Geneva-Seattle collaboration in support of developing country vaccine manufacturing.

Vaccines were once produced almost exclusively by state-supported entities. While they remain essential tools for public health protection, the majority of the world's governments have allowed industry to assume responsibility for this function. This is significant because while the international harmonisation of quality assurance standards have effectively increased vaccine safety, they have also reduced the number of developing country vaccine producers, and Northern multinational pharmaceutical companies have shown little interest in offering the range of low-priced products needed in low and middle-income-country contexts. This article examines how public-private collaboration is relevant to contemporary efforts aimed at strengthening developing country manufacturers' capacity to produce high-quality, low-priced vaccines. Specifically, it casts light on the important and largely complimentary roles of the World Health Organization, The Bill and Melinda Gates Foundation, and the Seattle-based non-profit PATH, in this process. The take away message is that external support remains critical to ensuring that developing country vaccine manufacturers have the tools needed to produce for both domestic and global markets, and the United Nations supply chain, and collaboration at the public-private interface is driving organisational innovation focused on meeting these goals.

The relevance of the public-private partnership paradigm to the prevention of diet-associated non-communicable diseases in wealthy countries.

The public-private partnership (PPP) paradigm emerged as a form of global health governance in the mid-1990s to overcome state and market failures constraining access to essential medicines among populations with limited purchasing power in low- and middle-income countries. PPPs are now ubiquitous across the development spectrum. Yet while the narrative that the private sector must be engaged if complex health challenges are to be overcome is now dominant in development discourse, it does not yet appear to be shaping government approaches to addressing health inequalities within high-income welfare states such as Canada. This is significant as both the actions and inactions of firms factor heavily into why low-income Canadians face a disproportionate risk of developing diet-associated chronic diseases, such as type II diabetes. In the same ways PPPs have been an effective policy tool for strengthening public health in poor countries, this paper illuminates how the PPP model may have utility for mitigating poverty-associated food insecurity giving rise to diet-associated non-communicable diseases within the context of wealthy states.

Short interfering RNA-mediated knockdown of drosha and pasha in undifferentiated Meloidogyne incognita eggs leads to irregular growth and embryonic lethality.

Micro-(mi)RNAs play a pivotal role in the developmental regulation of plants and animals. We reasoned that disruption of normal heterochronic activity in differentiating Meloidogyne incognita eggs may lead to irregular development, lethality and by extension, represent a novel target for parasite control. On silencing the nuclear RNase III enzyme drosha, a critical effector of miRNA maturation in animals, we found a significant inhibition of normal development and hatching in short interfering (si)RNA-soaked M. incognita eggs. Developing juveniles presented with highly irregular tissue patterning within the egg, and we found that unlike our previous gene silencing efforts focused on FMRFamide (Phe-Met-Arg-Phe-NH(2))-like peptides (FLPs), there was no observable phenotypic recovery following removal of the environmental siRNA. Aberrant phenotypes were exacerbated over time, and drosha knockdown proved embryonically lethal. Subsequently, we identified and silenced the drosha cofactor pasha, revealing a comparable inhibition of normal embryonic development within the eggs to that of drosha-silenced eggs, eventually leading to embryonic lethality. To further probe the link between normal embryonic development and the M. incognita RNA interference (RNAi) pathway, we attempted to examine the impact of silencing the cytosolic RNase III enzyme dicer. Unexpectedly, we found a substantial up-regulation of dicer transcript abundance, which did not impact on egg differentiation or hatching rates. Silencing of the individual transcripts in hatched J2s was significantly less successful and resulted in temporary phenotypic aberration of the J2s, which recovered within 24h to normal movement and posture on washing out the siRNA. Soaking the J2s in dicer siRNA resulted in a modest decrease in dicer transcript abundance which had no observable impact on phenotype or behaviour within 48h of initial exposure to siRNA. We propose that drosha, pasha and their ancillary factors may represent excellent targets for novel nematicides and/or in planta controls aimed at M. incognita, and potentially other parasitic nematodes, through disruption of miRNA-directed developmental pathways. In addition, we have identified a putative Mi-eri-1 transcript which encodes an RNAi-inhibiting siRNA exonuclease. We observe a marked up-regulation of Mi-eri-1 transcript abundance in response to exogenously introduced siRNA, and reason that this may impact on the interpretation of RNAi-based reverse genetic screens in plant parasitic nematodes.

Use of xenon as a sedative for patients receiving critical care.

OBJECTIVE: Many sedative regimens are used in the intensive care setting, but none are wholly without adverse effect. Xenon is a noble gas with sedative and analgesic properties. It has been used successfully as a general anesthetic and has many desirable properties, not least of which is a minimal effect on the myocardium. In theory, xenon may provide sedation without adverse effect for certain groups of critically ill patients. The objective of this study was to assess the feasibility of using xenon as an intensive care sedative. DESIGN: Double-blind, randomized study. SETTING: Tertiary-level intensive care unit. SUBJECTS: Twenty-one patients admitted to an intensive care unit following elective thoracic surgery. INTERVENTIONS: A standard intensive care sedation regimen (intravenous propofol at 0-5 mg.kg-1.hr-1 and alfentanil 30 microg.kg-1.hr-1) was compared with a xenon sedation regimen delivered using a novel bellows-in-bottle delivery system. MEASUREMENTS AND MAIN RESULTS Each sedative regimen was continued for 8 hrs. The hemodynamic effects, additional analgesic requirements, recovery from sedation, and effect on hematological and biochemical variables were compared for the two sedation regimens. All patients were successfully sedated during the xenon regimen. The mean +/- SD end-tidal xenon concentration required to provide sedation throughout the duration of the study was 28 +/- 9.0% (range, 9-62%). Arterial systolic, diastolic, and mean pressures showed a greater tendency for negative gradients in patients receiving the propofol regimen (p <.05, p <.1, and p <.01, respectively). Recovery following xenon was significantly faster than from the standard sedation regimen (p <.0001). Hematological and biochemical laboratory markers were within normal clinical limits in both groups. CONCLUSIONS: Xenon provided satisfactory sedation in our group of patients. It was well tolerated with minimal hemodynamic effect. Recovery from this agent is extremely rapid. We have demonstrated the feasibility of using xenon within the critical care setting, without adverse effect.