Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza

The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 µg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 µg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations.ClinicalTrials.gov NCT00984945

A framework for the prospective analysis of ethno-cultural super-diversity

Background: Pressures to keep immigration rates at relatively high levels are likely to persist in most developed countries. At the same time, immigrant cohorts are becoming more and more diverse, leading host societies to become increasingly heterogeneous across multiple dimensions. For scholars who study demographic or socio-economic behaviours, the need to account for ethno-cultural “super-diversity” brings new challenges. Objective: The main objective of this paper is to present a framework for the prospective analysis of super-diversity in several high immigration countries. Methods: We developed microsimulation models that simultaneously project several population dimensions for Canada, the United States and countries of the European Union, with the aim of studying the consequences of alternate future population and migration trends. Results: The paper presents the projected progression of three indicators of diversity: percentage of foreign-born population, percentage of the population using a non-official language at home and percentage of non-Christians. It also examines the projected changes in the labour force by education levels and language. Using alternative scenarios, we also show that the proportion of highly educated in the US and EU28 labour force could increase by 11 and 15 percentage points respectively if future immigrants were selected as in Canada. Finally, the paper proposes a new longitudinal indicator that counts the number of years lived as active and inactive over the life course for foreign- and native-born cohorts. Contribution: The microsimulation models provide much more informative results than more traditional cohort-component models to study the future effects of ethno-cultural super-diversity on high immigration countries

Ambient temperature does not affect fuelling rate in absence of digestive constraints in long-distance migrant shorebird fuelling up in captivity

Pre-flight fuelling rates in free-living red knots Calidris canutus, a specialized long-distance migrating shorebird species, are positively correlated with latitude and negatively with temperature. The single published hypothesis to explain these relationships is the heat load hypothesis that states that in warm climates red knots may overheat during fuelling. To limit endogenous heat production (measurable as basal metabolic rate BMR), birds would minimize the growth of digestive organs at a time they need. This hypothesis makes the implicit assumption that BMR is mainly driven by digestive organ size variation during pre-flight fuelling. To test the validity of this assumption, we fed captive knots with trout pellet food, a diet previously shown to quickly lead to atrophied digestive organs, during a fuelling episode. Birds were exposed to two thermal treatments (6 and 24°C) previously shown to generate different fuelling rates in knots. We made two predictions. First, easily digested trout pellet food rather than hard-shelled prey removes the heat contribution of the gut and would therefore eliminate an ambient temperature effect on fuelling rate. Second, if digestive organs were the main contributors to variations in BMR but did not change in size during fuelling, we would expect no or little change in BMR in birds fed ad libitum with trout pellets. We show that cold-acclimated birds maintained higher body mass and food intake (8 and 51%) than warm-acclimated birds. Air temperature had no effect on fuelling rate, timing of fuelling, timing of peak body mass or BMR. During fuelling, average body mass increased by 32% while average BMR increased by 15% at peak of mass and 26% by the end of the experiment. Our results show that the small digestive organs characteristic of a trout pellet diet did not prevent BMR from increasing during premigratory fuelling. Our results are not consistent with the heat load hypothesis as currently formulated

DMSP synthesis and exudation in phytoplankton:a modeling approach

In the marine environment, phytoplankton are the fundamental producers of dimethylsulfoniopropionate (DMSP), the precursor of the climatically active gas dimethylsulfide (DMS). DMSP is released by exudation, cell autolysis, and zooplankton grazing during phytoplankton blooms. In this study, we developed a model of phytoplankton DMSP and DMS production allowing quantification of the exudation rates of these compounds during different growth phases. The model was tested on published data from axenic cultures of Prorocentrum minimum and Phaeocystis sp.; DMSP exudation rates vary considerably between the 2 species. Model results show that P. minimum exudes around 1% d(-1) of its DMSP quota during the latent, exponential and senescent phases. This is comparable to the average exudation rate estimated from previous laboratory experiments. However, Phaeocystis sp. exudes from 3 to 11% d(-1) of its DMSP quota. For this species, DMSP exudation rates apparently show an inverse relationship with the population growth rate. The maximum DMSP exudation rate in Phaeocystis sp. is 10 times higher than previously reported DMSP or DMS exudation rates. Our results suggest that exudation may be as important as cell autolysis in the release of DMSP during Phaeocystis sp. blooms. We conclude that exudation should be incorporated in models of DMS cycling in the marine environment. Moreover, our results for Phaeocystis sp. suggest that a low and constant exudation rate, as sometimes used in models, is not suitable for all conditions

Season of birth and Alzheimer's disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project)

The birth distribution of 399 cases of Alzheimer's disease (AD) identified in the region of Saguenay-Lac-St-Jean (Québec) was compared with that of: (a) the population currently living in the area; and (b) the population born during the same period in the area. AD cases have been recruited since 1986 by the IMAGE Project. Cases and controls were grouped according to the month of birth and according to the day of birth using density estimation. Analyses showed a significant deficit of births in the month of May. We believe these preliminary results deserve further attention and we suggest two possible explanations that could lead to a deficit of AD births at specific periods during the year

Suspensions cellulaires embryogènes de bananiers et bananiers plantain

This guideline presents two protocols to produce embryogenic cell suspensions by using scalps or immature male flowers. The protocols have been developed by the Laboratory of Tropical Crop Improvement of Katholieke Universiteit Leuven (KULeuven) and the cellular biology laboratory of the Centre de coopération internationale en recherche agronomique pour le développement (Cirad)

Banana and plantain embryogenic cell suspensions

This guideline presents two protocols to produce embryogenic cell suspensions by using scalps or immature male flowers. The protocols have been developed by the Laboratory of Tropical Crop Improvement of Katholieke Universiteit Leuven (KULeuven) and the cellular biology laboratory of the Centre de coopération internationale en recherche agronomique pour le développement (Cirad)

Suspensiones de células embriogénicas de banano y plátano

This guideline presents two protocols to produce embryogenic cell suspensions by using scalps or immature male flowers. The protocols have been developed by the Laboratory of Tropical Crop Improvement of Katholieke Universiteit Leuven (KULeuven) and the cellular biology laboratory of the Centre de coopération internationale en recherche agronomique pour le développement (Cirad)

Child sexual abuse by different classes and types of perpetrator: prevalence and trends from an Australian national survey

Background Little evidence exists about the prevalence of child sexual abuse (CSA) inflicted by different relational classes of perpetrators (e.g., parents; institutional adults; adolescents), and by individual types of perpetrators (e.g., fathers and male relatives; male teachers and male clergy; known and unknown adolescents). Objective To generate evidence of the prevalence of CSA by different perpetrators, and trends by victim gender and age group. Participants and setting The Australian Child Maltreatment Study collected information about CSA victimisation from a nationally-representative sample of 8503 individuals aged 16 and over. Methods We analysed data about 42 perpetrator types, collapsed into eight classes. We generated national prevalence estimates of CSA inflicted by each perpetrator class and individual perpetrator type, and compared results by victim gender and age group. Results Australian CSA prevalence was 28.5%, with the following prevalence by perpetrator classes: other known adolescents (non-romantic): 10.0%; parents/caregivers in the home: 7.8%; other known adults: 7.5%; unknown adults: 4.9%; adolescents (current/former romantic partners): 2.5%; institutional caregivers: 2.0%; siblings: 1.6%; unknown adolescents: 1.4%. Women experienced more CSA by all perpetrator classes except institutional caregivers. Age group comparison showed significant declines in CSA by parents/caregivers, and other known adults; and increases in CSA by adolescents (current/former romantic partners). Individual perpetrator type comparison showed declines in CSA by fathers, male relatives living in the home, non-resident male relatives, and other known male adults; and increases in CSA by known male adolescents, current boyfriends, and former boyfriends. Conclusions CSA by adults has declined, indicating positive impacts of prevention efforts. However, CSA by adolescents has increased. Further declines in CSA by adults are required and possible. Targeted prevention of CSA by adolescents must be prioritised

Knowledge, experience, and potential risks of dating violence among Japanese university students: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The Domestic Violence Prevention Act came into effect in Japan in 2001, but covers only marriage partner violence and post-divorce partner violence, and does not recognize intimate partner violence (IPV). The present study was performed to determine the experience of harassment, both toward and from an intimate partner, and recognition of harassment as IPV among Japanese university students.</p> <p>Methods</p> <p>A self-administered questionnaire survey regarding the experience of harassment involving an intimate partner was conducted as a cross-sectional study among freshman students in a prefectural capital city in Japan.</p> <p>Results</p> <p>A total of 274 students participated in the present study. About half of the subjects (both male and female students) had experience of at least one episode of harassment toward or had been the recipient of harassment from an intimate partner. However, the study participants did not recognize verbal harassment, controlling activities of an intimate partner, and unprotected sexual intercourse as violence. Experience of attending a lecture/seminar about domestic violence and dating violence did not contribute to appropriate help-seeking behavior.</p> <p>Conclusions</p> <p>An educational program regarding harassment and violence prevention and appropriate help-seeking behavior should be provided in early adolescence to avoid IPV among youth.</p