Network Meta-Analysis Using R: A Review of Currently Available Automated Packages

Network meta-analysis (NMA) – a statistical technique that allows comparison of multiple treatments in the same meta-analysis simultaneously – has become increasingly popular in the medical literature in recent years. The statistical methodology underpinning this technique and software tools for implementing the methods are evolving. Both commercial and freely available statistical software packages have been developed to facilitate the statistical computations using NMA with varying degrees of functionality and ease of use. This paper aims to introduce the reader to three R packages, namely, gemtc, pcnetmeta, and netmeta, which are freely available software tools implemented in R. Each automates the process of performing NMA so that users can perform the analysis with minimal computational effort. We present, compare and contrast the availability and functionality of different important features of NMA in these three packages so that clinical investigators and researchers can determine which R packages to implement depending on their analysis needs. Four summary tables detailing (i) data input and network plotting, (ii) modeling options, (iii) assumption checking and diagnostic testing, and (iv) inference and reporting tools, are provided, along with an analysis of a previously published dataset to illustrate the outputs available from each package. We demonstrate that each of the three packages provides a useful set of tools, and combined provide users with nearly all functionality that might be desired when conducting a NMA.     

Mass Vaccination with a New,Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

Introduction

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.

Methods

All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.

Results

The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.

Discussion

This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.     

Lipid interactions of an actinoporin pore-forming oligomer

The actinoporins are cytolytic toxins produced by sea anemones. Upon encountering a membrane, preferably containing sphingomyelin, they oligomerize and insert their N-terminal helix into the membrane, forming a pore. Whether sphingomyelin is specifically recognized by the protein or simply induces phase coexistence in the membrane has been debated. Here, we perform multi-microsecond molecular dynamics simulations of an octamer of fragaceatoxin C, a member of the actinoporin family, in lipid bilayers containing either pure 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or a 1:1 mixture of DOPC and palmitoyl sphingomyelin (PSM). The complex is highly stable in both environments, with only slight fraying of the inserted helices near their N-termini. Analyzing the structural parameters of the mixed membrane in the course of the simulation, we see signs of a phase transition for PSM in the inner leaflet of the bilayer. In both leaflets, cross-interactions between lipids of different type decrease over time. Surprisingly, the aromatic loop thought to be responsible for sphingomyelin recognition interacts more with DOPC than PSM by the end of the simulation. These results support the notion that the key membrane property that actinoporins recognize is lipid phase coexistence.     

Phenological variation in height growth and needle unfolding of Smith fir along an altitudinal gradient on the southeastern Tibetan Plateau

Little is known about variations in tree phenology and their driving forces on the Tibetan Plateau. Herein, we monitored shoot growth and needle unfolding of Smith fir (Abies georgei var. smithii) between 3,800 and 4,360 m a.s.l. in the Sygera Mountains, southeastern Tibetan Plateau. The trees were 0.45–1.48 m high and 12–39 years old. Their phenology was observed every week between May 5 and August 26, 2011. With increasing elevation, shoot growth and needle unfolding started increasingly later, thus indicating a thermal driving force. Although the weekly shoot increment was decreasing with increasing elevation, height growth at various elevations ended in the same week, implying other factors than temperature being responsible for the end of height growth. The accumulated heat sum for the onset of shoot growth appeared to be lower between 4,200 and 4,360 m than between 3,800 and 4,000 m. The anticipated spring warming will likely induce an earlier onset of shoot growth, whereas shoot growth will apparently not benefit from autumn warming. However, the lack of long-term data records precluded a robust statistical test of the underlying cause-and-effect relationships involved in the phenological variations of height growth and needle unfolding.     

Production and purification of extracellular chitinases from Penicillium aculeatum NRRL 2129 under solid-state fermentation

Fourteen Penicillium strains have been screened on wheat bran–crude chitin mixture medium for extracellular chitinase production in solid-state fermentation. Under the experimental conditions tested, Penicillium aculeatum NRRL 2129 (=ATCC 10409) was selected as the best enzyme producer. The optimum incubation period for chitinase production by the potent organism was found to be 72 h. Chromatofocusing was performed as the first step in the purification scheme, but high amount of contaminating proteins interfered with the method. Hence, ion-exchange chromatography experiments were carried out followed by gel filtration to separate and isolate chitinase isoenzymes. Four major chitinase peaks of molecular weight 82.7, 44.6, 28.2 and 26.9 kDa were observed after gel filtration chromatography while, on SDS-PAGE, three protein bands of molecular weights 82.6, 33.9 and 29.1 kDa were identified. The purified enzyme showed optimal temperature and pH at 50 and 5.5 °C, respectively.     

Functional characterization of orf6 and orf9 genes involved in the biosynthesis of L-oleandrose from Streptomyces antibioticus Tü99

Two genes, orf6 and orf9 located in the L-oleandrose sugar biosynthetic gene cluster of Streptomyces antibioticus Tü99. NovU has been characterized as C-5 methyltrnaferase involved in noviose biosynthetic pathway. We have cloned and heterologously expressed the orf6, orf9, and novU genes in S. venezuelae YJ003-OTBP1. This established the function of orf6 and orf9 as 4-ketoreductase and 3-epimerase, respectively. All of analytical data of the noviosylated 10-deoxymethynolide also is in support of proving their functions. Furthermore biosynthetic pathway 5,5-gem-dimethyl-6-deoxyglucose (TDP-Lnoviose) has been proposed.     

Production of a Pseudomonas lipase in n-alkane substrate and its isolation using an improved ammonium sulfate precipitation technique

Among the various lipidic and non-lipidic substances, normal alkanes within the chain lengths of C-12 to C-20 served as the best carbon substrates for the production of extracellular lipase by Pseudomonas species G6. Maximum lipase production of 25 U/ml of the culture broth was obtained by using n-hexadecane as the sole carbon substrate. The optimum pH of 8 and temperature of 34 + 1 degrees C were demonstrated for the production of lipase in n-hexadecane substrate. The optimum concentration of iron, which played a critical role on the lipase production, was found to be 0.25 mg/l. Lipase production could be enhanced to nearly 2.4-fold by using tributyrin at a concentration of 0.05% (v/v) in the culture medium. High recovery of the lipase protein (83%) from the culture broth was achieved by treating the culture supernatant with Silicone 21 Defoamer followed by ammonium sulfate (60% saturation) fractionation.     

Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line

The development of radio-resistant tumor cells might be overcome by the use of tumor selective cytotoxic agents in combination with radiation treatment of cancer. Thus, we are exploring the radiomodifying potential of D7, a tumor-inhibitory compound derived from a plant product, diospyrin, in breast carcinoma cells, MCF-7. The present study indicated that D7 could enhance the radiation-induced cytotoxicity and apoptosis through down-regulation of the anti-apoptotic Bcl-2 and COX-2 gene expression, and up-regulation of pro-apoptotic genes, like p53 and p21. The higher expression of PUMA, a pro-apoptotic protein was also observed in the combination treatment. Effect of D7 on up-regulation of p21 expression in irradiated MCF-7 cells was concomitant with the cell cycle arrest in the G1 phase. Thus, it was concluded that D7 could sensitize the effect of radiation in breast carcinoma by regulating the gene expression involved in cell cycle and apoptosis.