Wild Ducks as Long-Distance Vectors of Highly Pathogenic Avian Influenza Virus (H5N1)

Some duck species are potential long-distance vectors; others are more likely to function as sentinels

An exploratory qualitative assessment of factors influencing childhood vaccine providers' intention to recommend immunization in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Under the Dutch national immunization program (NIP), childhood vaccination is not mandatory, but its recommendation by childhood vaccine providers (CVP) is important for maintaining high vaccination coverage. We therefore examined factors related to providers' intentions to recommend vaccinations to parents of young children.</p> <p>Methods</p> <p>We conducted four focus group discussions with nurses and physicians who provide vaccines to children 0-4 years old in diverse regions of the Netherlands. Three groups represented CVPs at child welfare centers (CWCs) serving the general population, with the fourth representing anthroposophical CWCs. Elements of the Theory of Planned Behaviour (TPB) were used to design the groups; thematic analysis was used to structure and analyze the dataset.</p> <p>Results</p> <p>Four main themes emerged, including 1) perceived responsibility: to promote vaccines and discuss pros and cons with parents (although this was usually not done if parents readily accepted the vaccination); 2) attitudes toward the NIP: mainly positive, but doubts as to NIP plans to vaccinate against diseases with a low perceived burden; 3) organizational factors: limited time and information can hamper discussions with parents; 4) relationship with parents: crucial and based mainly on communication to establish trust. Compared to CVPs at standard CWCs, the anthroposophical CWCs spent more time communicating and were more willing to adapt the NIP to individual cases.</p> <p>Conclusions</p> <p>Our qualitative assessment provides an overview of beliefs associated with providers' intention to recommend vaccinations. They were motivated to support the NIP, but their intentions to recommend vaccinations were affected by the perceived relevance of the vaccines, practical issues like limited time and by certain types of resistant parents. These results will inform future studies to test the magnitude and relative impact of these factors.</p

Improving the cost-effectiveness of cardiovascular disease prevention in Australia : a modelling study

Background : Cardiovascular disease is the leading cause of death worldwide. Like many countries, Australia is currently changing its guidelines for cardiovascular disease prevention from drug treatment for everyone with \u27high blood pressure\u27 or \u27high cholesterol\u27, to prevention based on a patient\u27s absolute risk. In this research, we model cost-effectiveness of cardiovascular disease prevention with blood pressure and lipid drugs in Australia under three different scenarios: (1) the true current practice in Australia; (2) prevention as intended under the current guidelines; and (3) prevention according to proposed absolute risk levels. We consider the implications of changing to absolute risk-based cardiovascular disease prevention, for the health of the Australian people and for Government health sector expenditure over the long term. Methods : We evaluate cost-effectiveness of statins, diuretics, ACE inhibitors, calcium channel blockers and beta-blockers, for Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Epidemiological changes and health care costs are simulated by age and sex in a discrete time Markov model, to determine total impacts on population health and health sector costs over the lifetime, from which we derive cost-effectiveness ratios in 2008 Australian dollars per quality-adjusted life year. Results : Cardiovascular disease prevention based on absolute risk is more cost-effective than prevention under the current guidelines based on single risk factor thresholds, and is more cost-effective than the current practice, which does not follow current clinical guidelines. Recommending blood pressure-lowering drugs to everyone with at least 5% absolute risk and statin drugs to everyone with at least 10% absolute risk, can achieve current levels of population health, while saving $5.4 billion for the Australian Government over the lifetime of the population. But savings could be as high as$7.1 billion if Australia could match the cheaper price of statin drugs in New Zealand. Conclusions : Changing to absolute risk-based cardiovascular disease prevention is highly recommended for reducing health sector spending, but the Australian Government must also consider measures to reduce the cost of statin drugs, over and above the legislated price cuts of November 2010. <br /

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

Genotyp-spezifische Peptide im Harn als molekulare Grundlage für die olfaktorische Erkennung der Individualität und des genetischen Verwandtschaftsgrades bei Mäusen

The degree of genomic relatedness influences many social behaviours in humans and animals. Mice, as nocturnal rodents, take advantage of their excellent sense of smell to identify kin, conspecifics and members of other species via body odours or urine scent marks. Selected groups of peptides, including those that are presented by major histocompatibility complex (MHC) proteins, are recognised by mouse chemosensory neurons with very high sensitivity (up to 10^-14 M). MHC peptide ligands have been proposed to influence social interactions in many species, including mice and humans. However, the lack of knowledge about such peptides in natural sources accessible for nasal recognition has been a major barrier for this hypothesis. Here we analyse urinary peptides from selected inbred strains of Mus musculus with respect to genotype-related differences. We discover many abundant peptides with single amino acid variations (SAVs) corresponding to genomic nucleotide variations. The polymorphism of major urinary proteins (MUPs) is reflected by variations in prominent urinary peptides, and further types of genomic variability are predicted to affect the urinary peptidome. Several peptides with MHC binding motifs are readily detectable in urine at concentrations of up to 10^-6 M, but their occurrence is independent of the MHC. On the other hand, by comparing mouse strains expressing chicken ovalbumin together with, or without, functional MHC class I molecules, we provide conclusive evidence that the prototypic H2-Kb ligand SIINFEKL (derived from ovalbumin) exists in urine at a concentration of 4 x 10^-12 M in an MHC-dependent manner. In cooperation with neurobiologists, we show that chemoreceptive neurons in the vomeronasal organ detect and discriminate SAV peptides as well as SIINFEKL. The present thesis fills a critical gap in the hypothesis that MHC peptide ligands may serve as signals of individuality in mice by providing the first evidence for such a ligand occurring in urine in an MHC-dependent manner. However, at the same time, this study profoundly questions the same hypothesis by showing, first, that the respective peptide concentrations in urine are about eight orders of magnitude lower than those previously applied in behavioural experiments and second, by demonstrating abundant MHC-independent MHC motif peptides. I therefore suppose that the copious peptides which reflect genomic individuality independent of MHC genes are far more important in determining social behaviours than the MHC-dependent ones. Collectively, urinary peptides represent a real-time sampling of the expressed genome available for chemosensory assessment by other individuals.Der genetische Verwandtschaftsgrad wirkt sich auf viele soziale Verhaltensweisen von Mensch und Tier aus. Als nachtaktive Nagetiere nutzen Mäuse ihren hervorragenden Geruchsinn, um Familienangehörige, Artgenossen und Vertreter fremder Arten zu identifizieren. Die benötigten Informationen können sie dabei auch aus Urinduftmarken gewinnen. Chemosensorische Nervenzellen der Maus erkennen bestimmte Peptidsorten, einschließlich denjenigen, die von den Proteinen des Haupthistokompatibilitätskomplexes (major histocompatibility complex, MHC) präsentiert werden, mit sehr hohen Sensitivitäten von bis zu 10^-14 M. Es wurde postuliert, dass MHC-Peptidliganden soziale Beziehungen bei vielen verschiedenen Arten, einschließlich Maus und Mensch, beeinflussen. Ein grundlegendes Problem bei dieser Hypothese ist jedoch das fehlende Wissen über solche Peptide in Duftquellen, die natürlicherweise für die Geruchserkennung zur Verfügung stehen. Hier untersuchen wir Urinpeptide von ausgewählten Inzuchtstämmen von Mus musculus in Bezug auf Unterschiede, die mit dem Genotyp zusammenhängen. Dabei entdecken wir viele häufige Peptide mit Einzelaminosäurevariationen (EAVs), welche genomischen Nukleotidvariationen entsprechen. Der Polymorphismus der Major Urinary Proteine (MUPs) spiegelt sich in Unterschieden in prominenten Urinpeptiden wider, und es kann vorhergesagt werden, dass weitere Arten genomischer Vielfalt das Urinpeptidom beeinflussen. Mehrere Peptide mit MHC-Bindemotiven sind im Harn in Konzentrationen von kleiner-gleich 10^-6 M leicht nachzuweisen, treten aber unabhängig vom MHC auf. Andererseits können wir einen schlüssigen Nachweis liefern, dass der prototypische H2-Kb-Ligand SIINFEKL, welcher aus Hühner-Ovalbumin stammt, MHC-abhängig mit einer Konzentration von 4 x 10^-12 M im Harn Ovalbumin-transgener Mäuse vorkommt. Der Nachweis der MHC-Abhängigkeit erfolgt dabei unter Nutzung eines Mausstammes, der Ovalbumin, aber keine funktionellen MHC-Klasse-I-Moleküle exprimiert. In Zusammenarbeit mit Neurobiologen zeigen wir, dass chemosensorische Nervenzellen im Vomeronasalorgan sowohl EAV-Peptide als auch SIINFEKL erkennen und unterscheiden können. Die vorliegende Doktorarbeit schließt eine entscheidende Lücke in der Hypothese, dass MHC-Peptidliganden als Signale der Individualität von Mäusen dienen können, indem sie den ersten Nachweis für einen solchen Liganden erbringt, der MHC-abhängig im Harn auftritt. Gleichzeitig stellt unsere Studie dieselbe Hypothese jedoch grundlegend in Frage, weil sie erstens zeigt, dass die entsprechenden Peptidkonzentrationen im Urin etwa acht Größenordnungen unter denjenigen liegen, welche in vorangegangenen Verhaltensexperimenten verwendet wurden und weil sie zweitens häufige MHC-unabhängige MHC-Motivpeptide nachweist. Ich vermute daher, dass die zahlreichen Peptide, welche die genomische Individualität unabhängig von MHC-Genen widerspiegeln, für das Sozialverhalten weitaus wichtiger sind als die MHC-abhängigen. In ihrer Gesamtheit bilden Urinpeptide Teile des exprimierten Genoms in Echtzeit ab und machen es somit für die chemosensorische Analyse durch andere Individuen zugänglich

Of volatiles and peptides: in search for MHC-dependent olfactory signals in social communication

Genes of the major histocompatibility complex (MHC), which play a critical role in immune recognition, are considered to influence social behaviors in mice, fish, humans, and other vertebrates via olfactory cues. As studied most extensively in mice, the polymorphism of MHC class I genes is considered to bring about a specific scent signature, which is decoded by the olfactory system resulting in an individual-specific reaction such as mating. On the assumption that this signature resides in volatiles, extensive attempts to identify these MHC-specific components in urine failed. Alternatively, it has been suggested that peptide ligands of MHC class I molecules are released into urine and can elicit an MHC-haplotype-specific behavioral response after uptake into the nose by sniffing. Analysis of the urinary peptide composition of mice shows that MHC-derived peptides are present, albeit in extremely low concentrations. In contrast, urine contains abundant peptides which differ between mouse strains due to genomic variations such as single-nucleotide variations or complex polymorphisms in multigene families as well as in their concentration. Thus, urinary peptides represent a real-time sampling of the expressed genome available for sensory evaluation. It is suggested that peptide variation caused by genomic differences contains sufficient information for individual recognition beyond or instead of an influence of the MHC in mice and other vertebrates