Acute Malnutrition and Under-5 Mortality, Northeastern Part of India.

We assessed the prevalence of childhood acute malnutrition and under-five mortality rate (U5MR) in Darbhanga district, India, using a two-stage 49-cluster household survey. A total of 1379 households comprising 8473 people were interviewed. During a 90-day recall period, U5MR was 0.5 [95% confidence interval (CI), 0.2-1.4] per 10 000 per day. The prevalence of global acute malnutrition among 1405 children aged 6-59 months was 15.4% (NCHS) and 19.4% (2006 WHO references). This survey suggests that in Darbhanga district, the population is in a borderline food crisis with few food resources. Appropriate strategies should be developed to improve the overall nutritional and health status of children

Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies

BACKGROUND: Very few data on anti-malarial efficacy are available from the Democratic Republic of Congo (DRC). DRC changed its anti-malarial treatment policy to amodiaquine (AQ) and artesunate (AS) in 2005. METHODS: The results of two in vivo efficacy studies, which tested AQ and sulphadoxine-pyrimethamine (SP) monotherapies and AS+SP and AS+AQ combinations in Boende (Equatorial province), and AS+SP, AS+AQ and SP in Kabalo (Katanga province), between 2003 and 2004 are presented. The methodology followed the WHO 2003 protocol for assessing the efficacy of anti-malarials in areas of high transmission. RESULTS: Out of 394 included patients in Boende, the failure rates on day 28 after PCR-genotyping adjustment of AS+SP and AS+AQ were estimated as 24.6% [95% CI: 16.6-35.5] and 15.1% [95% CI: 8.6-25.7], respectively. For the monotherapies, failure rates were 35.9% [95% CI: 27.0-46.7] for SP and 18.3% [95% CI: 11.6-28.1] for AQ. Out of 207 patients enrolled in Kabalo, the failure rate on day 28 after PCR-genotyping adjustment was 0 [1-sided 95% CI: 5.8] for AS+SP and AS+AQ [1-sided 95% CI: 6.2]. It was 19.6% [95% CI: 11.4-32.7] for SP monotherapy. CONCLUSION: The finding of varying efficacy of the same combinations at two sites in one country highlights one difficulty of implementing a uniform national treatment policy in a large country. The poor efficacy of AS+AQ in Boende should alert the national programme to foci of resistance and emphasizes the need for systems for the prospective monitoring of treatment efficacy at sentinel sites in the country

Towards the QFT on Curved Spacetime Limit of QGR. I: A General Scheme

In this article and a companion paper we address the question of how one might obtain the semiclassical limit of ordinary matter quantum fields (QFT) propagating on curved spacetimes (CST) from full fledged Quantum General Relativity (QGR), starting from first principles. We stress that we do not claim to have a satisfactory answer to this question, rather our intention is to ignite a discussion by displaying the problems that have to be solved when carrying out such a program. In the present paper we propose a scheme that one might follow in order to arrive at such a limit. We discuss the technical and conceptual problems that arise in doing so and how they can be solved in principle. As to be expected, completely new issues arise due to the fact that QGR is a background independent theory. For instance, fundamentally the notion of a photon involves not only the Maxwell quantum field but also the metric operator - in a sense, there is no photon vacuum state but a "photon vacuum operator"! While in this first paper we focus on conceptual and abstract aspects, for instance the definition of (fundamental) n-particle states (e.g. photons), in the second paper we perform detailed calculations including, among other things, coherent state expectation values and propagation on random lattices. These calculations serve as an illustration of how far one can get with present mathematical techniques. Although they result in detailed predictions for the size of first quantum corrections such as the gamma-ray burst effect, these predictions should not be taken too seriously because a) the calculations are carried out at the kinematical level only and b) while we can classify the amount of freedom in our constructions, the analysis of the physical significance of possible choices has just begun.Comment: LaTeX, 47 p., 3 figure

KRAB–Zinc Finger Proteins and KAP1 Can Mediate Long-Range Transcriptional Repression through Heterochromatin Spreading

Krüppel-associated box domain-zinc finger proteins (KRAB–ZFPs) are tetrapod-specific transcriptional repressors encoded in the hundreds by the human genome. In order to explore their as yet ill-defined impact on gene expression, we developed an ectopic repressor assay, allowing the study of KRAB–mediated transcriptional regulation at hundreds of different transcriptional units. By targeting a drug-controllable KRAB–containing repressor to gene-trapping lentiviral vectors, we demonstrate that KRAB and its corepressor KAP1 can silence promoters located several tens of kilobases (kb) away from their DNA binding sites, with an efficiency which is generally higher for promoters located within 15 kb or less. Silenced promoters exhibit a loss of histone H3-acetylation, an increase in H3 lysine 9 trimethylation (H3K9me3), and a drop in RNA Pol II recruitment, consistent with a block of transcriptional initiation following the establishment of silencing marks. Furthermore, we reveal that KRAB–mediated repression is established by the long-range spreading of H3K9me3 and heterochromatin protein 1 β (HP1β) between the repressor binding site and the promoter. We confirm the biological relevance of this phenomenon by documenting KAP1–dependent transcriptional repression at an endogenous KRAB–ZFP gene cluster, where KAP1 binds to the 3′ end of genes and mediates propagation of H3K9me3 and HP1β towards their 5′ end. Together, our data support a model in which KRAB/KAP1 recruitment induces long-range repression through the spread of heterochromatin. This finding not only suggests auto-regulatory mechanisms in the control of KRAB–ZFP gene clusters, but also provides important cues for interpreting future genome-wide DNA binding data of KRAB–ZFPs and KAP1

A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.

AbstractBACKGROUND: KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences.METHOD: To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression.RESULTS: We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression