Using open-access data to explore relations between urban landscapes and diarrhoeal diseases in Côte d'Ivoire

Unlike water and sanitation infrastructures or socio-economic indicators, landscape features are seldomly considered as predictors of diarrhoea. In contexts of rapid urbanisation and changes in the physical environment, urban planners and public health managers could benefit from a deeper understanding of the relationship between landscape patterns and health outcomes. We conducted an ecological analysis based on a large ensemble of open-access data to identify specific landscape features associated with diarrhoea. Designed as a proof-of-concept study, our research focused on Côte d'Ivoire. This analysis aimed to (i) build a framework strictly based on open-access data and open-source software to investigate diarrhoea risk factors originating from the physical environment and (ii) understand whether different types and forms of urban settlements are associated with different prevalence rates of diarrhoea. We advanced landscape patterns as variables of exposure and tested their association with the prevalence of diarrhoea among children under the age of five years through multiple regression models. A specific urban landscape pattern was significantly associated with diarrhoea. We conclude that, while the improvement of water, sanitation, and hygiene infrastructures is crucial to prevent diarrhoeal diseases, the health benefits of such improvements may be hampered if the overall physical environment remains precarious

Characteristic-time of strain induced crystallization of crosslinked natural rubber

International audienceReal time Wide-Angle X-ray Scattering (WAXS) measurements during cyclic tensile tests at high strain rates (from 8 s−1–280 s−1) and at room temperature on crosslinked Natural Rubber (NR) are performed thanks to a specific homemade device. From the observed influence of the frequency on the crystallization index at the maximum sample elongation, a characteristic crystallization time is deduced. This is done taking into account the material self-heating during such unusually high strain rates. Two regimes for the dynamic process of strain induced crystallization are evidenced. For the NR tested, the obtained characteristic time is around 20 ms when the material average elongation during the cyclic test is above a critical elongation value λc. λc is the minimum elongation needed to induce crystallization during low strain rate tensile tests. Moreover, a rapid increase of this characteristic time is found when the average elongation decreases below this critical value

Logarithmic asymptotics of the densities of SPDEs driven by spatially correlated noise

We consider the family of stochastic partial differential equations indexed by a parameter \eps\in(0,1], \begin{equation*} Lu^{\eps}(t,x) = \eps\sigma(u^\eps(t,x))\dot{F}(t,x)+b(u^\eps(t,x)), \end{equation*} (t,x)\in(0,T]\times\Rd with suitable initial conditions. In this equation, $L$ is a second-order partial differential operator with constant coefficients, $\sigma$ and $b$ are smooth functions and $\dot{F}$ is a Gaussian noise, white in time and with a stationary correlation in space. Let p^\eps_{t,x} denote the density of the law of u^\eps(t,x) at a fixed point (t,x)\in(0,T]\times\Rd. We study the existence of \lim_{\eps\downarrow 0} \eps^2\log p^\eps_{t,x}(y) for a fixed $y\in\R$. The results apply to a class of stochastic wave equations with $d\in\{1,2,3\}$ and to a class of stochastic heat equations with $d\ge1$.Comment: 39 pages. Will be published in the book " Stochastic Analysis and Applications 2014. A volume in honour of Terry Lyons". Springer Verla

Finsler geometry modeling of reverse piezoelectric effect in PVDF

We apply the Finsler geometry (FG) modeling technique to study the electric field-induced strain in ferroelectric polymers. Polyvinylidene difluoride (PVDF) has a negative longitudinal piezoelectric coefficient, which is unusual in ferroelectrics, and therefore the shape changes in this material are hard to predict. We find that the results of Monte Carlo simulations for the FG model are in good agreement with experimental strain-electric field curves of PVDF-based polymers in both longitudinal and transverse directions. This implies that FG modeling is suitable for reproducing the reverse piezoelectric effect in PVDF

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Modelling study of dimerization in mammalian defensins

BACKGROUND: Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. RESULTS: Based on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers. CONCLUSION: β-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits

Spontaneous virulence loss in natural populations of Listeria monocytogenes

International audienceThe pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene (hly) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes. Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA. Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA Ϫ /LLO Ϫ) mutants belonged to phylogenetically diverse clades of L. monocyto-genes, and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA Ϫ /LLO Ϫ muta-tional events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose