Ethics of a partially effective dengue vaccine: Lessons from the Philippines

Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent.Marie Skłodowska-Curie grant agreement No 79249

Why consumers drink natural wine? Consumer perception and information about natural wine

Similar to other foods, the concept of natural wine is much debated due to the lack of a clear and regulated definition, leading to a proliferation of heterogeneous norms and standards proposed from different natural wine associations at national levels. The current study explored the aspects which mediate individuals’ information and perception of natural wine, and the rationale behind natural wine consumption behavior among Italian (n = 501) and Spanish (n = 527) regular wine consumers. The results reveal a quite low self-reported degree of perceived information by Italian respondents and slightly higher levels among Spanish ones. The key drivers of natural wine consumption in both countries are wine consumption frequency, information, and natural product interest. In contrast, higher wine involvement levels decrease natural wine consumption frequency in both Italy and Spain. The findings also show that different perceptions lead to diverse motivations, suggesting the need for more homogeneous standards to mitigate the level of information asymmetry currently on the market

GRADE equity guidelines 3: considering health equity in GRADE guideline development: rating the certainty of synthesized evidence

Objectives: The aim of this paper is to describe a conceptual framework for how to consider health equity in the Grading Recommendations Assessment and Development Evidence (GRADE) guideline development process. Study Design and Setting: Consensus-based guidance developed by the GRADE working group members and other methodologists. Results: We developed consensus-based guidance to help address health equity when rating the certainty of synthesized evidence (i.e., quality of evidence). When health inequity is determined to be a concern by stakeholders, we propose five methods for explicitly assessing health equity: (1) include health equity as an outcome; (2) consider patient-important outcomes relevant to health equity; (3) assess differences in the relative effect size of the treatment; (4) assess differences in baseline risk and the differing impacts on absolute effects; and (5) assess indirectness of evidence to disadvantaged populations and/or settings. Conclusion: The most important priority for research on health inequity and guidelines is to identify and document examples where health equity has been considered explicitly in guidelines. Although there is a weak scientific evidence base for assessing health equity, this should not discourage the explicit consideration of how guidelines and recommendations affect the most vulnerable members of society

EGF-R signaling through Fyn kinase disrupts the function of integrin α6β4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion

We have examined the mechanism and functional significance of hemidesmosome disassembly during normal epithelial cell migration and squamous carcinoma invasion. Our findings indicate that a fraction of EGF receptor (EGF-R) combines with the hemidesmosomal integrin α6β4 in both normal and neoplastic keratinocytes. Activation of the EGF-R causes tyrosine phosphorylation of the β4 cytoplasmic domain and disruption of hemidesmosomes. The Src family kinase inhibitors PP1 and PP2 prevent tyrosine phosphorylation of β4 and disassembly of hemidesmosomes without interfering with the activation of EGF-R. Coimmunoprecipitation experiments indicate that Fyn and, to a lesser extent, Yes combine with α6β4. By contrast, Src and Lck do not associate with α6β4 to a significant extent. A dominant negative form of Fyn, but not Src, prevents tyrosine phosphorylation of β4 and disassembly of hemidesmosomes. These observations suggest that the EGF-R causes disassembly of hemidesmosomes by activating Fyn, which in turn phosphorylates the β4 cytoplasmic domain. Neoplastic cells expressing dominant negative Fyn display increased hemidesmosomes and migrate poorly in vitro in response to EGF. Furthermore, dominant negative Fyn decreases the ability of squamous carcinoma cells to invade through Matrigel in vitro and to form lung metastases following intravenous injection in nude mice. These results suggest that disruption of hemidesmosomes mediated by Fyn is a prerequisite for normal keratinocyte migration and squamous carcinoma invasion

Assessment of Bias in Pan-Tropical Biomass Predictions

Above-ground biomass (AGB) is an essential descriptor of forests, of use in ecological and climate-related research. At tree- and stand-scale, destructive but direct measurements of AGB are replaced with predictions from allometric models characterizing the correlational relationship between AGB, and predictor variables including stem diameter, tree height and wood density. These models are constructed from harvested calibration data, usually via linear regression. Here, we assess systematic error in out-of-sample predictions of AGB introduced during measurement, compilation and modeling of in-sample calibration data. Various conventional bivariate and multivariate models are constructed from open access data of tropical forests. Metadata analysis, fit diagnostics and cross-validation results suggest several model misspecifications: chiefly, unaccounted for inconsistent measurement error in predictor variables between in- and out-of-sample data. Simulations demonstrate conservative inconsistencies can introduce significant bias into tree- and stand-scale AGB predictions. When tree height and wood density are included as predictors, models should be modified to correct for bias. Finally, we explore a fundamental assumption of conventional allometry, that model parameters are independent of tree size. That is, the same model can provide predictions of consistent trueness irrespective of size-class. Most observations in current calibration datasets are from smaller trees, meaning the existence of a size dependency would bias predictions for larger trees. We determine that detecting the absence or presence of a size dependency is currently prevented by model misspecifications and calibration data imbalances. We call for the collection of additional harvest data, specifically under-represented larger trees

Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

PMCID: PMC3570554This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Estado poblacional del almendro como indicador de la disponibilidad de hábitat de Lapa verde en el sureste de Nicaragua

La investigación se realizó en siete comunidades del Sureste de Nicaragua, con el objetivo de determinar el estado actual de la población de almendro (Dipteryx panamensis), como indicador del hábitat potencial para la lapa verde (Ara ambiguus). Se muestrearon 21 parcelas de 1ha cada una, estableciendo tres parcelas por comunidad, también se entrevistaron a pobladores para determinar la relación de éstos con las especies en estudio. En las parcelas muestreadas, se contabilizaron un total de 93 árboles de almendro con Diámetro a la Altura del Pecho (DAP’s) ≥70cm, lo que representa una densidad promedio de 4.4 almendros/ha. También, se identificaron posibles amenazas para las especies en estudio y su particularidad con las comunidades y grupos étnicos. Resultados de Modelos Lineales Generalizados (GLM) y análisis de correlación, indican que en la zona de estudio, no es el tamaño o diámetro de los almendros lo que mantiene poblaciones de lapas, sino que influyen mucho la densidad de individuos con DAP≥70cm, el nivel de aislamiento de la comunidad, y la cantidad y tipo de usos que le dan los pobladores al árbol. Desde los modelos de Maxent, en los alrededores de 5 comunidades (La Bijagua, Bartola, Indian River, Corn River y Point of Rock) presentan condiciones viables para la distribución del hábitat potencial del almendro y por ende de lapas verdes

Estado poblacional del Almendro como indicador de la disponibilidad de hábitat de Lapa Verde en el Sureste de Nicaragua

La investigación se realizó en siete comunidades del Sureste de Nicaragua, con el objetivo de determinar el estado actual de la población de almendro (Dipteryx panamensis), como indicador del hábitat potencial para la lapa verde (Ara ambiguus). Se muestrearon 21 parcelas de 1ha cada una, estableciendo tres parcelas por comunidad, también se entrevistaron a pobladores para determinar la relación de éstos con las especies en estudio. En las parcelas muestreadas, se contabilizaron un total de 93 árboles de almendro con Diámetro a la Altura del Pecho (DAP’s) ≥70cm, lo que representa una densidad promedio de 4.4 almendros/ha. También, se identificaron posibles amenazas para las especies en estudio y su particularidad con las comunidades y grupos étnicos. Resultados de Modelos Lineales Generalizados (GLM) y análisis de correlación, indican que en la zona de estudio, no es el tamaño o diámetro de los almendros lo que mantiene poblaciones de lapas, sino que influyen mucho la densidad de individuos con DAP≥70cm, el nivel de aislamiento de la comunidad y la cantidad y tipo de usos que le dan los pobladores al árbol. Desde los modelos de Maxent, en los alrededores de 5 comunidades (La Bijagua, Bartola, Indian River, Corn River y Point of Rock) presentan condiciones viables para la distribución del hábitat potencial del almendro y por ende de lapas verdes.SummaryThe research was done in seven communities in the southeast of Nicaragua, in order to determine the current condition of almond-tree population (Dipteryx panamensis), as an indicator of potential habitat for the Green Macaw (Ara ambiguus). 21 plots of 1ha each were sampled, by establishing three plots per community. Community people were also interviewed to determine their relationship with the species object of study. In the sampled plots, a total of 93 almond-trees were counted with Diameter at Breast Height (DBH's) ≥70cm, representing an average density of 4.4 almond-trees/ha. Potential threats were also identified to the species subject of study and its particularity with the communities and ethnic groups.The results of Generalized Linear Models (GLM) and the analysis of correlation, indicate that in the study area, it is not the size or diameter of the almond trees that maintains the green macaws populations, but what influences much is the density of individuals with DAP≥70cm, the level of isolation of the community and the amount and type of uses that the community people gives to the tree. According to Maxent models, on the surroundings of 5 communities (La Bijagua, Bartolo, Indian River, Corn River and Point of Rock) it offers viable conditions for the distribution of potential habitat for almond-tree and thus, for green macaws

Organizational perceptions of e-commerce: Re-assessing the benefits

This paper reports on preliminary findings from a wider and more in-depth study of six traditional organizations from different sectors that have successfully introduced e-commerce initiatives. The research adopted a case study approach, within which a questionnaire, identifying 16 generic benefits synthesized from the literature, was administered. The organizations were also asked to characterize whether e-commerce was strategic for them or not. The findings suggest that those organizations that perceived e-commerce to be strategic tended to consider intangible benefits as more important than tangible benefits, indicating perhaps a move away from the traditional view of e-commerce as a marketing driver to increase or create sales. Those organizations perceiving e-commerce as non-strategic rated the tangible benefits in much the same way as the strategic organizations, but rated the intangibles lower. Also it was found that e-commerce was important as a communication tool, not only with customers, as might be expected, but also with staff within the organization. The value of intra-organizational e-commerce was also found to be important, perhaps more than previously thought, as was its use in communicating and disseminating knowledge. The findings also reflect the importance of the sector and environment of the organization in determining their perceptions of e-commerce