Percutaneous management of acute necrotizing pancreatitis

OBJECTIVES: The study aims to evaluate the efficacy of percutaneous necrosectomy (PN) performed under ultrasound control and of endoscopic necrosectomy through secondary sinus track (ENTSST) using nephroscope and cystoscope.MATERIAL AND METHOD: Puncture of fluid collections in the pancreas was performed under ultrasonographic control to 23 patients with acute necrotizing pancreatitis (ANP). ENTSST using nephroscope and cystoscope was performed to 47 patients after open or percutaneous necrosectomy and persistent sepsis (without satellite collection of CT).RESULTS: Seventeen patients (74%) treated with percutaneous necrosectomy recovered without open surgery. Two of this group died. The average hospital stay was 42 days. Twenty-three patients required an average of two (range 1-4) ENTSST.CONCLUSIONS: Based on our initial results we believe that the percutaneous necrosectomy and ENTSST in well selected patients might be the better choice than open necrosectomy and postoperative lavage. Common solution for these methods has not been reached yet

Twofold efficiency increase in nanocrystalline-TiO2/polymer photovoltaic devices by interfacial modification with a lithium salt

Modification of the interface of titanium dioxide/poly[2-(2-ethylhexyloxy)-5-methoxy-1,4,-phenylenevinylene] (TiO2/MEH-PPV) nanocomposite photovoltaic devices with a lithium salt, Li[CF3SO2](2)N, is shown to result in a twofold increase in device efficiency. The devices are of the type ITO/TiO2/MEH-PPV/Au. The TiO2 layer is deposited by doctor blading a colloidal anatase paste, and the polymer is then spin-coated on top followed by thermal evaporation of gold contacts. Careful control of manufacturing conditions and use of a 35 nm polymer layer leads to a device efficiency of 0.48% for un-modified devices. The increased efficiency following Li treatment is the result of a 40% increase in both the short-circuit current and fill factor, while the open-circuit voltage remains unchanged. A maximum efficiency of 1.05% has been achieved under 80% sun illumination. This represents a record efficiency for this type of cell. Photoconductivity experiments show a substantial increase in conductivity of the TiO2 layer following Li modification. Interfacial modification is done via a simple soaking procedure, and the effect of varying the concentration of Li[CF3SO2](2)N is discussed. We report investigations into optimization and the mechanism of such improvement, for example by varying processing parameters of the modification procedure or the ionic species themselves

Use of the GATE Monte Carlo package for dosimetry applications

6 pages, 3 figures - submitted to NIM A, presented by D. VisvikisInternational audienceOne of the roles for MC simulation studies is in the area of dosimetry. A number of different codes dedicated to dosimetry applications are available and widely used today, such as MCNP, EGSnrc and PTRAN. However, such codes do not easily facilitate the description of complicated 3D sources or emission tomography systems and associated data flow, which may be useful in different dosimetry application domains. Such problems can be overcome by the use of specific MC codes such as GATE, which is based on Geant4 libraries, providing a scripting interface with a number of advantages for the simulation of SPECT and PET systems. Despite this potential, its major disadvantage is in terms of efficiency involving long execution times for applications such as dosimetry. The strong points and disadvantages of GATE in comparison to other dosimetry specific codes are discussed and illustrated in terms of accuracy, efficiency and flexibility. A number of features, such as the use of voxelised and moving sources, as well as developments such as advanced visualisation tools and the development of dose estimation maps allowing GATE to be used for dosimetry applications are presented. In addition, different examples from dosimetry applications with GATE are given. Finally, future directions with respect to the use of GATE for dosimetry applications are outlined

Computational, Integrative, and Comparative Methods for the Elucidation of Genetic Coexpression Networks

Gene expression microarray data can be used for the assembly of genetic coexpression network graphs. Using mRNA samples obtained from recombinant inbred Mus musculus strains, it is possible to integrate allelic variation with molecular and higher-order phenotypes. The depth of quantitative genetic analysis of microarray data can be vastly enhanced utilizing this mouse resource in combination with powerful computational algorithms, platforms, and data repositories. The resulting network graphs transect many levels of biological scale. This approach is illustrated with the extraction of cliques of putatively coregulated genes and their annotation using gene ontology analysis and cis-regulatory element discovery. The causal basis for coregulation is detected through the use of quantitative trait locus mapping

Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping

<p>Abstract</p> <p>Background</p> <p>Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.</p> <p>Methods</p> <p>We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.</p> <p>Results</p> <p>Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the <it>SPRY4-FGF1 </it>locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the <it>TGFBI </it>and <it>SMAD5 </it>genes and rs6897690 is within the <it>SPRY4 </it>gene.</p> <p>Conclusion</p> <p>Our screening of 5q31-32 implicates three potential candidate genes for SZ: <it>SMAD5</it>, <it>TGFBI </it>and <it>SPRY4</it>.</p

Association of copy number variation across the genome with neuropsychiatric traits in the general population

Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. 6807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from SNP-array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia, rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analysed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known schizophrenia CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardised mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p=3e-07 for duplications and by 0.021 [95%CI 0.010, 0.032], p=1e-04 for deletions. In line with published results on educational attainment in ALSPAC, IQ was associated with CNV burden: the SMD per gene affected was -0.017 [95%CI -0.025,-0.008] p=1e-04 for duplications and -0.023 [95%CI -0.037, -0.009], p=0.002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. Schizophrenia-associated deletions were associated with IQ (SMD: -0.617 [95%CI -0.936,-0.298], p=2e-04), but not with PEs or other traits. We found that rare CNV burden and known schizophrenia candidate CNVs are associated with neuropsychiatric phenotypes in a non-clinically ascertained sample of young people

Cognitive performance among carriers of pathogenic copy number variants: analysis of 152,000 UK Biobank subjects

Background The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population. We aimed to examine the effect of neurodevelopmental copy number variants (CNVs) on the cognitive performance of participants. Methods We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. We annotated a list of 93 CNVs and compared their frequencies with control datasets. We analyzed the performance on seven cognitive tests of carriers of 12 CNVs associated with schizophrenia (n = 1087) and of carriers of another 41 neurodevelopmental CNVs (n = 484). Results The frequencies of the 93 CNVs in the Biobank subjects were remarkably similar to those among 26,628 control subjects from other datasets. Carriers of schizophrenia-associated CNVs and of the group of 41 other neurodevelopmental CNVs had impaired performance on the cognitive tests, with nine of 14 comparisons remaining statistically significant after correction for multiple testing. They also had lower educational and occupational attainment (p values between 10−7 and 10−18). The deficits in cognitive performance were modest (Z score reductions between 0.01 and 0.51), compared with individuals with schizophrenia in the Biobank (Z score reductions between 0.35 and 0.90). Conclusions This is the largest study on the cognitive phenotypes of CNVs to date. Adult carriers of neurodevelopmental CNVs from the general population have significant cognitive deficits. The UK Biobank will allow unprecedented opportunities for analysis of further phenotypic consequences of CNVs

The SNPMaP package for R: a framework for genome-wide association using DNA pooling on microarrays

Summary: Large-scale genome-wide association (GWA) studies using thousands of high-density SNP microarrays are becoming an essential tool in the search for loci related to heritable variation in many phenotypes. However, the cost of GWA remains beyond the reach of many researchers. Fortunately, the majority of statistical power can still be obtained by estimating allele frequencies from DNA pools, reducing the cost to that of tens, rather than thousands of arrays. We present a set of software tools for processing SNPMaP (SNP microarrays and pooling) data from CEL files to Relative Allele Scores in the rich R statistical computing environment

Medical consequences of pathogenic CNVs in adults: Analysis of the UK Biobank

Background: Genomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults. Methods: We analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons). Results and conclusions: Many of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV–phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers

New Copy Number Variations in Schizophrenia

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants