Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and$3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and$8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and$74, respectively, versus $4438 and$102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks

A study of the effect of sudden cooling on tension development by the anterior byssus retractor muscle of mytilus edulis

The effect of ambient temperature on the ACh-induced tension response of the ABRM of Mytilus edulis was examined. The latter was found to have many temperature dependent variables, these included the latent period, the rate of tension development, maximum tension and the relaxation rate. Pmax was found to show a negative temperature coefficent. K+ contractures also showed a negative temperature co-efficent, Pmax approximately doubling for a 20°C decrease in temperature. The application of a cold shock during an ACh-induced contraction-relaxation cycle resulted in a transient increase in tension, the CIC. The production of a CTC was found to be dependent on the immediate presence of a stimulant, the time of application of the cold shock after the addition of stimulant, muscle length and temperature difference. As the temperature difference (ΔT) between the initial and cold shock solutions increased so the size of the CIC increased. The production of a CIC was found not to be directly related to the ACh or to the active state level yet it did not appear to be a passive phenomenon. A CIC was not produced when cold shock was applied to a muscle at rest or during catchy however, when catch was abolished by the application of relaxant a CIC could once again be elicited. Kinetic analysis of the CIC showed that, however, complex the mechanism two steps appear to be rate limiting, and the increase in tension with increasing AT was probably due to an increase in the availability of activator responsible for its production, rather than a differential effect on one of the rate limiting steps. Although it is conceivable that cold shock may exert a direct effect on the contractile proteins, evidence from the literature, and the experiments reported here, suggest that it is more likely that the CTC results from a transient increase in the level of myoplasmic Ca+2 Pharmacological investigation did not disprove this hypothesis. Of the possible sources of Ca+2 responsible for the CIC membrane associated sites seemed the most likely since under conditions which deplete this site no CIC was observed. Also the involvement of cAMP in the production of the CIC was largely excluded

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Maternal Knowledge of Stunting in Rural Indonesia

Child undernutrition and stunting remain serious public health problems in Indonesia. According to the Health Belief Model, increasing mothers’ knowledge of stunting is fundamental to establishing accurate threat perceptions predictive of behavior change. The purpose of this study was to increase understanding of factors related to maternal knowledge of stunting in Indonesia by addressing three questions: 1) How familiar with stunting are Indonesian mothers? 2) What antecedent factors do Indonesian mothers associate with stunting? and 3) What health effects do Indonesian mothers associate with stunting? A total of 3,150 mothers participated in structured face-to-face interviews. Study measures targeted four main variables. Mothers were asked: 1) Have you heard of stunting?; 2) Have you heard of shortness?; 3) What causes stunting/shortness?; and 4) What are the effects of stunting? Only 66 (2.1%) mothers reported having heard of, read about, or knew something about stunting. Approximately two-thirds of participants attributed stunting to hereditary factors. Interrupted growth (33.7%), idiocy (13.8%), and easy to get sick (11.8%) were identified as health effects of stunting. Results highlight the need for health promotion and education efforts focused on increasing basic knowledge of stunting, its causes, and its health effects among Indonesian mothers

Increased Maternal Education and Knowledge of Nutrition and Reductions in Poverty are Associated with Dietary Diversity and Meal Frequency in an Observational Study of Indonesian Children

Background: Optimal infant and young child feeding during the first two years of life is essential to optimum child development and health. While the link between feeding practices and child health outcomes is well documented, little is known about the determinants of these feeding practices in Indonesia. The purpose of this study was to better understand factors associated with appropriate child feeding among Indonesian children 6–23 months of age.Methods: Interviewers conducted interviews with 1498 mothers of children 6–23 months of age to identify practices. Measures of feeding practices included dietary diversity, meal frequency, and minimum acceptable diet. Multivariate logistic regression was used to identify factors associated with dietary diversity and separately with meal frequency.Results: After adjusting for covariates, increased maternal education was associated with improved dietary diversity. Age of child [OR=1.11], knowledge of stunting [OR=1.80], and having ever received nutrition information [OR=1.89] were also associated with greater dietary diversity. Wealth [OR=0.86] and age of child [OR=0.92] were inversely associated with meal frequency. Maternal education, age of child, being a male child, knowledge of stunting, and having received nutrition information increased the odds of the child consuming a minimum acceptable diet.Conclusion: Increasing maternal education, knowledge of stunting, and knowledge of nutrition may improve dietary diversity while poverty alleviation has the potential to improve minimum meal frequency. These findings corroborate similar studies and confirm the importance of government efforts that help girls stay in school, improve families’ understanding of nutrition, and reduce poverty