Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review

Background: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. Methodology/Principal Findings: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. Conclusion/Significance: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries

On the Complexity of Scheduling in Wireless Networks

We consider the problem of throughput-optimal scheduling in wireless networks subject to interference constraints. We model the interference using a family of K-hop interference models, under which no two links within a K-hop distance can successfully transmit at the same time. For a given K, we can obtain a throughput-optimal scheduling policy by solving the well-known maximum weighted matching problem. We show that for K > 1, the resulting problems are NP-Hard that cannot be approximated within a factor that grows polynomially with the number of nodes. Interestingly, for geometric unit-disk graphs that can be used to describe a wide range of wireless networks, the problems admit polynomial time approximation schemes within a factor arbitrarily close to 1. In these network settings, we also show that a simple greedy algorithm can provide a 49-approximation, and the maximal matching scheduling policy, which can be easily implemented in a distributed fashion, achieves a guaranteed fraction of the capacity region for "all K." The geometric constraints are crucial to obtain these throughput guarantees. These results are encouraging as they suggest that one can develop low-complexity distributed algorithms to achieve near-optimal throughput for a wide range of wireless networksopen1

Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences

Pax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions. Here we provide evidence that the genomes of many other vertebrate species contain multiple Pax6 loci. We sequenced Pax6-containing BACs from the cartilaginous elephant shark (Callorhinchus milii) and found two distinct Pax6 loci. Pax6.1 is highly similar to mammalian Pax6, while Pax6.2 encodes a paired-less Pax6. Using synteny relationships, we identify homologs of this novel paired-less Pax6.2 gene in lizard and in frog, as well as in zebrafish and in other teleosts. In zebrafish two full-length Pax6 duplicates were known previously, originating from the fish-specific genome duplication (FSGD) and expressed in divergent patterns due to paralog-specific loss of cis-elements. We show that teleosts other than zebrafish also maintain duplicate full-length Pax6 loci, but differences in gene and regulatory domain structure suggest that these Pax6 paralogs originate from a more ancient duplication event and are hence renamed as Pax6.3. Sequence comparisons between mammalian and elephant shark Pax6.1 loci highlight the presence of short- and long-range conserved noncoding elements (CNEs). Functional analysis demonstrates the ancient role of long-range enhancers for Pax6 transcription. We show that the paired-less Pax6.2 ortholog in zebrafish is expressed specifically in the developing retina. Transgenic analysis of elephant shark and zebrafish Pax6.2 CNEs with homology to the mouse NRE/Pα internal promoter revealed highly specific retinal expression. Finally, morpholino depletion of zebrafish Pax6.2 resulted in a "small eye" phenotype, supporting a role in retinal development. In summary, our study reveals that the pleiotropic functions of Pax6 in vertebrates are served by a divergent family of Pax6 genes, forged by ancient duplication events and by independent, lineage-specific gene losses

Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely

Multiple reactions in vanadyl-V(IV) oxidation by H2O2H_2O_2

Oxidation of vanadyl sulfate by $H_2O_2$ involves multiple reactions at neutral pH conditions. The primary reaction was found to be oxidation of V(IV) to V(V) using 0.5 equivalent of $H_2O_2$, based on the loss of blue color and the visible spectrum. The loss of V(IV) and formation V(V) compounds were confirmed by ESR and $^{51}V$-NMR spectra, respectively. In the presence of excess $H_2O_2$ (more than two equivalents), the V(V) was converted into diperoxovanadate, the major end-product of these reactions, identified by changes in absorbance in ultraviolet region and by the specific chemical shift in NMR spectrum. The stoichiometric studies on the $H_2O_2$ consumed in this reaction support the occurrence of reactions of two-electron oxidation followed by complexing two molecules of $H_2O_2$. Addition of a variety of compounds—Tris, ethanol, mannitol, benzoate, formate (hydroxyl radical quenching), histidine, imidazole (singlet oxygen quenching), and citrate—stimulated a secondary reaction of oxygen-consumption that also used V(IV) as the reducing source. This reaction requires concomitant oxidation of vanadyl by $H_2O_2$, favoured at low $H_2O_2$:V(IV) ratio. Another secondary reaction of oxygen release was found to occur during vanadyl oxidation by $H_2O_2$ in acidic medium in which the end-product was not diperoxovanadate but appears to be a mixture of $VO^+_3$ (–546 ppm), $VO^{3+}$ (–531 ppm) and $VO_2^+$ (–512 ppm), as shown by the $^{51}V$-NMR spectrum. This reaction also occurred in phosphate-buffered medium but only on second addition of vanadyl. The compounds that stimulated the oxygen-consumption reaction were found to inhibit the oxygen-release reaction. A combination of these reactions occur depending on the proportion of the reactants (vanadyl and $H_2O_2$), the pH of the medium and the presence of some compounds that affect the secondary reactions

Master process sheets for fabrication of CFC centre fuselage parts of TEJAS (Light Combat Aircraft): part-3

The centre fuselage has a complex geometry with doubly curved surfaces. This presents a greater challenge in the realization of airworthy composite components. The mould ability of composites is exploited to produce composite tools, which capture the complex geometry. These parts have non-developable surfaces, which are not amenable for lay-up with computer generated transfer foils. The lay-up is done using prepregs of smaller width, which is similar to tow placement, to facilitate the lay-up. The technology to produce these complex composite components is developed over a period of time. The tools required for the layup at critical areas, assembly of cores on skin are developed to facilitate faster and controlled production. The fine tuned process for Series Production of ACA is documented in greater details with step-by-step operations augmented with figures to assist the production at shop floor