Celiac disease as a potential cause of idiopathic portal hypertension: a case report

<p>Abstract</p> <p>Introduction</p> <p>Idiopathic portal hypertension is a disorder of unknown etiology, clinically characterized by portal hypertension, splenomegaly and anemia secondary to hypersplenism.</p> <p>Case presentation</p> <p>A 54-year-old man was admitted to our hospital for evaluation of malaise, weight loss, abdominal swelling and lower limb edema. His paraclinical tests revealed pancytopenia, large ascites, splenomegaly and esophageal varices consistent with portal hypertension. Duodenal biopsy and serologic findings were compatible with celiac disease. His symptoms improved on a gluten-free diet, but his clinical course was further complicated with ulcerative jejunoileitis, and intestinal T-cell lymphoma.</p> <p>Conclusion</p> <p>It seems that celiac disease, by an increased immune reaction in the splenoportal axis, can result in the development of idiopathic portal hypertension in susceptible affected patients.</p

Are we doing enough? Evaluation of the Polio Eradication Initiative in a district of Pakistan's Punjab province: a LQAS study

<p>Abstract</p> <p>Background</p> <p>The success of the Global Polio Eradication Initiative was remarkable, but four countries - Afghanistan, Pakistan, India and Nigeria - never interrupted polio transmission. Pakistan reportedly achieved all milestones except interrupting virus transmission. The aim of the study was to establish valid and reliable estimate for: routine oral polio vaccine (OPV) coverage, logistics management and the quality of monitoring systems in health facilities, NIDs OPV coverage, the quality of NIDs service delivery in static centers and mobile teams, and to ultimately provide scientific evidence for tailoring future interventions.</p> <p>Methods</p> <p>A cross-sectional study using lot quality assessment sampling was conducted in the District Nankana Sahib of Pakistan's Punjab province. Twenty primary health centers and their catchment areas were selected randomly as <it>'lots'</it>. The study involved the evaluation of 1080 children aged 12-23 months for routine OPV coverage, 20 health centers for logistics management and quality of monitoring systems, 420 households for NIDs OPV coverage, 20 static centers and 20 mobile teams for quality of NIDs service delivery. Study instruments were designed according to WHO guidelines.</p> <p>Results</p> <p>Five out of twenty lots were rejected for unacceptably low routine immunization coverage. The validity of coverage was questionable to extent that all lots were rejected. Among the 54.1% who were able to present immunization cards, only 74.0% had valid immunization. Routine coverage was significantly associated with card availability and socioeconomic factors. The main reasons for routine immunization failure were absence of a vaccinator and unawareness of need for immunization. Health workers (96.9%) were a major source of information. All of the 20 lots were rejected for poor compliance in logistics management and quality of monitoring systems. Mean compliance score and compliance percentage for logistics management were 5.4 ± 2.0 (scale 0-9) and 59.4% while those for quality of monitoring systems were 3.3 ± 1.2 (scale 0-6) and 54.2%. The 15 out of 20 lots were rejected for unacceptably low NIDs coverage by finger-mark. All of the 20 lots were rejected for poor NIDs service delivery (mean compliance score = 11.7 ± 2.1 [scale 0-16]; compliance percentage = 72.8%).</p> <p>Conclusion</p> <p>Low coverage, both routine and during NIDs, and poor quality of logistics management, monitoring systems and NIDs service delivery were highlighted as major constraints in polio eradication and these should be considered in prioritizing future strategies.</p

From their own perspective - constraints in the Polio Eradication Initiative: perceptions of health workers and managers in a district of Pakistan's Punjab province

<p>Abstract</p> <p>Background</p> <p>The success of the Global Polio Eradication Initiative was remarkable, but four countries - Afghanistan, Pakistan, India and Nigeria - never interrupted polio transmission. Pakistan reportedly achieved all milestones except interrupting virus transmission. This paper describes the perceptions of health workers and managers regarding constraints in the Polio Eradication Initiative (PEI) to ultimately provide evidence for designing future interventions.</p> <p>Methods</p> <p>A qualitative cross-sectional study using focus group discussions and in-depth interviews was conducted in the Nankana Sahib District of Pakistan's Punjab province. Study subjects included staff at all levels in the PEI at district headquarters, in all 4 tehsils (sub-districts) and at 20 randomly selected primary health centers. In total, 4 FGD and 7 interview sessions were conducted and individual session summary notes were prepared and later synthesized, consolidated and subjected to conceptual analysis.</p> <p>Results</p> <p>The main constraints identified in the study were the poor condition of the cold chain in all aspects, poor skills and a lack of authority in resource allocation and human resource management, limited advocacy and communication resources, a lack of skills and training among staff at all levels in the PEI/EPI in almost all aspects of the program, a deficiency of public health professionals, poor health services structure, administrative issues (including ineffective means of performance evaluation, bureaucratic and political influences, problems in vaccination areas and field programs, no birth records at health facilities, and poor linkage between different preventive programs), unreliable reporting and poor monitoring and supervision systems, limited use of local data for interventions, and unclear roles and responsibilities after decentralization.</p> <p>Conclusion</p> <p>The study highlights various shortcomings and bottlenecks in the PEI, and the barriers identified should be considered in prioritizing future strategies.</p

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis