The Effectiveness of Preventative Mass Vaccination Regimes Against the Incidence of Highly Pathogenic Avian Influenza on Java Island,Indonesia

We conducted an operational research study involving backyard and semicommercial farms on Java Island, Indonesia, between April 2008 and September 2009 to evaluate the effectiveness of two preventive mass vaccination strategies against highly pathogenic avian influenza (HPAI). One regimen used Legok 2003 H5N1 vaccine, while the other used both Legok 2003 H5N1 and HB1 Newcastle disease (ND) vaccine. A total of 16 districts were involved in the study. The sample size was estimated using a formal power calculation technique that assumed a detectable effect of treatment as a 50% reduction in the baseline number of HPAI‐compatible outbreaks. Within each district, candidate treatment blocks with village poultry populations ranging from 80 000 to 120 000 were created along subdistrict boundary lines. Subsequently, four of these blocks were randomly selected and assigned one treatment from a list that comprised control, vaccination against HPAI, vaccination against HPAI + ND. Four rounds of vaccination were administered at quarterly intervals beginning in July 2008. A vaccination campaign involved vaccinating 100 000 birds in a treatment block, followed by another 100 000 vaccinations 3 weeks later as a booster dose. Data on disease incidence and vaccination coverage were also collected at quarterly intervals using participatory epidemiological techniques. Compared with the unvaccinated (control) group, the incidence of HPAI‐compatible events declined by 32% (P = 0.24) in the HPAI‐vaccinated group and by 73% (P = 0.00) in the HPAI‐ and ND‐vaccinated group. The effect of treatment did not vary with time or district. Similarly, an analysis of secondary data from the participatory disease and response (PDSR) database revealed that the incidence of HPAI declined by 12% in the HPAI‐vaccinated group and by 24% in the HPAI + ND‐vaccinated group. The results suggest that the HPAI + ND vaccination significantly reduced the incidence of HPAI‐compatible events in mixed populations of semicommercial and backyard poultry.     

Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients‘ perspective

Pituitary - While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient...     

AT2 Receptor and Tissue Injury: Therapeutic Implications

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of “agents of choice” across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.     

Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T‐cell cross‐priming

Toll‐like receptor (TLR) ligands are attractive candidate adjuvants for therapeutic cancer vaccines, since TLR signaling stimulates and tunes both humoral and cellular immune responses induced by dendritic cells (DCs). Given that human skin contains a dense network of DCs, which are easily accessible via (intra‐)dermal delivery of vaccines, skin is actively explored as an antitumor vaccination site. Here we used a human skin explant model to explore the potential of TLR ligands as adjuvants for DC activation in their complex microenvironment. We show that topical application of Aldara skin cream, 5% of which comprises the TLR7 agonist imiquimod, significantly enhanced DC migration as compared with that resulting from intradermal injection of the TLR7/8 ligand R848 or the soluble form of imiquimod. Moreover, Aldara‐treated DCs showed highest levels of the costimulatory molecules CD86, CD83, CD40, and CD70. Topical Aldara induced the highest production of pro‐inflammatory cytokines in skin biopsies. When combined with intradermal peptide vaccination, Aldara‐stimulated DCs showed enhanced cross‐presentation of the melanoma antigen MART‐1, which resulted in increased priming and activation of MART‐1‐specific CD8⁺ T cells. These results point to advantageous effects of combining the topical application of Aldara with antitumor peptide vaccination.     

Diffusion and Interface Effects during Preparation of All-Solid Microstructured Fibers

All-solid microstructured optical fibers (MOF) allow the realization of very flexible optical waveguide designs. They are prepared by stacking of doped silica rods or canes in complex arrangements. Typical dopants in silica matrices are germanium and phosphorus to increase the refractive index (RI), or boron and fluorine to decrease the RI. However, the direct interface contact of stacking elements often causes interrelated chemical reactions or evaporation during thermal processing. The obtained fiber structures after the final drawing step thus tend to deviate from the targeted structure risking degrading their favored optical functionality. Dopant profiles and design parameters (e.g., the RI homogeneity of the cladding) are controlled by the combination of diffusion and equilibrium conditions of evaporation reactions. We show simulation results of diffusion and thermal dissociation in germanium and fluorine doped silica rod arrangements according to the monitored geometrical disturbances in stretched canes or drawn fibers. The paper indicates geometrical limits of dopant structures in sub-µm-level depending on the dopant concentration and the thermal conditions during the drawing process. The presented results thus enable an optimized planning of the preform parameters avoiding unwanted alterations in dopant concentration profiles or in design parameters encountered during the drawing process.