence of asymptomatic infection by the group of morphologically indistinguishable Entamoeba histolytica/dispar/moshkovskiicomplex and E. hartmanni species. In this context of water scarcity, the sanitary and socioenvironmental characteristics of the region appear to favour transmission.

Multi-isotopic and compositional exploration of factors controlling nitrate pollution

In Catalonia, according to the nitrate directive (91/676/EU), nine areas have been declared as vulnerable to nitrate pollution from agricultural sources (Decret 283/1998 and Decret 479/2004). Five of these areas have been studied coupling hydro chemical data with a multi-isotopic approach (Vitòria et al. 2005, Otero et al. 2007, Puig et al. 2007), in an ongoing research project looking for an integrated application of classical hydrochemistry data, with a comprehensive isotopic characterisation (δ15N and δ18O of dissolved nitrate, δ34S and δ18O of dissolved sulphate, δ13C of dissolved inorganic carbon, and δD and δ18O of water). Within this general frame, the contribution presented explores compositional ways of: (i) distinguish agrochemicals and manure N pollution, (ii) quantify natural attenuation of nitrate (denitrification), and identify possible controlling factors.To achieve this two-fold goal, the following techniques have been used. Separate biplots of each suite of data show that each studied region has a distinct δ34S and pH signatures, but they are homogeneous with regard to NO3- related variables. Also, the geochemical variables were projected onto the compositional directions associated with the possible denitrification reactions in each region. The resulting balances can be plot together with some isotopes, to assess their likelihood of occurrence

Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Correcting non cephalic presentation with moxibustion: study protocol for a multi-centre randomised controlled trial in general practice.

BACKGROUND Non cephalic presentation in childbirth involves various risks to both the mother and the foetus. The incidence in Spain is 3.8% of all full-term pregnancies. The most common technique used to end the gestation in cases of non cephalic presentation is that of caesarian section, and although it provokes a lower rate of morbi-mortality than does vaginal delivery in such situations, there remains the possibility of traumatic injury to the foetal head and neck, while maternal morbidity is also increased. The application of heat (moxibustion) to an acupuncture point, in order to correct non cephalic presentation, has been practised in China since ancient times, but as yet there is insufficient evidence of its real effectiveness. METHODS/DESIGN The experimental design consists of a multi-centre randomised controlled trial with three parallel arms, used to compare real moxibustion, sham moxibustion and the natural course of events, among pregnant women with a non cephalic presentation and a gestational duration of 33-35 weeks (estimated by echography). The participants in the trial will be blinded to both interventions. The results obtained will be analyzed by professionals, blinded with respect to the allocation to the different types of intervention. In addition, we intend to carry out a economic analysis. DISCUSSION This trial will contribute to the development of evidence concerning moxibustion in the correction of non cephalic presentations. The primary outcome variable is the proportion of cephalic presentations at term. As secondary outcomes, we will evaluate the proportion of cephalic presentations at week 38 of gestation, determined by echography, together with the safety of the technique, the specificity of moxibustion and the control of the blinding process. This study has been funded by the Health Ministry of the Andalusian Regional Government. TRIAL REGISTRATION Current Controlled Trials ISRCTN10634508.

Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

INTRODUCTION Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

Multi-modal distraction: insights from children's limited attention.

How does the multi-sensory nature of stimuli influence information processing? Cognitive systems with limited selective attention can elucidate these processes. Six-year-olds, 11-year-olds and 20-year-olds engaged in a visual search task that required them to detect a pre-defined coloured shape under conditions of low or high visual perceptual load. On each trial, a peripheral distractor that could be either compatible or incompatible with the current target colour was presented either visually, auditorily or audiovisually. Unlike unimodal distractors, audiovisual distractors elicited reliable compatibility effects across the two levels of load in adults and in the older children, but high visual load significantly reduced distraction for all children, especially the youngest participants. This study provides the first demonstration that multi-sensory distraction has powerful effects on selective attention: Adults and older children alike allocate attention to potentially relevant information across multiple senses. However, poorer attentional resources can, paradoxically, shield the youngest children from the deleterious effects of multi-sensory distraction. Furthermore, we highlight how developmental research can enrich the understanding of distinct mechanisms controlling adult selective attention in multi-sensory environments.

The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-gamma production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation.

A three-pronged approach to social business: a Brazilian multi-case analysis

Social businesses present a new paradigm to capitalism, in which private companies, non-profit organizations and civil society create a new type of business with the main objective of solving social problems with financial sustainability and efficiency through market mechanisms. As any new phenomenon, different authors conceptualize social businesses with distinct views. This article aims to present and characterize three different perspectives of social business definitions: the European, the American and that of the emerging countries. Each one of these views was illustrated by a different Brazilian case. We conclude with the idea that all the cases have similar characteristics, but also relevant differences that are more than merely geographical. The perspectives analyzed in this paper provide an analytical framework for understanding the field of social businesses. Moreover, the cases demonstrate that in the Brazilian context the field of social business is under construction and that as such it draws on different conceptual influences to deal with a complex and challenging reality.

The generation and re-generation of social capital and enterprises in multi-stakeholders social cooperative enterprises: a system dynamic approach

Theories on social capital and on social entrepreneurship have mainly highlighted the attitude of social capital to generate enterprises and to foster good relations between third sector organizations and the public sector. This paper considers the social capital in a specific third sector enterprise; here, multi-stakeholder social cooperatives are seen, at the same time, as social capital results, creators and incubators. In the particular enterprises that identify themselves as community social enterprises, social capital, both as organizational and relational capital, is fundamental: SCEs arise from but also produce and disseminate social capital. This paper aims to improve the building of relational social capital and the refining of helpful relations drawn from other arenas, where they were created and from where they are sometimes transferred to other realities, where their role is carried on further (often working in non-profit, horizontally and vertically arranged groups, where they share resources and relations). To represent this perspective, we use a qualitative system dynamic approach in which social capital is measured using proxies. Cooperation of volunteers, customers, community leaders and third sector local organizations is fundamental to establish trust relations between public local authorities and cooperatives. These relations help the latter to maintain long-term contracts with local authorities as providers of social services and enable them to add innovation to their services, by developing experiences and management models and maintaining an interchange with civil servants regarding these matters. The long-term relations and the organizational relations linking SCEs and public organizations help to create and to renovate social capital. Thus, multi-stakeholder cooperatives originated via social capital developed in third sector organizations produce new social capital within the cooperatives themselves and between different cooperatives (entrepreneurial components of the third sector) and the public sector. In their entrepreneurial life, cooperatives have to contrast the "working drift," as a result of which only workers remain as members of the cooperative, while other stakeholders leave the organization. Those who are not workers in the cooperative are (stake)holders with "weak ties," who are nevertheless fundamental in making a worker's cooperative an authentic social multi-stakeholders cooperative. To maintain multi-stakeholder governance and the relations with third sector and civil society, social cooperatives have to reinforce participation and dialogue with civil society through ongoing efforts to include people that provide social proposals. We try to represent these processes in a system dynamic model applied to local cooperatives, measuring the social capital created by the social cooperative through proxies, such as number of volunteers and strong cooperation with public institutions. Using a reverse-engineering approach, we can individuate the determinants of the creation of social capital and thereby give support to governance that creates social capital.

Insuffisance rénale terminale d'origine lithiasique : fréquence, causes et prévention [Nephrolithiasis-induced ESRD: frequency, causes and prevention].

Nephrolithiasis still remains a too frequent - and under-appreciated - cause of end-stage renal disease (ESRD), and this is all the most unfortunate since such an untoward course is now preventable in most cases. Among 1391 patients who started maintenance dialysis at Necker hospital between 1989 and 2000, nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the 1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD in patients with infection and calcium nephrolithiasis. Based on our observations and on published reports, it emerges that most cases of nephrolithiasis-associated ESRD were due to sub-optimal management (especially in the case of infection or cystine stones) or to late (or erroneous) etiologic diagnosis, precluding early institution of appropriate therapeutic measures. In particular, several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were diagnosed while already on dialysis or after unsuccessful kidney transplantation, due to wrong initial diagnosis. In conclusion, thanks to recent advances in diagnosis and management of stone formers, ESRD should now be prevented in the great majority of patients, at the condition of early etiologic diagnosis based on accurate morphoconstitutional analysis of calculi and metabolic evaluation, and early implementation of appropriate preventive medical treatment.

Analysis of multi-scale systemic risk in Brazil's financial market

This work analyzes whether the relationship between risk and returns predicted by the Capital Asset Pricing Model (CAPM) is valid in the Brazilian stock market. The analysis is based on discrete wavelet decomposition on different time scales. This technique allows to analyze the relationship between different time horizons, since the short-term ones (2 to 4 days) up to the long-term ones (64 to 128 days). The results indicate that there is a negative or null relationship between systemic risk and returns for Brazil from 2004 to 2007. As the average excess return of a market portfolio in relation to a risk-free asset during that period was positive, it would be expected this relationship to be positive. That is, higher systematic risk should result in higher excess returns, which did not occur. Therefore, during that period, appropriate compensation for systemic risk was not observed in the Brazilian market. The scales that proved to be most significant to the risk-return relation were the first three, which corresponded to short-term time horizons. When treating differently, year-by-year, and consequently separating positive and negative premiums, some relevance is found, during some years, in the risk/return relation predicted by the CAPM. However, this pattern did not persist throughout the years. Therefore, there is not any evidence strong enough confirming that the asset pricing follows the model.

Multi-modal Change Detection, Application to the Detection of Flooded Areas: Outcome of the 2009-2010 data fusion contest

The 2009-2010 Data Fusion Contest organized by the Data Fusion Technical Committee of the IEEE Geoscience and Remote Sensing Society was focused on the detection of flooded areas using multi-temporal and multi-modal images. Both high spatial resolution optical and synthetic aperture radar data were provided. The goal was not only to identify the best algorithms (in terms of accuracy), but also to investigate the further improvement derived from decision fusion. This paper presents the four awarded algorithms and the conclusions of the contest, investigating both supervised and unsupervised methods and the use of multi-modal data for flood detection. Interestingly, a simple unsupervised change detection method provided similar accuracy as supervised approaches, and a digital elevation model-based predictive method yielded a comparable projected change detection map without using post-event data.