A comparison of the spatial dependence of body mass index among adults and children in a Swiss general population.

BACKGROUND: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether BMI clusters among children and how age-specific BMI clusters are related remains unknown. We aimed to identify and compare the spatial dependence of BMI in adults and children in a Swiss general population, taking into account the area's income level. METHODS: Geo-referenced data from the Bus Santé study (adults, n=6663) and Geneva School Health Service (children, n=3601) were used. We implemented global (Moran's I) and local (local indicators of spatial association (LISA)) indices of spatial autocorrelation to investigate the spatial dependence of BMI in adults (35-74 years) and children (6-7 years). Weight and height were measured using standardized procedures. Five spatial autocorrelation classes (LISA clusters) were defined including the high-high BMI class (high BMI participant's BMI value correlated with high BMI-neighbors' mean BMI values). The spatial distributions of clusters were compared between adults and children with and without adjustment for area's income level. RESULTS: In both adults and children, BMI was clearly not distributed at random across the State of Geneva. Both adults' and children's BMIs were associated with the mean BMI of their neighborhood. We found that the clusters of higher BMI in adults and children are located in close, yet different, areas of the state. Significant clusters of high versus low BMIs were clearly identified in both adults and children. Area's income level was associated with children's BMI clusters. CONCLUSIONS: BMI clusters show a specific spatial dependence in adults and children from the general population. Using a fine-scale spatial analytic approach, we identified life course-specific clusters that could guide tailored interventions.

The modal nature of structures in ontic structural realism

Ontic structural realism is the view that structures are what is real in the first place in the domain of fundamental physics. The structures are usually conceived as including a primitive modality. However, it has not been spelled out as yet what exactly that modality amounts to. This paper proposes to fill this lacuna by arguing that the fundamental physical structures possess a causal essence, being powers. Applying the debate about causal vs. categorical properties in analytic metaphysics to ontic structural realism, I show that the standard argument against categorical and for causal properties holds for structures as well. Structural realism, as a position in the metaphysics of science that is a form of scientific realism, is committed to causal structures. The metaphysics of causal structures is supported by physics, and it can provide for a complete and coherent view of the world that includes all domains of empirical science.

Association of different lipid measures for atherogenic lipid fractions and risk of coronary events in patients receiving combination antiretroviral therapy: the Swiss HIV Cohort Study

Background: Evidence for a better performance of different highly atherogenic versus traditional lipid parameters for coronary heart disease (CHD) risk prediction is conflicting. We investigated the association of the ratios of sma11 dense low density lipoprotein(LDL)/apoplipoprotein A, aolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol and CHD events in patients on combination antiretroviral therapy (cART).Methods: Case control study nested into the Swiss HIV Cohort Study: for each cART-treated patient with a first coronary event between April 1, 2000 and July 31, 2008 (case) we selected four control patients (1) that were without coronary events until the date of the event of the index case, (2) had a plasma sample within ±30 days of the sample date of the respective case, (3) received cART and (4) were then matched for age, gender and smoking status. Lipoproteins were measured by ultracentrifugation. Conditional logistic regression models were used to estimate the independent effects of different lipid ratios and the occurrence of coronary events.Results: In total, 98 cases (19 fatal myocardial infarctions [MI] and 79 non-fatal coronary events [53 definite MIs, 15 possible MIs and 11 coronary angioplasties or bypassesJ) were matched with 392 controls. Cases were more often injecting drug users, less likely to be virologically suppressed and more often on abacavir-containing regimens. In separa te multivariable models of total cholesterol, triglycerides, HDL-cholesterol, systolic blood pressure, abdominal obesity, diabetes and family history of CHD, small dense-LDL and apolipoprotein B were each statistically significantly associated with CHD events (for 1 mg/dl increase: odds ratio [OR] 1.05, 95% CI 1.00-1.11 and 1.15, 95% CI 1.01-1.31, respectively), but the ratiosof small dense-LDLlapolipoprotein A-I (OR 1.26, 95% CI 0.95-1.67), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and HDL-cholesterol! total cholesterol (OR 0.99 95% CI 0.98-1.00) were not. Following adjustment for HIV related and cART variables these associations were weakened in each model: apolipoprotein B (OR 1.27, 95% CI 1.00-1.30), sd-LDL (OR 1.04, 95% CI 0.99-1.20), small dense-LDLlapolipoprotein A-I (OR 1.17, 95% CI 0.87-1.58), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and total cholesterolJHDL- cholesterol (OR 0.99, 95% CI 0.99-1.00).Conclusions: In patients receiving cART, small dense-LDL and apolipoprotein B showed the strongest associations with CHD events in models controlling for traditional CHD risk factors including total cholesterol and triglycerides. Adding small dense LDLlapoplipoprotein A-l, apolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol ratios did not further improve models of lipid parameters and associations of increased risk for CHD events.

Evolutionary branching in deme-structured populations.

Adaptive dynamics shows that a continuous trait under frequency dependent selection may first converge to a singular point followed by spontaneous transition from a unimodal trait distribution into a bimodal one, which is called "evolutionary branching". Here, we study evolutionary branching in a deme-structured population by constructing a quantitative genetic model for the trait variance dynamics, which allows us to obtain an analytic condition for evolutionary branching. This is first shown to agree with previous conditions for branching expressed in terms of relatedness between interacting individuals within demes and obtained from mutant-resident systems. We then show this branching condition can be markedly simplified when the evolving trait affect fecundity and/or survival, as opposed to affecting population structure, which would occur in the case of the evolution of dispersal. As an application of our model, we evaluate the threshold migration rate below which evolutionary branching cannot occur in a pairwise interaction game. This agrees very well with the individual-based simulation results.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV-infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.

OBJECTIVES: HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy. METHODS: We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation. RESULTS: In models including cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events. CONCLUSIONS: HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression.

Literature review on advance care planning of nursing home residents

Aim: Conduct a search and analytic review of literature regarding attributes of Advance Care Planning (ACP) and Advance Directive in order to identify the experiences and the best care strategies for older adults resident in nursing homes or long term institutions. Methodology: An extensive electronic search was undertaken in the following databases: Pubmed (via Ovid search), Cumulative Index of Nursing and Allied Health (CINAHL, via EBHOST), psychINFO and Cochrane. After analyzing and eliminating duplicates and professional's point of view (19), 144 titles were considered relevant: 28 opinion papers, 94 descriptive/qualitative studies or predictive studies, 17 experimental and five systematic reviews. Most of them were produced in North America and only 10 were in French. Results: With regard to European experiences, studies are scarce and further research could benefit from North American evidence. Contrary to Europe, nurses in North America play a major role in the process of care planning. The major findings were related to the poor efficacy of the completion of Advance Directives, even in presence of a substantial variety of implementation strategies. The evidence supports interventions that conceptualize ACP as a process, with an emphasis on the ascertainment of patients' values and beliefs and the necessity to include the family or loved ones from the beginning of the process in order to favor the expression and sharing of one's life perspectives and priorities in care. The most relevant findings were associated with the conceptualization of the ACP as a change in health behaviors which needs an involvement in different stages to overcome a variety of barriers. Conclusion: Rigorous research in ACP for the older adults in Swiss nursing homes that promote respect and dignity in this frail population is needed. How to best achieve patients and families goals should be the focus of nursing intervention and research in this domain.

Ispol'zovanie metodov teorii vosstanovleniia v modeliakh optimal'nogo dobyvaniia pishchi [Restoration theory in models of optimal feeding behavior]

The method of stochastic dynamic programming is widely used in ecology of behavior, but has some imperfections because of use of temporal limits. The authors presented an alternative approach based on the methods of the theory of restoration. Suggested method uses cumulative energy reserves per time unit as a criterium, that leads to stationary cycles in the area of states. This approach allows to study the optimal feeding by analytic methods.

Essays on the measurement of school efficiency

Measuring school efficiency is a challenging task. First, a performance measurement technique has to be selected. Within Data Envelopment Analysis (DEA), one such technique, alternative models have been developed in order to deal with environmental variables. The majority of these models lead to diverging results. Second, the choice of input and output variables to be included in the efficiency analysis is often dictated by data availability. The choice of the variables remains an issue even when data is available. As a result, the choice of technique, model and variables is probably, and ultimately, a political judgement. Multi-criteria decision analysis methods can help the decision makers to select the most suitable model. The number of selection criteria should remain parsimonious and not be oriented towards the results of the models in order to avoid opportunistic behaviour. The selection criteria should also be backed by the literature or by an expert group. Once the most suitable model is identified, the principle of permanence of methods should be applied in order to avoid a change of practices over time. Within DEA, the two-stage model developed by Ray (1991) is the most convincing model which allows for an environmental adjustment. In this model, an efficiency analysis is conducted with DEA followed by an econometric analysis to explain the efficiency scores. An environmental variable of particular interest, tested in this thesis, consists of the fact that operations are held, for certain schools, on multiple sites. Results show that the fact of being located on more than one site has a negative influence on efficiency. A likely way to solve this negative influence would consist of improving the use of ICT in school management and teaching. Planning new schools should also consider the advantages of being located on a unique site, which allows reaching a critical size in terms of pupils and teachers. The fact that underprivileged pupils perform worse than privileged pupils has been public knowledge since Coleman et al. (1966). As a result, underprivileged pupils have a negative influence on school efficiency. This is confirmed by this thesis for the first time in Switzerland. Several countries have developed priority education policies in order to compensate for the negative impact of disadvantaged socioeconomic status on school performance. These policies have failed. As a result, other actions need to be taken. In order to define these actions, one has to identify the social-class differences which explain why disadvantaged children underperform. Childrearing and literary practices, health characteristics, housing stability and economic security influence pupil achievement. Rather than allocating more resources to schools, policymakers should therefore focus on related social policies. For instance, they could define pre-school, family, health, housing and benefits policies in order to improve the conditions for disadvantaged children.

A systematic review of longitudinal population-based studies on the predictors of smoking cessation in adolescent and young adult smokers.

OBJECTIVE: To describe the determinants of self-initiated smoking cessation of duration of at least 6 months as identified in longitudinal population-based studies of adolescent and young adult smokers. METHODS: A systematic search of the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop as keywords was performed. Limits included articles related to humans, in English, published between January 1984 and August 2010, and study population aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed independently by 2 and 3 reviewers, respectively. Nine articles were retained for data abstraction. Data on study location, timeframe, duration of follow-up, number of data collection points, sample size, age/grade of participants, number of quitters, smoking status at baseline, definition of cessation, covariates and analytic method were abstracted from each article. The number of studies that reported a statistically significant association between each determinant investigated and cessation were tabulated, from among all studies that assessed the determinant. RESULTS: Despite heterogeneity in methods across studies, five factors robustly predicted quitting across studies in which the factor was investigated: not having friends who smoke, not having intentions to smoke in the future, resisting peer pressure to smoke, being older at first use of cigarette and having negative beliefs about smoking. CONCLUSIONS: The literature on longitudinal predictors of cessation in adolescent and young adult smokers is not well developed. Cessation interventions for this population will remain less than optimally effective until there is a solid evidence base on which to develop interventions.

Using high-resolution quantitative mapping of R1 as an index of cortical myelination

A fundamental tenet of neuroscience is that cortical functional differentiation is related to the cross-areal differences in cyto-, receptor-, and myeloarchitectonics that are observed in ex-vivo preparations. An ongoing challenge is to create noninvasive magnetic resonance (MR) imaging techniques that offer sufficient resolution, tissue contrast, accuracy and precision to allow for characterization of cortical architecture over an entire living human brain. One exciting development is the advent of fast, high-resolution quantitative mapping of basic MR parameters that reflect cortical myeloarchitecture. Here, we outline some of the theoretical and technical advances underlying this technique, particularly in terms of measuring and correcting for transmit and receive radio frequency field inhomogeneities. We also discuss new directions in analytic techniques, including higher resolution reconstructions of the cortical surface. We then discuss two recent applications of this technique. The first compares individual and group myelin maps to functional retinotopic maps in the same individuals, demonstrating a close relationship between functionally and myeloarchitectonically defined areal boundaries (as well as revealing an interesting disparity in a highly studied visual area). The second combines tonotopic and myeloarchitectonic mapping to localize primary auditory areas in individual healthy adults, using a similar strategy as combined electrophysiological and post-mortem myeloarchitectonic studies in non-human primates.

A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on developing inhibitors of its tautomerase activity or modulating its biological activities using anti-MIF neutralizing antibodies. Herein we report a new class of isothiocyanate (ITC)-based irreversible inhibitors of MIF. Modification by benzyl isothiocyanate (BITC) and related analogues occurred at the N-terminal catalytic proline residue without any effect on the oligomerization state of MIF. Different alkyl and arylalkyl ITCs modified MIF with nearly the same efficiency as BITC. To elucidate the mechanism of action, we performed detailed biochemical, biophysical, and structural studies to determine the effect of BITC and its analogues on the conformational state, quaternary structure, catalytic activity, receptor binding, and biological activity of MIF. Light scattering, analytical ultracentrifugation, and NMR studies on unmodified and ITC-modified MIF demonstrated that modification of Pro1 alters the tertiary, but not the secondary or quaternary, structure of the trimer without affecting its thermodynamic stability. BITC induced drastic effects on the tertiary structure of MIF, in particular residues that cluster around Pro1 and constitute the tautomerase active site. These changes in tertiary structure and the loss of catalytic activity translated into a reduction in MIF receptor binding activity, MIF-mediated glucocorticoid overriding, and MIF-induced Akt phosphorylation. Together, these findings highlight the role of tertiary structure in modulating the biochemical and biological activities of MIF and present new opportunities for modulating MIF biological activities in vivo.

The C-terminal domain of Plasmodium falciparum merozoite surface protein 3 self-assembles into alpha-helical coiled coil tetramer.

Proteins located on the surface of the pathogenic malaria parasite Plasmodium falciparum are objects of intensive studies due to their important role in the invasion of human cells and the accessibility to host antibodies thus making these proteins attractive vaccine candidates. One of these proteins, merozoite surface protein 3 (MSP3) represents a leading component among vaccine candidates; however, little is known about its structure and function. Our biophysical studies suggest that the 40 residue C-terminal domain of MSP3 protein self-assembles into a four-stranded alpha-helical coiled coil structure where alpha-helices are packed "side-by-side". A bioinformatics analysis provides an extended list of known and putative proteins from different species of Plasmodium which have such MSP3-like C-terminal domains. This finding allowed us to extend some conclusions of our studies to a larger group of the malaria surface proteins. Possible structural and functional roles of these highly conserved oligomerization domains in the intact merozoite surface proteins are discussed.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

La politique régionale : entre compétitivité et respect de l'environnement

Aujourd'hui plus que jamais, le développement économique ne peut se faire au détriment de notre environnement naturel. Dès lors se pose la question de savoir comment parvenir à maintenir la compétitivité d'une économie, tout en tenant compte de l'impact qu'elle a sur révolution du cadre naturel. La présente recherche propose d'investiguer sur la question en se penchant sur les politiques publiques de promotion économique, et plus spécifiquement sur la politique régionale. Faut-il maintenir la confiance dans les courants néoclassiques, comme le laisse supposer la situation actuelle, renforcer la position d'une économie s'inscrivant au sein d'un cadre socio-environnemental ou encore repenser notre mode de fonctionnement économique quant à son développement ? Dans le cas présent, la politique régionale suisse est évaluée à la lumière de trois stratégies de développement économique. D'une part, il y a l'économie fondée sur la connaissance. Cette dernière est à la base de la philosophie actuelle en matière de politique régionale. Ensuite, il y a l'écologie industrielle, qui pour sa part fait la promesse d'un développement économique éco-compatible. Enfin, la troisième stratégie est celle de l'économie de fonctionnalité, qui propose de maximiser l'efficience d'une unité de matière première en limitant notamment la notion de propriété. Au travers d'une grille d'analyse construite sur le modèle des géographies de la grandeur, les trois stratégies sont confrontées aux objectifs de la nouvelle politique régionale suisse (NPR) ainsi qu'à ses modalités de mise en oeuvre. Il en ressort qu'en l'état actuel, la stratégie misant sur l'économie de la connaissance est la plus à même de relever le défi d'un développement économique durable. Toutefois, moyennant adaptations, les autres stratégies pourraient également se révéler être pertinentes. On constate notamment que les éléments clés sont ici l'innovation, ainsi que les dimensions spatiale et temporelle des stratégies. Nous recommandons dès lors d'adopter une approche territorialisée du développement économique, selon une logique de projet au sens de Boltanski & Chiapello. A notre sens, seules les propositions à même de fédérer les acteurs et disposant d'une vision intégrée du développement ont une chance de permettre un développement économique en harmonie avec notre cadre environnemental. - Today more than ever, economic development can't go ahead without consideration for our natural environment. This lays us with the question of how to maintain the competitiveness of an economy, and at the same time to manage the impact of it on the natural frame. This research aims to investigate this question through public policies fostering economy, more specifically through the regional policy. Must one trust the neo-classical way, as the actual situation let's think about it, reinforce the position of an economy within a socio- environmental frame or moreover reinvent our economical modus regarding development? In this case, an assessment of the Swiss regional policy is lead through three strategies of economic development. First, there is the knowledge economy. It is the core concept of the actual philosophy regarding regional policy. Second, there is the industrial ecology which aims to promote an eco-compatible economic development. Last, there is the functional economy, which proposes to maximize the efficiency of every used unit of natural resources by limiting in particular the notion of propriety. Through an analytic frame built on the model of geographies of greatness (géographies de la grandeuή, the three strategies are confronted to the objectives of the Swiss new regional policy (NRP) as well as its implementation. It turns out that actually, the strategy laying on the knowledge economy happens to be the best solution in order to promote a sustainable economic development. Nevertheless, with few adaptations, the other strategies could be pregnant as well. What we can see is that key- elements are here the innovation, as well as the spatial and temporal dimensions of these strategies. We recommend therefore to adopt a territorialised approach of economic development, with a project-based logic as meant by Boltanski & Chiapello. We are convinced that only propositions which are able to unit actors, and with an integrated point of view, have a chance to promote economic development in harmony with our environmental frame.