Lactobacillus acidophilus versus placebo in the symptomatic treatment of irritable bowel syndrome: the LAPIBSS randomized trial.

Irritable bowel syndrome is a chronic functional gastrointestinal disorder characterized by abdominal pain/discomfort and altered bowel habits. The use of Lactobacilli as probiotics during irritable bowel syndrome is based on their interesting mechanisms of action and their excellent safety profile but little is known about their clinical efficacy due to the lack of adequately designed clinical trials. The current clinical trial protocol aims to determine the effects of a mixture of Lactobacillus acidophilus NCFM and LAFTI L10 as probiotics to improve irritable bowel syndrome symptoms (LAPIBSS). Eighty patients with a positive diagnosis of irritable bowel syndrome according to Rome III criteria were recruited to a multicentre, double-blinded, in parallel groups, placebo-controlled randomized trial. Patients were provided with a daily dose of two capsules with two strains of Lactobacilli (5x109cfu/capsule) or placebo for 8 weeks on a 1:1 ratio. The primary outcome is to obtain scores of abdominal pain/discomfort assessed with a 100-mm visual analogue scale. The secondary outcome is to obtain scores of bloating, flatus and rumbling tested with a 100-mm visual analogue scale, composite score, stool frequency and stool consistency/appearance assessed with the Bristol Stool Form scale. According to the hypothesis that abdominal pain is mainly the result of a visceral hypersensitivity, the current study protocol aims to provide high quality proof of concept data to elucidate the efficacy of a consumption of a mixture of Lactobacillus acidophilus probiotic strains after 8 weeks, for decreasing abdominal pain. Ethical approval was given by ethics committee French Consultative Committee for the Protection of Individuals in Biomedical Research of the South West (Number CPP08-014a) and ANSM (French National Agency for Medicines and Health Products Safety - Number B80623-40). The findings from LAPBISS will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION: EudraCT N°2008-A00844-51.

Quantum interference and decoherence in single-molecule junctions: how vibrations induce electrical current.

Quantum interference and decoherence in single-molecule junctions is analyzed employing a nonequilibrium Green's function approach. Electrons tunneling through quasidegenerate states of a molecular junction exhibit interference effects. We show that electronic-vibrational coupling, inherent to any molecular junction, strongly quenches such interference effects. This decoherence mechanism may cause significantly larger electrical currents and is particularly pronounced if the junction is vibrationally highly excited, e.g., due to inelastic processes in the resonant transport regime.

Genomic studies in AIDS: problems and answers. Development of a statistical model integrating both longitudinal cohort studies and transversal observations of extreme cases.

Genomic studies developed to understand HIV-1 infection and pathogenesis have often lead to conflicting results. This is linked to various factors, including differences in cohort design and selection, the numbers of patients involved, the influence of population substructure, the ethnic origins of the participants, and phenotypic definition. These difficulties in the interpretation of results are examined through published studies on the role of polymorphisms in HLA and the chemokine receptors genes in AIDS. Our analysis suggests that the use of haplotypes will strengthen the results obtained in a given cohort, and meta-analysis including multiple cohorts to gather large-enough numbers of patients should also allow clarification of the genetic associations observed. A P-value of 0.001 appears to be a good compromise for significance on candidate genes in a genetic study. Due to the generally limited size of available cohorts, results will have to be validated in other cohorts. We developed a model to fit transversal case studies (extreme case-control studies) with longitudinal cohorts (all-stages patients) for observations on two gene polymorphisms of CCR5 and NQO1. Interestingly, we observe a protective effect for the CCR5-Delta32 mutant allele in 95% of the simulations based on that model when using a population of 600 subjects; however, when using populations of 250 subjects we find a significant protection in only 59% of the simulations. Our model gives thus an explanation for the discrepancies observed in the various genomic studies published in AIDS on CCR5-Delta32 and other gene polymorphisms: they result from statistical fluctuations due to a lack of power. The sizes of most seroconverter cohorts presently available seem thus insufficient since they include less than a few hundred subjects. This result underlines the power and usefulness of the transversal studies involving extreme patients and their complementarity to longitudinal studies involving seroconverter cohorts. The transposition approach of extreme case-control data into longitudinal analysis should prove useful not only in AIDS but also in other diseases induced by chronic exposure to a foreign agent or with chronic clinical manifestations.

An individual modelling tool for consecutive clinical mastitis during the same lactation in dairy cows: a method based on a survival model.

The high number of clinical mastitis recurring within the same lactation in dairy cows constitutes one of the factors of overdispersion in standard Poisson models. Our method, based on biological parameters, i.e., recurrence hazard in relation to udder exogenous infection (Rex) or recurrence hazard and rate in relation to endogenous infection (Ren), produced a model capable of integrating a possible change of state in the udder after clinical mastitis. This model was based on a study of the time intervals between successive clinical episodes, both types of risk being considered in the form of a distribution mixture in the survival model. The modelling tool allowed to determine the factors that specifically act on either one of the potential risks and estimated the distribution of the number of clinical mastitis per lactation, as well as the distribution of when mastitis occurs. Estimation results obtained by this method in an experimental herd were compared with those from more classical models with or without random individual effects. The distribution of the number of mastitis per lactation estimated by our method was well-fitted to the data and the method identified variation factors which were relatively standard in this type of study: lactation number, lactation stage and calving month. Prediction results obtained in another experimental herd with more recent data without parameter re-estimation demonstrated the adequacy of the model in fitting observed data. This modelling method based on biological parameters in a mixture of survival distributions was interesting to model clinical mastitis recurring within the same lactation. However in the future it will also be important to integrate the possible relationship between successive lactations and to apply this model to other types of farming systems.

Terminal cancer. duration and prediction of survival time.

The duration of the terminal period of cancer allows us to determine its prevalence, which is necessary to plan palliative care services. Clinical prediction of survival influences access to palliative care and the healthcare approach to be adopted. The objective of this study was to determine the duration of the terminal period, the prognostic ability of healthcare professionals to predict this terminal period and the factors that can improve the prognostic accuracy. In the island of Mallorca, Spain, we followed 200 cancer patients at the inception of the terminal period. Twenty-one symptoms, quality of life, prognosis and duration of survival were measured. Using a Cox regression model, a predictive survival model was built. Median duration was 59 days; 95% confidence interval (CI)=49-69 days, mean=99 days. The oncologists were accurate in their predictions (+/-1/3 duration) in 25.7% of cases, the nurses in 21.5% of cases and the family physicians in 21.7% of cases. Errors of overestimation occurred 2.86-4.14 times more frequently than underestimation. In the final model, in addition to clinical prognosis (P=0.0094), asthenia (P=0.0257) and the Hebrew Rehabilitation Centre for Aged Quality of Life (HRCA-QL) Index (P=0.0002) were shown to be independent predictors of survival. In this study, the estimated duration of the terminal period was greater than that reported in a series of palliative care programmes, and survival was overestimated. Oncologists could estimate prognosis more accurately if they also take into account asthenia and HRCA-QL Index.

[Knowledge, beliefs and attitudes of the female population towards cancer in Mallorca]. / Conocimientos, creencias y actitudes de la población femenina de Mallorca respecto al cáncer.

BACKGROUND: To analyze the knowledge of the facts on the part of the female population of Mallorca with regard to the causes of cancer, the beliefs regarding diagnosis and treatment and their attitude toward prevention. METHODS: A descriptive cross-section study of a random population sample (n = 124) of women within the 40-69 age range. The questionnaire includes socio-demographic variables, risk factors, early warning symptoms and beliefs regarding diagnosis and treatment and attitudes toward prevention. RESULTS: Cigarette smoking (92.7%; CI:88.1-97.3) and drinking alcoholic (85.7%; CI:79.4-92.0) are the most well-identified causes. Also the presence of a lump in the breast (92.6%; CI:87.9-97.2) and changes in a mole or wart on the skin (89.7%; CI:84.2-95.2%). The underestimate the role of the diet (44.4%; CI:35.1-53.8) and overestimate the environmental factors. The knowledge and use of self-examination procedures on the breast are associated directly with the degree of education (p < 0.05). Most believe that early diagnosis improves the prognosis (IC:94.2-99.5) and that treatment is beneficial (85.2%; CI:78.5-91.9). They consider surgery to be the most highly effective method, and in the event of any doubt they would first see their primary care physician (41.9%; CI:33.2-50.6). It is mainly older women having a low level of completed schooling who get their information regarding cancer above all from the television (43.5%; CI:34.8-52.3). Worthy of special mention is the very small impact of health care personal as a source of information (6.5%; CI:2.1-10.8). CONCLUSIONS: A major knowledge of the facts exists regarding the causes and warning signs, although some misconceptions do exist. In view of future prevention campaigns, educational measures addressed mainly to older women having a low level of completed schooling should be carried out.

[Estimating the costs of health care for patients infected with the human immunodeficiency virus in a university hospital in Catalonia]. / Estimación de los costes de la asistencia sanitaria a los pacientes infectados por el virus de la inmunodeficiencia humana en un hospital universitario de Cataluña.

BACKGROUND: To estimate the use of resources and costs of health care to patients infected with the human immunodeficiency virus (HIV). METHODS: Prospective study in university hospital in Catalonia including 166 patients. AIDS was defined following 1987 criteria of the Centers for Disease Control. AIDS phase was divided into three grades according to the evolutive course: AIDS grade I, II and III. Resources/costs were calculated in function of the degree of disease, transmission mode and demographic variants. RESULTS: The mean cost per patient/year (PY) was 1,571,900 pesetas, ranging from 88,700 for the asymptomatic phase and 2,561,000 per AIDS phase. Within the AIDS phase costs ranged from 1,593,317 for AIDS grade I to 4,903,183 for grade III. This increase was due to differences in hospitalization days for PY (up to 12.4 days in pre-AIDS phases, 45.8 for AIDS phase I and 119.4 for AIDS phase III) and days in day-hospital per PY (38.1 days for AIDS grade III). Parenteral drug abusers (PDA) had a PY cost 42% lower than that corresponding to sexually infected patients. CONCLUSIONS: Health care costs per PY of HIV infected patients increase with disease progression, which relates to the increase in hospitalization days and day-hospital hospitalization that occurs in the advanced phases of the disease. Our results suggest that health care to PDA is cheaper than that for sexually infected patients.

Measuring and testing genetic differentiation with ordered versus unordered alleles.

Estimates and variances of diversity and differentiation measures in subdivided populations are proposed that can be applied to haplotypes (ordered alleles such as DNA sequences, which may contain a record of their own histories). Hence, two measures of differentiation can be compared for a single data set: one (GST) that makes use only of the allelic frequencies and the other (NST) for which similarities between the haplotypes are taken into account in addition. Tests are proposed to compare NST and GST with zero and with each other. The difference between NST and GST can be caused by several factors, including sampling artefacts, unequal effect of mutation rates and phylogeographic structure. The method presented is applied to a published data set where a nuclear DNA sequence had been determined from individuals of a grasshopper distributed in 24 regions of Europe. Additional insights into the genetic subdivision of these populations are obtained by progressively combining related haplotypes and reanalyzing the data each time.

Tests for genetic linkage and homogeneity.

This report concerns likelihood ratio tests in a heterogeneous model for linkage, where the recombination fraction has a binomial mixture distribution with an unknown proportion of unlinked families. We consider families of unequal sizes with known or unknown phase data. In both cases, the limit distributions of the linkage test statistics are a mixture of a mass at ) and of a X2/1 distribution in equal proportions and homogeneity test statistics tend to the supremum of Gaussian processes. The critical values of the homogeneity tests are simulated, and the power functions of the linkage and homogeneity tests are compared in a simulation study.

Estimation, variance and optimal sampling of gene diversity II. Diploid locus.

Nei's analysis of diversity at a diploid locus is extended to a population subdivided into a large number of subpopulations. The diversities and the heterozygotes frequency are defined with respect to the total population and unbiasedly estimated in a two-stage random cluster sampling. The fixation indices F IS, F IT andF ST are derived, then inter- and intra-population variances of the estimated parameters are studied. We show that there is a unique sample size per population which yields the best accuracy in estimatingF ST and F IS, respectively, at a given locus. These results are illustrated with an analysis of DNA diversity in a forest tree and compared to those obtained under the Hardy-Weinberg assumption.

Estimation, variance and optimal sampling of gene diversity : I. Haploid locus.

An extension of Nei's analysis of diversity in a subdivided population is proposed for a haploid locus. The differentiation G STbecomes a natural extension of Wright's F STand generalizes Weir and Cockerham's parameter of co-ancestry by relaxing the assumption of identical correlation for all the alleles. Inter- and intrapopulation variances of the estimated diversities and differentiation are derived. Finally, the optimal sampling strategy for measuring G STwhen a fixed number of individuals can be analysed is considered. It is shown that, at a given locus, there is a unique sample size per population which yields the smallest variance of G ST,regardless of the number of populations studied. These theoretical developments are illustrated with an analysis of chloroplast DNA diversity in a forest tree. The results emphasize the necessity of sampling many populations, rather than many individuals per population, for an accurate measurement of the subdivision of gene diversity at a single locus.