Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery

Second best toll and capacity optimisation in network: solution algorithm and policy implications

This paper looks at the first and second-best jointly optimal toll and road capacity investment problems from both policy and technical oriented perspectives. On the technical side, the paper investigates the applicability of the constraint cutting algorithm for solving the second-best problem under elastic demand which is formulated as a bilevel programming problem. The approach is shown to perform well despite several problems encountered by our previous work in Shepherd and Sumalee (2004). The paper then applies the algorithm to a small sized network to investigate the policy implications of the first and second-best cases. This policy analysis demonstrates that the joint first best structure is to invest in the most direct routes while reducing capacities elsewhere. Whilst unrealistic this acts as a useful benchmark. The results also show that certain second best policies can achieve a high proportion of the first best benefits while in general generating a revenue surplus. We also show that unless costs of capacity are known to be low then second best tolls will be affected and so should be analysed in conjunction with investments in the network

Improvised Peritoneal Dialysis in an 18-month-old Child with Severe Acute Malnutrition (kwashiorkor) and Acute kidney Injury: A Case Report.

Severe acute malnutrition is common in developing countries. Children with severe acute malnutrition are prone to complications, including electrolyte imbalance and infections. Our patient was an 18-month-old boy who had severe acute malnutrition (kwashiorkor) and developed acute kidney injury, which was managed with peritoneal dialysis using improvised equipment. This case report illustrates the importance of improvisation in resource-limited settings in providing lifesaving treatment. To the best of our knowledge, this is the first case report on peritoneal dialysis in a child with severe acute malnutrition (kwashiorkor). We report a case of an 18-month-old Bantu-African Tanzanian boy who had severe malnutrition and developed anuric acute kidney injury. He had severe renal dysfunction and was managed with peritoneal dialysis using an improvised catheter and bedside constituted fluids (from intravenous fluids) and was diuretic after 7 days of peritoneal dialysis, with complete recovery of renal functions after 2 weeks. Children with severe acute malnutrition who develop acute kidney injury should be offered peritoneal dialysis, which may be provided using improvised equipment in resource-limited settings, as illustrated in this case report

Discovery of dipolar chromospheres in two white dwarfs

This paper reports the ULTRACAM discovery of dipolar surface spots in two cool magnetic white dwarfs with Balmer emission lines, while a third system exhibits a single spot, similar to the prototype GD 356. The light curves are modelled with simple, circular, isothermal dark spots, yielding relatively large regions with minimum angular radii of 20°. For those stars with two light-curve minima, the dual spots are likely observed at high inclination (or colatitude); however, identical and antipodal spots cannot simultaneously reproduce both the distinct minima depths and the phases of the light-curve maxima. The amplitudes of the multiband photometric variability reported here are all several times larger than that observed in the prototype GD 356; nevertheless, all DAHe stars with available data appear to have light-curve amplitudes that increase towards the blue in correlated ratios. This behaviour is consistent with cool spots that produce higher contrasts at shorter wavelengths, with remarkably similar spectral properties given the diversity of magnetic field strengths and rotation rates. These findings support the interpretation that some magnetic white dwarfs generate intrinsic chromospheres as they cool, and that no external source is responsible for the observed temperature inversion. Spectroscopic time-series data for DAHe stars is paramount for further characterization, where it is important to obtain well-sampled data, and consider wavelength shifts, equivalent widths, and spectropolarimetry

Enhanced thylakoid photoprotection can increase yield and canopy radiation use efficiency in rice

High sunlight can raise plant growth rates but can potentially cause cellular damage. The likelihood of deleterious effects is lowered by a sophisticated set of photoprotective mechanisms, one of the most important being the controlled dissipation of energy from chlorophyll within photosystem II (PSII) measured as non-photochemical quenching (NPQ). Although ubiquitous, the role of NPQ in plant productivity remains uncertain because it momentarily reduces the quantum efficiency of photosynthesis. Here we used plants overexpressing the gene encoding a central regulator of NPQ, the protein PsbS, within a major crop species (rice) to assess the effect of photoprotection at the whole canopy scale. We accounted for canopy light interception, to our knowledge for the first time in this context. We show that in comparison to wild-type plants, psbS overexpressors increased canopy radiation use efficiency and grain yield in fluctuating light, demonstrating that photoprotective mechanisms should be altered to improve rice crop productivity

Enteric Pathogens in Stored Drinking Water and on Caregiver's Hands in Tanzanian Households with and without Reported Cases of Child Diarrhea.

Diarrhea is one of the leading causes of mortality in young children. Diarrheal pathogens are transmitted via the fecal-oral route, and for children the majority of this transmission is thought to occur within the home. However, very few studies have documented enteric pathogens within households of low-income countries. The presence of molecular markers for three enteric viruses (enterovirus, adenovirus, and rotavirus), seven Escherichia coli virulence genes (ECVG), and human-specific Bacteroidales was assessed in hand rinses and household stored drinking water in Bagamoyo, Tanzania. Using a matched case-control study design, we examined the relationship between contamination of hands and water with these markers and child diarrhea. We found that the presence of ECVG in household stored water was associated with a significant decrease in the odds of a child within the home having diarrhea (OR = 0.51; 95% confidence interval 0.27-0.93). We also evaluated water management and hygiene behaviors. Recent hand contact with water or food was positively associated with detection of enteric pathogen markers on hands, as was relatively lower volumes of water reportedly used for daily hand washing. Enteropathogen markers in stored drinking water were more likely found among households in which the markers were also detected on hands, as well as in households with unimproved water supply and sanitation infrastructure. The prevalence of enteric pathogen genes and the human-specific Bacteroidales fecal marker in stored water and on hands suggests extensive environmental contamination within homes both with and without reported child diarrhea. Better stored water quality among households with diarrhea indicates caregivers with sick children may be more likely to ensure safe drinking water in the home. Interventions to increase the quantity of water available for hand washing, and to improve food hygiene, may reduce exposure to enteric pathogens in the domestic environment

Small-cell lung cancer in England: trends in survival and chemotherapy using the National Lung Cancer Audit

Background: The purpose of this study was to identify trends in survival and chemotherapy use for individuals with smallcell lung cancer (SCLC) in England using the National Lung Cancer Audit (NLCA). Methods: We used data from the NLCA database to identify people with histologically proven SCLC from 2004–2011. We calculated the median survival by stage and assessed whether patient characteristics changed over time. We also assessed whether the proportion of patients with records of chemotherapy and/or radiotherapy changed over time. Results: 18,513 patients were diagnosed with SCLC in our cohort. The median survival was 6 months for all patients, 1 year for those with limited stage and 4 months for extensive stage. 69% received chemotherapy and this proportion changed very slightly over time (test for trends p = 0.055). Age and performance status of patients remained stable over the study period, but the proportion of patients staged increased (p-value,0.001), mainly because of improved data completeness. There has been an increase in the proportion of patients that had a record of receiving both chemotherapy and radiotherapy each year (from 19% to 40% in limited and from 9% to 21% in extensive stage from 2004 to 2011). Patients who received chemotherapy with radiotherapy had better survival compared with any other treatment (HR 0.24, 95% CI 0.23–0.25). Conclusion: Since 2004, when the NLCA was established, the proportion of patients with SCLC having chemotherapy has remained static. We have found an upward trend in the proportion of patients receiving both chemotherapy and radiotherapy which corresponded to a better survival in this group, but as it only applied for a small proportion of patients, it was not enough to change the overall survival