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Background and Methods Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. Results The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. Conclusion Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate. Trial Registration ClinicalTrials.gov NCT00868218

1. Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right-to-left shunting. 2. Endothelins (ETs) are potent vasoconstrictors and pro-mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ET(A) receptors (ET(A)-Rs). 3. Evaluation of the effect of ABT-627, a selective non-peptidic ET(A)-R antagonist, given from -15 to 210 min post-delivery (1 mg kg(-1) bolus +0.01 mg kg(-1) h(-1) infusion, i.v.), was conducted in the lamb model of CDH. 4. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P0.0001), lower mean blood pressure (MBP; P=0.0004), higher MPAP / MBP ratio (P0.0001), lower arterial pH (P0.0001), higher paCO(2) (P0.0001), lower paO(2) (P0.0001) and lower post-ductal pulsatile SaO(2) (P0.0001) than untreated controls. 5. Treated controls (n=7) showed a higher MPAP, lower MBP, higher MPAP/MBP ratio, lower arterial pH, higher paCO(2), lower paO(2), lower post-ductal pulsatile SaO(2) and lower plasmatic ir-ET ratios compared to untreated controls (P0.0001). 6. Treated CDH lambs (n=8) showed a higher MBP (P0.0001), lower MPAP / MBP ratio (P0.0001), higher arterial pH (P0.0001), lower paCO(2) (P0.0001), higher paO(2) (P=0.0228), higher post-ductal pulsatile SaO(2) (P=0.0016) and lower plasmatic ir-ET ratios (P=0.0247) when compared to untreated CDH lambs. 7. These observations revealed that, although acute perinatal treatment with a selective non-peptidic ET(A)-R antagonist had some adverse effects in controls, it attenuated the progressive cardiopulmonary deterioration that occurred after birth in CDH lambs.

Art education has the potential to change the world. How art changed worlds — mine and those of the people in my art classes — unfolds here through text, fonts and images. These words and images try to touch upon "the intangible benefits" Wilson (1994) of art education. Art education that opens to the search for personal meaning through the wow of engaged experience, extends the content of traditional art education and operates with an awareness of the art as therapy is art as journey work. Journey work invites students to trust their unique vision of the world and in so doing moves towards social change by questioning dominant power-over structures through fostering power-from-within. Reflecting on the voices of the women i interviewed, on my personal journals and on discussions with my colleagues and friends, i interrogated my own art education practice. An interview-based methodology using memories and art work as key points for reflection, reflective research offers an intimate understanding of a classroom through stories and memories of three participants, two students and myself as teacher. Our participation in an on-going dialogue of friendship before and after interviews gives resonance and depth to our discussions. Weaving together my students' stories, my own life story, and theory brings the personal into the academic. The analysis section seeks relationships between these personal stories and the culture in which we are embedded, and concludes the personal is more than political, it is ecological: what we do to ourselves, we do to the web; what we do to the web, we do to ourselves.