Comparison of the Efficacy of Brolucizumab with Natural Disease Progression in Wet AMD Using Clinical Data from the Phase III HAWK and HARRIER Trials and Modelled Placebo Data

Aim: To compare the treatment effect of brolucizumab, a novel anti-vascular endothelial growth factor therapeutic, with a putative placebo in patients with wet age-related macular degeneration. Materials and Methods: Clinical treatment-effect data from patients receiving brolucizumab 6 mg in the HAWK and HARRIER studies were compared with modelled placebo data using a previously developed and validated indirect response, non-linear, mixed effects model describing the natural visual acuity decline in wet age-related macular degeneration. The placebo model incorporated patient-level data from the sham injection arms of the MARINA and PIER studies, corrected for baseline best corrected visual acuity and age difference between these studies and the HAWK and HARRIER studies. Results: Compared with a modelled placebo, brolucizumab treatment was associated with an overall best corrected visual acuity gain of approximately 22 Early Treatment Diabetic Retinopathy Study letters at Week 48 and 28 letters at Week 96. Conclusions: As anti-vascular endothelial growth factor therapy is now a standard of care for wet age-related macular degeneration, it is not feasible to conduct placebo-controlled trials for new wet age-related macular degeneration treatments. By allowing comparison with the natural decline in visual acuity without treatment, this analysis conveys the clinical importance of brolucizumab for the treatment of wet age-related macular degeneration

A new species of Colostethus (Anura, Dendrobatidae) from French Guiana with a redescription of Colostethus beebei (Noble, 1923) from its type locality

A new species of Colostethus, long mistaken for Colostethus beebei, is described from French Guiana. The new species can be distinguished from congeners by absence of median lingual process, first finger longer than second, third finger not distinctly swollen in males, differences in tadpole morphology, coloration and pattern (e.g. absence of dorsolateral stripe), bioacoustics, and reproductive behavior. A complete redescription of Colostethus beebei plus description of its tadpole and call is provided on the basis of recently collected topotypic specimens. The range of C. beebei is restricted to the Kaieteur plateau, Pakaraima Mountains, Guyana

Ordered structure of FeGe₂ formed during solid-phase epitaxy

Fe3Si/Ge(Fe,Si)/Fe3Si thin-film stacks were grown by a combination of molecular beam epitaxy and solid-phase epitaxy (Ge on Fe3Si). The stacks were analyzed using electron microscopy, electron diffraction, and synchrotron x-ray diffraction. The Ge(Fe,Si) films crystallize in the well-oriented, layered tetragonal structure FeGe2 with space group P4mm. This kind of structure does not exist as a bulk material and is stabilized by the solid-phase epitaxy of Ge on Fe3Si. We interpret this as an ordering phenomenon induced by minimization of the elastic energy of the epitaxial film

Implicating municipalities in addressing household food insecurity in Canada: A pan-Canadian analysis of news print media coverage

Objectives: Household food insecurity (HFI) affects approximately 13% of Canadian households and is especially prevalent among low-income households. Actions to address HFI have been occurring primarily at the local level, despite calls for greater income supports from senior governments to reduce poverty. News media may be reinforcing this trend, by emphasizing food-based solutions to HFI and the municipal level as the site where action needs to take place. The objective of this study was to examine the level and framing of print news media coverage of HFI action in Canada. Methods: Using a quantitative newspaper content analysis approach, we analyzed 547 articles gathered from 2 national and 16 local/regional Englishlanguage newspapers published between January 2007 and December 2012. Results: News coverage increased over time, and over half was produced from Ontario (33%) and British Columbia (22%) combined. Of the 374 articles that profiled a specific action, community gardens/urban agriculture was most commonly profiled (17%), followed by food banks/meal programs (13%); 70% of articles implicated governments to take action on HFI, and of these, 43% implicated municipal governments. Article tone was notably more negative when senior governments were profiled and more neutral and positive when municipal governments were profiled. Conclusion: News media reporting of this issue in Canada may be placing pressure on municipalities to engage in food-based actions to address HFI. A more systematic approach to HFI action in Canada will require more balanced media reporting that acknowledges the limitations of food-based solutions to the income-based problem of HFI

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed