PABPN1 gene therapy for oculopharyngeal muscular dystrophy

International audienceOculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment

Using a community-based definition of poverty for targeting poor households for premium subsidies in the context of a community health insurance in Burkina Faso

Background: One of the biggest challenges in subsidizing premiums of poor households for community health insurance is the identification and selection of these households. Generally, poverty assessments in developing countries are based on monetary terms. The household is regarded as poor if its income or consumption is lower than a predefined poverty cut-off. These measures fail to recognize the multi-dimensional character of poverty, ignoring community members? perception and understanding of poverty, leaving them voiceless and powerless in the identification process. Realizing this, the steering committee of Nouna's health insurance devised a method to involve community members to better define `perceived? poverty, using this as a key element for the poor selection. The community-identified poor were then used to effectively target premium subsidies for the insurance scheme. Methods: The study was conducted in the Nouna's Health District located in northwest Burkina Faso. Participants in each village were selected to take part in focus-group discussions (FGD) organized in 41 villages and 7 sectors of Nouna's town to discuss criteria and perceptions of poverty. The discussions were audio recorded, transcribed and analyzed in French using the software NVivo 9. Results: From the FGD on poverty and the subjective definitions and perceptions of the community members, we found that poverty was mainly seen as scarcity of basic needs, vulnerability, deprivation of capacities, powerlessness, voicelessness, indecent living conditions, and absence of social capital and community networks for support in times of need. Criteria and poverty groups as described by community members can be used to identify poor who can then be targeted for subsidies. Conclusion: Policies targeting the poorest require the establishment of effective selection strategies. These policies are well-conditioned by proper identification of the poor people. Community perceptions and criteria of poverty are grounded in reality, to better appreciate the issue. It is crucial to take these perceptions into account in undertaking community development actions which target the poor. For most community-based health insurance schemes with limited financial resources, using a community-based definition of poverty in the targeting of the poorest might be a less costly alternative

ICAR: endoscopic skull‐base surgery

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High-resolution bulk density images, using calibrated X-ray radiography of impregnated soil slices

Bulk density of undisturbed soil samples can be measured using computed tomography (CT) techniques with a spatial resolution of about 1 mm. However, this technique may not be readily accessible. On the other hand, x-ray radiographs have only been considered as qualitative images to describe morphological features. A calibration procedure was set up to generate two-dimensional, high-resolution bulk density images from x-ray radiographs made with a conventional x-ray diffraction apparatus. Test bricks were made to assess the accuracy of the method. Slices of impregnated soil samples were made using hardsetting seedbeds that had been gamma scanned at 5-mm depth increments in a previous study. The calibration procedure involved three stages: (i) calibration of the image grey levels in terms of glass thickness using a staircase made from glass cover slips, (ii) measurement of ratio between the soil and resin mass attenuation coefficients and the glass mass attenuation coefficient, using compacted bricks of known thickness and bulk density, and (iii) image correction accounting for the heterogeneity of the irradiation field. The procedure was simple, rapid, and the equipment was easily accessible. The accuracy of the bulk density determination was good (mean relative error 0.015), The bulk density images showed a good spatial resolution, so that many structural details could be observed. The depth functions were consistent with both the global shrinkage and the gamma probe data previously obtained. The suggested method would be easily applied to the new fuzzy set approach of soil structure, which requires generation of bulk density images. Also, it would be an invaluable tool for studies requiring high-resolution bulk density measurement, such as studies on soil surface crusts

Practical Fully Secure Unrestricted Inner Product Functional Encryption modulo p

Functional encryption is a modern public-key cryptographic primitive allowing an encryptor to finely control the information revealed to recipients from a given ciphertext. Abdalla, Bourse, De Caro, and Pointcheval (PKC 2015) were the first to consider functional encryption restricted to the class of linear functions, i.e. inner products. Though their schemes are only secure in the selective model, Agrawal, Libert, and Stehlé (CRYPTO 16) soon provided adaptively secure schemes for the same functionality. These constructions, which rely on standard assumptions such as the Decision Diffie-Hellman (DDH), the Learning-with-Errors (LWE), and Paillier's Decision Composite Residuosity (DCR) problems, do however suffer of various practical drawbacks. Namely, the DCR based scheme only computes inner products modulo an RSA integer which is oversized for many practical applications, while the computation of inner products modulo a prime p either requires, for their (DDH) based scheme, that the inner product be contained in a sufficiently small interval for decryption to be efficient, or, as in the LWE based scheme, suffers of poor efficiency due to impractical parameters. In this paper, we provide adaptively secure functional encryption schemes for the inner product functionality which are both efficient and allow for the evaluation of unbounded inner products modulo a prime p. Our constructions rely on new natural cryptographic assumptions in a cyclic group containing a subgroup where the discrete logarithm (DL) problem is easy which extend Castagnos and Laguillaumie's assumption (RSA 2015) of a DDH group with an easy DL subgroup. Instantiating our generic construction using class groups of imaginary quadratic fields gives rise to the most efficient functional encryption for inner products modulo an arbitrary large prime p. One of our schemes outperforms the DCR variant of Agrawal et al.'s protocols in terms of size of keys and cipher-texts by factors varying between 2 and 20 for a 112-bit security.AppLicAtions de la MalléaBIlité en CryptographieLattices: algorithms and cryptograph

Anthropometric relationships between parents and children throughout childhood: the Fleurbaix-Laventie Ville Santé Study.

BACKGROUND: The study of parent-child anthropometric relationships and their evolution over time may help to better understand familial risk factors for childhood obesity. METHODS: In a population-based cohort of 124 nuclear families (Fleurbaix-Laventie Ville Sant?tudy (FLVS) I and II), various anthropometric parameters were measured in both parents and their children, first when the children were prepubescent and again at the end of puberty. Troncular adiposity repartition was estimated by calculating troncular to peripheral skinfolds ratio and waist-to-hip circumferences ratio. Birth and infancy heights and weights were also obtained from the children's health booklets. Parent-child correlations were estimated in infancy, before and at the end of the child's puberty. A prospective analysis was performed to predict the changes in the children's measurements over puberty according to their parents' corresponding baseline values. RESULTS: BMI and weight correlations at birth were high (>0.30) with the mother and low (<0.10) with the father, then they converged to an intermediate level at 2 y and remained between 0.2 and 0.3 thereafter. Correlations for waist circumference were already present at the prepubertal period and persisted on the same level at the postpubertal period, whereas correlations for subcutaneous adiposity - measured by four skinfolds - and for adiposity distribution - measured by ratios - were higher at the postpubertal period. Moreover, the prospective approach showed that mother's BMI predicted the evolution of her children's BMI over puberty, whereas this relationship was observed more specifically with the father concerning adiposity distribution parameters. CONCLUSION: Maternal adiposity may act early in life on the adiposity of the child. Maternal and paternal adiposities seem to have quite distinct effects at two key periods of the child's adiposity development such as the prenatal and pubertal periods