Ivermectin for onchocercal eye disease (river blindness).

BACKGROUND: It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear. OBJECTIVES: The aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary aim was to assess the effects of ivermectin on lesions affecting the eye in onchocerciasis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 3), MEDLINE (January 1950 to April 2012), EMBASE (January 1980 to April 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 April 2012. SELECTION CRITERIA: We included randomised controlled trials with at least one year of follow-up comparing ivermectin with placebo or no treatment. Participants in the trials were people normally resident in endemic onchocercal communities with or without one or more characteristic signs of ocular onchocerciasis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. As trials varied in design and setting, we were unable to perform a meta-analysis. MAIN RESULTS: The review included four trials: two small studies (n = 398) in which people with onchocercal infection were given one dose of ivermectin or placebo and followed up for one year; and two larger community-based studies (n = 4941) whereby all individuals in selected communities were treated every six or 12 months with ivermectin or placebo, whether or not they were infected, and followed for two to three years. The studies provide evidence that treating people who have onchocerciasis with ivermectin reduces the number of microfilariae in their skin and eye(s) and reduces the number of punctate opacities. There was weaker evidence that ivermectin reduced the risk of chorioretinitis. The studies were too small and of too short a duration to provide evidence for an effect on sclerosing keratitis, iridocyclitis, optic nerve disease or visual loss. One community-based study in communities mesoendemic for the savannah strain of O.volvulus provided evidence that annual mass treatment with ivermectin reduces the risk of new cases of optic nerve disease and visual field loss. The other community-based study of mass biannual treatment of ivermectin in communities affected by the forest strain of O.volvulus demonstrated reductions in microfilarial load, punctate keratitis and iridocyclitis but not sclerosing keratitis, chorioretinitis, optic atrophy or visual impairment. The study was underpowered to estimate the effect of ivermectin on visual impairment and other less frequent clinical signs. The studies included in this review reported some adverse effects, in particular an increased risk of postural hypotension in people treated with ivermectin. AUTHORS' CONCLUSIONS: The lack of evidence for prevention of visual impairment and blindness should not be interpreted to mean that ivermectin is not effective, however, clearly this is a key question that remains unanswered. The main evidence for a protective effect of mass treatment with ivermectin on visual field loss and optic nerve disease comes from communities mesoendemic for the savannah strain of O.volvulus. Whether these findings can be applied to communities with different endemicity and affected by the forest strain is unclear. Serious adverse effects were rarely reported. None of the studies, however, were conducted in areas where people are infected with Loa loa (loiasis)

New upper bounds on sphere packings II

We continue the study of the linear programming bounds for sphere packing introduced by Cohn and Elkies. We use theta series to give another proof of the principal theorem, and present some related results and conjectures.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol6/paper10.abs.htm

What is the Cost of a Preschool Program?

State and local governments that wish to establish or improve preschool programs need cost estimates to evaluate the magnitude of appropriations required. Yet even a casual scrutiny of available expenditure data reveals an enormous variance between the most expensive and least expensive preschool provisions. The purpose of this paper is to delineate the root causes of differences in per-student costs of states’ preschool programs and to suggest cost tradeoffs as different features such as smaller class size or longer school days are introduced or substituted for each other. These cost findings are contrasted with recent meta-analyses of the effectiveness of different program provisions. The goal of this paper is to advance the still nascent body of research on preschool cost effectiveness, and to aid state or local governments to assess the mix of characteristics that are most effective for any given budget constraint. The paper builds partially on the authors’ previous analysis of international preschool programs

Comparing Costs of Early Childhood Care and Education Programs: An International Perspective

The purpose of this article is to outline the determinants of early childhood care and education (EccE) costs as well as a method for measuring them, and to set out available cost data provided by countries for their EccE endeavors. The analysis is based upon comparison of available data for 17 countries. We first address why costs may differ significantly for EccE from country to country. Second, we address why existing reporting of costs is highly inconsistent and typically incomplete, including an examination of disparities in reported EccE expenditures across countries. Third, we outline an appropriate way, known as the “ingredients method”, for determining costs that can provide consistent measurement for comparative purposes

Long-Term Dynamics of the Kidney Disease Epidemic Among HIV-Infected Individuals

One of many risks facing HIV+ individuals is the development of kidney dysfunction and end stage kidney disease (ESKD). A differential equation-based mathematical model was developed to assess the impact of antiretroviral therapy on the progression to kidney disease and on reducing mortality due to kidney failure. Analytical and numerical predictions of long-term HIV+ ESKD prevalence show that therapy can lead to either extremely low levels of disease prevalence or increased prevalence, depending on drug efficacy levels and mechanisms of action. Maintenance of HIV+ ESKD prevalence below one individual is possible with sufficient efficacy (e.g., 99%) against the progression from AIDS to HIV+ ESKD and against entry to the AIDS population, when the reduction in mortality in the AIDS and HIV+ ESKD populations is modest (e.g., 10%). However, the concomitant decrease in mortality in the AIDS and HIV+ ESKD populations due to therapy is predicted to sustain greater disease prevalence

Integrated Intermodal Passenger Transportation System

Modern transportation consists of many unique modes of travel. Each of these modes and their respective industries has evolved independently over time, forming a largely incoherent and inefficient overall transportation system. Travelers today are forced to spend unnecessary time and efforts planning a trip through varying modes of travel each with their own scheduling, pricing, and services; causing many travelers to simply rely on their relatively inefficient and expensive personal automobile. This paper presents a demonstration program system to not only collect and format many different sources of trip planning information, but also combine these independent modes of travel in order to form optimal routes and itineraries of travel. The results of this system show a mean decrease in inter-city travel time of 10 percent and a 25 percent reduction in carbon dioxide emissions over personal automobiles. Additionally, a 55 percent reduction in carbon dioxide emissions is observed for intra-city travel. A conclusion is that current resources are available, if somewhat hidden, to drastically improve point to point transportation in terms of time spent traveling, the cost of travel, and the ecological impact of a trip. Finally, future concepts are considered which could dramatically improve the interoperability and efficiency of the transportation infrastructure

A Review of Three-Family Grand Unified String Models

We review the construction and classification of three-family grand unified models within the framework of asymmetric orbifolds in perturbative heterotic superstring. We give a detailed survey of all such models which is organized to aid analysis of their phenomenological properties. We compute tree-level superpotentials for these models. These superpotentials are used to analyze the issues of proton stability (doublet-triplet splitting and R-parity violating terms) and Yukawa mass matrices. To have agreement with phenomenological data all these models seem to require certain degree of fine-tuning. We also analyze the possible patterns of supersymmetry breaking in these models. We find that the supersymmetry breaking scale comes out either too high to explain the electroweak hierarchy problem, or below the electroweak scale unless some degree of fine-tuning is involved. Thus, none of the models at hand seem to be phenomenologically flawless.Comment: 49 pages, Revtex 3.0; one ps figure included. To appear in the Review section of Int.J.Mod.Phy