Rare Copy Number Variants in \u3cem\u3eNRXN1\u3c/em\u3e and \u3cem\u3eCNTN6\u3c/em\u3e Increase Risk for Tourette Syndrome

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (\u3c 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (\u3e 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10−3) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS

Los proyectos de inversión pública y su relación con el desarrollo de la actividad turística

The purpose was to understand to what extent the public investment projects carried out are related to the development of tourist activities in the Province of Huánuco - 2015. The method was quantitative, applied, deductive, non-experimental design - cross section, the sample was was made up of 167 PIPs from the study area. The following instruments were taken into account: record cards, electronic reference and observation. Statistical validation was done using Cronbach's alpha, with 96% reliability. Of the total number of PIPs carried out, according to the degree of evaluation of the influence of tourism development, there is a low and medium degree. Of all the projects, according to the evaluations of the degree of influence on the development of tourism, a medium and high degree was obtained. Of all the projects carried out by local governments, according to the evaluation of the degree of influence on the development of tourism, they have a medium and high degree. It is concluded that PIPs influence the growth of tourist activities.El propósito fue comprender en qué medida los Proyecto de Inversión Pública realizados se relacionan en el desarrollo de las actividades turísticas en la Provincia de Huánuco - 2015. El método fue cuantitativa, aplicada, deductiva, de diseño no experimental- corte transversal, la muestra se conformó por 167 PIP de la zona estudio. Se tuvo en cuenta los siguientes instrumentos: las fichas de registros, referencia electrónica y la observación. La validación estadística se dio mediante el alfa de Cronbach, con 96 % de confiabilidad. Del total de PIP realizados, según el grado de evaluación de influencia del desarrollo del turismo, se presenta un grado bajo y medio. Del total de proyectos, según las evaluaciones del grado de influencia en el desarrollo del turismo, se obtuvo un grado medio y alto. Del total de proyectos ejecutados por los gobiernos locales, según la evaluación del grado de influencia en el desarrollo del turismo, tienen un grado medio y alto. Se concluye que los PIP influyen en el crecimiento de las actividades turísticas

Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective evaluation

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety

Inclusive search for supersymmetry using razor variables in pp collisions at root s=13 TeV

Peer reviewe

Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci

Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity