Manajemen Program Siaran Lokal Aceh TV Dalam Upaya Penyebarluasan Syariat Islam Dan Pelestarian Budaya Lokal

Managing broadcasting management is not easy. Managing the broadcasting business is a difficult and challenging. This research aims to analyze the activity of management and organizational performance ACEH TV television media in an effort to disseminate the Islamic Sharia and Preservation of Local Culture in Aceh. This research is descriptive qualitative. Informants of this research is managing director, program director, executive producer, cameraman / reporter, as well as additional informants Regional Chairman of the Indonesian Broadcasting Commission (KPID) Aceh, Aceh Province Department of Islamic Law, and local media observers. The location of this research is in Banda Aceh, Aceh province. Sampling was done purposively. Data collected through observation, interviews, and documentation. Data were analyzed by analysis of an interactive model of Miles and Huberman. The results showed that the ACEH TV as the medium of television that is broadcasting management ACEH have done according to a local television broadcasting standard. Agenda setting function of mass media performed in the ACEH TV dissemination of Islamic Shariah in Aceh and local culture to influence the people of Aceh to implement Islamic Sharia and also maintain the culture and local wisdom Aceh. It can be seen from all the programs that are aired ACEH TV is a program of local cultural nuances of Islamic law. There are still some shortcomings in running broadcasting broadcasting technology such as lack of equipment that is increasingly sophisticated. The results of image editing is very simple, and some programs presenter still looks stiff when in front of the camera

Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants.

Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.This work was supported by a Canadian Institute of Health Research (CIHR) team grant awarded to E.G., A.T., M.C.V. and M.L. (TEC-128093) and the CIHR funded Epigeneome Mapping Centre at McGill University (EP1-120608) awarded to T.P. and M.L., and the Swedish Research Council, Knut and Alice Wallenberg Foundation and the Torsten Söderberg Foundation awarded to L.R. F.A. holds studentship from The Research Institute of the McGill University Health Center (MUHC). F.G. is a recipient of a research fellowship award from the Heart and Stroke Foundation of Canada. A.T. is the director of a Research Chair in Bariatric and Metabolic Surgery. M.C.V. is the recipient of the Canada Research Chair in Genomics Applied to Nutrition and Health (Tier 1). E.G. and T.P. are recipients of a Canada Research Chair Tier 2 award. The MuTHER Study was funded by a programme grant from the Wellcome Trust (081917/Z/07/Z) and core funding for the Wellcome Trust Centre for Human Genetics (090532). TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. T.D.S. is a holder of an ERC Advanced Principal Investigator award. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. Finally, we thank the NIH Roadmap Epigenomics Consortium and the Mapping Centers (http://nihroadmap.nih.gov/epigenomics/) for the production of publicly available reference epigenomes. Specifically, we thank the mapping centre at MGH/BROAD for generation of human adipose reference epigenomes used in this study.This is the final version. It was first published by NPG at http://www.nature.com/ncomms/2015/150529/ncomms8211/full/ncomms8211.html#abstrac

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Capturing epigenomes at high-resolution for insight into genome function and metabolic disease risk

Complex diseases such as obesity and related co-morbidities are caused by a combination of underlying predisposing genetic and environmental factors. Genome-wide association studies (GWAS) have revealed complex trait-linked genetic variants with small effect sizes and enriched in non-coding regions, making translation into biological knowledge challenging. Epigenomic traits, such as DNA (CpG) methylation, can be used as a proxy to link genome and environment to phenotype and disease. Past epigenome-wide investigation efforts have mainly profiled bioavailable tissues (i.e. whole blood) using array-based methods that are biased towards CpG-dense regions such as promoters. However, complex trait-associated and tissue-specific CpGs have been found to be enriched in enhancers active in disease-relevant tissues. While whole-genome bisulfite sequencing enables full investigation of methylomes, its current high cost makes its applicability in large-scale epigenome-wide association studies (EWAS) impractical. We implemented a novel next-generation capture sequencing method - MethylC-Capture Sequencing, or MCC-Seq - that permits simultaneous and cost-efficient profiling of methylation and genotypes over user-defined genomic targets (up to 200Mb). We validated the accuracy of the method through technical comparisons with other available techniques. We developed two custom panels targeting up to ~4.5 million CpGs within the adipose-specific functional methylome and ~0.3 million SNPs from the Illumina HumanCore array. This allowed for downstream genotype imputations, thus making MCC-Seq a dual purpose next-generation sequencing method. Using deeply phenotyped population-based and clinical cohorts of visceral adipose tissue and whole blood, we applied MCC-Seq in over 500 samples and revealed unprecedented methylation variants linked to plasma lipid traits in multiple EWAS. We identified 567 lipid-linked regulatory regions and showed that these are enriched in adipose-specific enhancer regions, highlighting the need for an expanded catalog of interrogated distal regulatory regions in complex disease studies. We used the single-base profiling capacity of MCC-Seq to present novel localization patterns of metabolic trait-linked CpGs at regulatory regions and fine-map epigenetic signals from low-density coverage studies of almost 700 independent adipose samples. Through our efforts, we generated unique reference maps of methylome, transcriptome, and chromatin accessibility in the obesity-targeted visceral adipose tissue including isolated adipocytes. We applied integrational approaches using these maps and other ‘omics’ layers to show features of the identified trait-linked regions, highlighting cis-acting regulatory elements that depict putative pleiotropic effects on gene expression levels. We showed that a large proportion (>55%) of lipid-associated adipose regulatory regions are under genetic regulation, with this fraction being strengthened (>93%) at elements replicating in matched bioavailable tissues (i.e. whole blood samples). We further highlighted an enrichment for genetic regulation by GWAS SNPs of metabolic disease-linked traits, including at GALNT2. In all, the findings presented in this thesis show the advantage of using high-resolution epigenetic profiling in regulatory elements active in diseases-relevant tissues to provide novel genetic and epigenetic variants in large-scale studies of complex traits.Les maladies complexes telles que l’obésité et ses comorbidités associées sont causées par l’action commune de facteurs de prédispositions génétiques et environnementaux. Les études d’association pangénomiques (GWAS) ont permis d’identifier des facteurs génétiques communs associés à ces maladies, mais ayant une valeur prédictive limitée. De plus, due à leur localisation dans la portion non codante du génome, ceux-ci sont difficiles à lier aux mécanismes de la pathologie. Les changements épigénétiques, tel que la méthylation de l’ADN (CpG), peuvent être utilisés pour lier la génétique et l’environnement aux phénotypes et maladies complexes. Les études d’association panépigénomiques (EWAS) publiées jusqu’à maintenant ont plutôt profilé des tissus bio-disponibles (ex: sang complet) et employé des méthodes ciblant préférentiellement les régions promotrices du génome. Cependant, des études précédentes ont démontré que les CpGs associés aux traits complexes et spécifiques aux tissus sont enrichis dans les éléments activateurs de tissus liés aux maladies. De plus, le coût élevé du séquençage complet du méthylome (WGBS; whole-genome bisulfite sequencing) rend cette méthode difficilement applicable dans les EWAS à grande échelle. Nous avons implémenté une approche rentable pour la capture de séquençage de prochaine génération - MethylC-Capture Sequencing (MCC-Seq) - permettant de profiler simultanément le méthylome et le génome chevauchant des cibles définies par l’utilisateur (jusqu’à 200Mb). Nous avons validé le degré de précision de la méthode à travers des comparaisons de données de méthylation collectionnées utilisant des techniques établies. Nous avons développé deux panels de capture ciblant jusqu’à 4.5M de CpGs chevauchant le méthylome fonctionnel du tissu adipeux et 0.3M de variants génétiques compris sur le Illumina HumanCore array, permettant ainsi l’imputation de données génétiques additionnelles. Cela démontre que MCC-Seq est une méthode de séquençage à double usage. Utilisant des cohortes bien caractérisées de tissue adipeux viscéral (VAT) et de sang complet, nous avons appliqué MCC-Seq dans plusieurs EWAS permettant l’identification de nouveaux variants épigénomiques corrélés aux niveaux de lipides. Nous avons caractérisé 567 régions régulatrices liées à ces traits complexes étant enrichies parmi les éléments activateurs du tissu adipeux, démontrant ainsi l’utilité d’interroger ces régions régulatrices dans les études des maladies complexes. MCC-Seq a la capacité de profiler chaque base dans les régions capturées, nous permettant ainsi de présenter des motifs de localisation novateurs de variants épigénomiques liés aux traits complexes. De plus, cette méthode permet de cartographier les signaux épigénomiques identifiés par des études antérieures (~700 échantillons de tissu adipeux) ayant utilisé des techniques de profilage à couverture de faible densité. A travers nos études, nous avons généré des références uniques de cartes épigénomiques détaillant les profiles du méthylome, du transcriptome et d’accessibilité de la chromatine du VAT et adipocytes isolés. L’incorporation de ces cartes épigénomiques dans nos analyses nous a permis de caractériser nos régions régulatrices et d’identifier des effets pléiotropiques putatifs les liant à l’expression de gènes. Nous démontrons qu’une grande majorité des régions régulatrices associées aux lipides sont sous contrôle génétique (>55%) et que cette proportion était renforcée (>93%) aux sites répliqués dans des tissus bio-disponibles (ex: sang complet). De plus, nous constatons un enrichissement d’effets génétiques par des variants GWAS liés à des traits métaboliques complexes, incluant GALNT2. En résumé, les résultats présentés dans cette thèse démontrent les avantages de notre méthode pour l’évaluation exhaustive de la variation génétique et épigénétique dans des tissus biologiquement pertinents et leur impact dans la pathologie des maladies complexes

Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation

BACKGROUND: CpG methylation variation is involved in human trait formation and disease susceptibility. Analyses within populations have been biased towards CpG-dense regions through the application of targeted arrays. We generate whole-genome bisulfite sequencing data for approximately 30 adipose and blood samples from monozygotic and dizygotic twins for the characterization of non-genetic and genetic effects at single-site resolution. RESULTS: Purely invariable CpGs display a bimodal distribution with enrichment of unmethylated CpGs and depletion of fully methylated CpGs in promoter and enhancer regions. Population-variable CpGs account for approximately 15–20 % of total CpGs per tissue, are enriched in enhancer-associated regions and depleted in promoters, and single nucleotide polymorphisms at CpGs are a frequent confounder of extreme methylation variation. Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific. Tobacco smoking is associated with differential methylation in blood with no evidence of this exposure impacting cell counts. Opposite to non-genetic effects, genetic effects of CpG methylation are shared across tissues and thus limit inter-tissue epigenetic drift. CpH methylation is rare, and shows similar characteristics of variation patterns as CpGs. CONCLUSIONS: Our study highlights the utility of low pass whole-genome bisulfite sequencing in identifying methylome variation beyond promoter regions, and suggests that targeting the population dynamic methylome of tissues requires assessment of understudied intergenic CpGs distal to gene promoters to reveal the full extent of inter-individual variation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0856-1) contains supplementary material, which is available to authorized users

Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer

Background: a regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. Methods: we randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. Results: ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). Conclusions: in patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival