Global prevalence of childhood cataract: a systematic review

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes

The Winchcombe meteorite, a unique and pristine witness from the outer solar system.

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid. Recovered only hours after falling, the composition of the Winchcombe meteorite is largely unmodified by the terrestrial environment. It contains abundant hydrated silicates formed during fluid-rock reactions, and carbon- and nitrogen-bearing organic matter including soluble protein amino acids. The near-pristine hydrogen isotopic composition of the Winchcombe meteorite is comparable to the terrestrial hydrosphere, providing further evidence that volatile-rich carbonaceous asteroids played an important role in the origin of Earth's water

Identification and characterization of a direct activator of a gene transfer agent

Gene transfer agents (GTAs) are thought to be ancient bacteriophages that have been co-opted into serving their host and can now transfer any gene between bacteria. Production of GTAs is controlled by several global regulators through unclear mechanisms. In Rhodobacter capsulatus, gene rcc01865 encodes a putative regulatory protein that is essential for GTA production. Here, I show that rcc01865 (hereafter gafA) encodes a transcriptional regulator that binds to the GTA promoter to initiate production of structural and DNA packaging components. Expression of gafA is in turn controlled by the pleiotropic regulator protein CtrA and the quorum-sensing regulator GtaR. GafA and CtrA work together to promote GTA maturation and eventual release through cell lysis. Identification of GafA as a direct GTA regulator allows the first integrated regulatory model to be proposed and paves the way for discovery of GTAs in other species that possess gafA homologues

A phase I study of pazopanib in patients with advanced hepatocellular carcinoma

This journal suppl. contain 2009 ASCO Meeting AbstractsOpen Access JournalBACKGROUND: Patients (pts) with advanced hepatocellular carcinoma (HCC) have a poor prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors including VEGF and VEGFR. Pazopanib (GW786034 ) is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit. A Phase I study was conducted to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics and efficacy of pazopanib in patients with locally unresectable and/or …link_to_OA_fulltex

Phase I dose-finding study of pazopanib in hepatocellular carcinoma: Evaluation of early efficacy, pharmacokinetics, and pharmacodynamics

Background: A phase I dose-escalating study of pazopanib was conducted to determine the maximum tolerated dose (MTD), pharmacokinetic/pharmacodynamic relationships, and clinical activity in patients with advanced hepatocellular carcinoma (HCC). Experimental Design: Asian patients (N = 28) were dose escalated on pazopanib (200-800 mg) once daily (QD) on 21-day cycles, with MTD as the primary endpoint using a modified 3 + 3 design. Changes in tumor vasculature were evaluated by dynamic contrast-enhanced MRI (DCE-MRI). Results: Two of five patients at the 800-mg dose level experienced dose-limiting toxicities [grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations and grade 3 malaise]. The MTD in patients with HCC (Child-Pugh class A) was 600 mg QD. Diarrhea, skin hypopigmentation, and AST elevation were the most commonly reported adverse events at the MTD. Mean C max and area under the concentration-time curve (AUC 0-6) of pazopanib and its metabolites did not increase dose proportionally across the 200 to 800 mg range. Reductions in IAUGC and K trans were shown at all pazopanib doses evaluated, with the greatest reductions at 600 and 800 mg. Although larger DCE-MRI parameter decreases were associated with larger C 24 and C max values, there was no constant relationship between tumor perfusion decreases measured by DCE-MRI and plasma pazopanib pharmacokinetic parameters. Overall, 19 patients (73%) had either partial response or stable disease. Conclusion: Pazopanib has a manageable safety profile in patients with advanced HCC, and 600 mg was chosen for further development of pazopanib in advanced HCCs. Moreover, pazopanib reduced tumor vessel leakage, as shown by DCE-MRI, indicating a direct effect on HCC vasculature that might be associated with its antitumor activity. ©2011 AACR.link_to_subscribed_fulltex