Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Residential Composting as an instrument of environmental education and reduction of solid wastes. Campos do Jordão, São Paolo.

No Brasil, a parcela orgânica dos resíduos sólidos urbanos (RSU) representa mais de 50% de sua composição, na grande maioria dos municípios. No entanto, a compostagem, como método de tratamento dos resíduos orgânicos, não é empregada como poderia, somente 1,5% dos RSU no país é compostados; mesmo a compostagem caseira sendo prática de baixo custo e apropriada a áreas residenciais não é usual. O presente trabalho enfatiza a educação ambiental (EA) como instrumento para a organização e participação social, visando à minimização de resíduos sólidos urbanos, através da implantação de composteiras caseiras. O enfoque é dado no envio dos resíduos orgânicos domiciliares para compostagem caseira e na incorporação de novos hábitos, após execução de programa de educação ambiental em uma comunidade, do município de Campos do Jordão, São Paulo, Brasil. No presente estudo, partiu-se das seguintes hipóteses; comunidades de baixos ingressos e pouca instrução, localizadas em bairros periféricos de centros urbanos, são capazes de se organizar e alterar seu comportamento com relação à questão da geração e descarte de RSU, quando convidados a integrar grupos submetidos a programa de Educação Ambiental, com metodologia participativa; aliando-se atividades teóricas e práticas elaborado de acordo com as necessidades específicas da comunidade e implantados considerando-se a realidade local. Os resultados alcançados foram a organização social da comunidade, com o desvio de 83,5% dos resíduos orgânicos do aterro para a compostagem, isso quando não foram minimizados antes, no aproveitamento completo dos alimentos. A prática da compostagem possibilitou testar vários tipos de composteira caseira e garantiu melhorias nas condições de disposição dos RSU, reduzindo os impactos ambientais.In Brazil, the organic portion of the solid wastes represents more than 50% of its composition in most of the cities. However, the composting , as a method of organic wastes treatment, is not applied as it could be, only 1.5% of the Urban Solid Waste (USW or in Portuguese, RSU) is recycled; even the home composting, which has a low cost and is appropriated in residential areas, is not common. This current paper emphasizes the environmental education as an instrument for the social organization and participation as well as minimization of solid wastes, which are essential elements for a sustainable development. The approach is based on the reduction of solid wastes by sending the home organic waste to home composting and the incorporation of new habits after the execution of an environmental education program in a community from the city of Campos do Jordão (São Paulo - Brazil). The research was originated on the hypothesis that communities with lack of basic facilities and lower education rates located in surrounding areas of urban centers are capable of organizing and changing its habits in relation to production and discarding of USW. This is possible especially when people are invited to integrate groups committed to an environmental education program according to the specific needs of the community and considering the local reality. The obtained results were the social organization of the community, with the allocation of 83,5% of the organic wastes from landfills to composting, that is when it was not minimized before, with the complete use of food. The composting made it to possible to test various types of home composting and assured improvements in the disposal conditions of the USW, reducing environmental impact

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Measurement of the polarization of the Xi0 (anti-Xi0) hyperon beam by the NA48/1 experiment

A total of 368415 Xi(0) --> Lambda Xi(0) and 31 171 (Xi(0)) over bar --> (Lambda) over bar pi(0) were selected from data recorded in the NA48/1 experiment during 2002 data taking. From this sample, the polarization of Xi(0) and (Xi(0)) over bar hyperons was measured to be P(Xi 0) = -0.102 +/- 0.012(stat) +/- 0.008(syst) and P((Xi 0) over bar) = -0.01 +/- 0.04(stat) 0.008(syst). The dependence of P(Xi 0) on the Xi(0) transverse momentum with respect to the primary proton beam is also presented. With the same data sample. the ratio of (Xi(0)) over bar and Xi(0) fluxes in proton collisions at 400 GeV/c oil a beryllium target was measure

Search for heavy neutrinos in K+→μ+νμK^+ \rightarrow \mu^+ \nu_{\mu} decays

International audienceThe NA62 experiment recorded a large sample of K+→μ+νμ decays in 2007. A peak search has been performed in the reconstructed missing mass spectrum. In the absence of a signal, limits in the range 2×10−6 to 10−5 have been set on the squared mixing matrix element |Uμ4|2 between muon and heavy neutrino states, for heavy neutrino masses in the range 300–375 MeV/ c2 . The result extends the range of masses for which upper limits have been set on the value of |Uμ4|2 in previous production search experiments

Determination of the relative decay rate KS -> πeν / KL -> πeν

The decay rate of K-S -> pi ev relative to the rate of K-L -> pi rev has been measured by the NA48 Collaboration in a neutral kaon beam originating from 400 GeV proton-Be interactions at the CERN SPS. The result is 0.993 +/- 0.026(stat) +/- 0.022(syst), compatible with I in agreement with the Standard Model prediction at tree level. It implies B R (K-S -> pi ev) = (7.05 +/- 0.18(stat) +/- 0.16(syst)) X 10(-4)

Oncoplastic and reconstructive surgery in SENONETWORK Italian breast centers: lights and shadows

: • Despite the significance of oncoplastic procedure, an italian database is lacking. • Senonetwork established a multidisciplinary survey to assess their safety and efficacy. • Reconstructive outcomes were positive across low and high-volume centers. • After mastectomy, implant-based techniques are common. DTI reconstruction is advantageuos. • This contributes to the global understanding of effective strategies against breast cancer

Measurement of the form factors of charged kaon semileptonic decays

International audienceA measurement of the form factors of charged kaon semileptonic decays is presented, based on 4.4 × 10$^{6}$K$^{±}$ → π$^{0}$e$^{±}$ν$_{e}$ (K$_{e3}^{±}$ ) and 2.3 × 10$^{6}$K$^{±}$ → π$^{0}$μ±ν$_{μ}$ (K$_{μ3}^{±}$ ) decays collected in 2004 by the NA48/2 experiment. The results are obtained with improved precision as compared to earlier measurements. The combination of measurements in the K$_{e3}^{±}$ and K$_{μ3}^{±}$ modes is also presented

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

The NA48/2 experiment at CERN reports the first observation of the $K^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu$ decay based on a sample of 2437 candidates with 15% background contamination collected in 2003-2004. The decay branching ratio in the kinematic region of the squared dilepton mass above $0.03$~GeV$^2/c^4$ is measured to be $(0.65 \pm 0.03) \times 10^{-6}$. The extrapolation to the full kinematic space, using a specific model, is found to be $(3.45 \pm 0.17) \times 10^{-6}$, in agreement with chiral perturbation theory predictions

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

International audienceThe NA48/2 experiment at CERN reports the first observation of the K$^{±}$ → π$^{0}$π$^{0}$μ$^{±}$ν decay based on a sample of 2437 candidates with 15% background contamination collected in 2003–2004. The decay branching ratio in the kinematic region of the squared dilepton mass above 0.03 GeV$^{2}$/c$^{4}$ is measured to be (0.65 ± 0.03) × 10$^{−6}$. The extrapolation to the full kinematic space, using a specific model, is found to be (3.45 ± 0.16) × 10$^{−6}$, in agreement with chiral perturbation theory predictions