208 research outputs found

    Precision global health in the digital age.

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    Precision global health is an approach similar to precision medicine, which facilitates, through innovation and technology, better targeting of public health interventions on a global scale, for the purpose of maximising their effectiveness and relevance. Illustrative examples include: the use of remote sensing data to fight vector-borne diseases; large databases of genomic sequences of foodborne pathogens helping to identify origins of outbreaks; social networks and internet search engines for tracking communicable diseases; cell phone data in humanitarian actions; drones to deliver healthcare services in remote and secluded areas. Open science and data sharing platforms are proposed for fostering international research programmes under fair, ethical and respectful conditions. Innovative education, such as massive open online courses or serious games, can promote wider access to training in public health and improving health literacy. The world is moving towards learning healthcare systems. Professionals are equipped with data collection and decision support devices. They share information, which are complemented by external sources, and analysed in real time using machine learning techniques. They allow for the early detection of anomalies, and eventually guide appropriate public health interventions. This article shows how information-driven approaches, enabled by digital technologies, can help improving global health with greater equity

    Estimation du caractère impulsionnel du bruit dans une image non stationnaire

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    Nous proposons dans cet article un nouvel opérateur pour mesurer le caractère impulsionnel du bruit d'image. L'objectif est d'obtenir un opérateur robuste vis-à-vis des non stationnarités de l'image. Cet opérateur est invariant par translation et facteur d'échelle. Il permet d'estimer le caractère impulsionnel du bruit dans une région de taille relativement faible

    Estimating and predicting snakebite risk in the Terai region of Nepal through a high-resolution geospatial and One Health approach

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    Most efforts to understand snakebite burden in Nepal have been localized to relatively small areas and focused on humans through epidemiological studies. We present the outcomes of a geospatial analysis of the factors influencing snakebite risk in humans and animals, based on both a national-scale multi-cluster random survey and, environmental, climatic, and socio-economic gridded data for the Terai region of Nepal. The resulting Integrated Nested Laplace Approximation models highlight the importance of poverty as a fundamental risk-increasing factor, augmenting the snakebite odds in humans by 63.9 times. For animals, the minimum temperature of the coldest month was the most influential covariate, increasing the snakebite odds 23.4 times. Several risk hotspots were identified along the Terai, helping to visualize at multiple administrative levels the estimated population numbers exposed to different probability risk thresholds in 1 year. These analyses and findings could be replicable in other countries and for other diseases

    Improved methods for detection of β-galactosidase (lacZ) activity in hard tissue

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    The ß-galactosidase gene (lacZ) of Escherichia coli is widely used as a reporter gene. The expression of lacZ can be detected by enzyme-based histochemical staining using chromogenic substrates such as 5-bromo-4-chloro-3-indolyl-ß-D: -galactoside (X-gal). Because the enzymatic activity of lacZ is vulnerable to high temperatures and acid treatment for demineralization, detection of lacZ on paraffinized sections is difficult, especially for hard tissues, which require demineralization before sectioning in paraffin. To circumvent this problem, whole-mount X-gal staining before sectioning is performed. However, detection of lacZ activity in the center of larger portions of hard whole adult tissues is challenging. In this study, focusing on fixation procedures, we determined the conditions conducive to improved detection of lacZ activity in deeper areas of whole tissues. We used an annexin a5 (Anxa5)-lacZ reporter mouse model in which the Anxa5 expression in hard tissue is indicated by lacZ activity. We found that lacZ activity could be detected throughout the periodontal ligament of adult mice when fixed in 100% acetone, whereas it was not detected in the periodontal ligament around the root apex fixed in glutaraldehyde and paraformaldehyde. This staining could not be detected in wild-type mice. Acetone maintains the lacZ activity within 48 h of fixation at both 4°C and at room temperature. In conclusion, acetone is the optimal fixative to improve permeability for staining of lacZ activity in large volumes of adult hard tissues

    A Measure of the Promiscuity of Proteins and Characteristics of Residues in the Vicinity of the Catalytic Site That Regulate Promiscuity

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    Promiscuity, the basis for the evolution of new functions through ‘tinkering’ of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE) - based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (μ = 0.28, σ = 1.1 reduced chi-square = 3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R2∼0.1) between certain properties of the residues (charge, polar, etc) in the neighborhood of the catalytic residues and PromIndex. A stronger relationship states that most proteins with high promiscuity have high percentages of charged and polar residues within a radius of 3 Å of the catalytic site, which is validated using one-tailed hypothesis tests (P-values∼0.05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE

    Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

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