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Currently, influenza vaccine manufacturers need to produce 1–5 x 107 PFU of each vaccine strain to fill one dose of the current live-attenuated-influenza-vaccine (LAIV). To make a single dose of inactivated vaccine (15 ug of each hemagglutinin), the equivalent of 1010 PFU of each vaccine strains need to be grown. This high dose requirement is a major drawback for manufacturing as well as rapidly sourcing sufficient doses during a pandemic. Using our computer-aided vaccine platform Synthetic Attenuated Virus Engineering (SAVE), we created a vaccine candidate against pandemic H1N1 A/CA/07/2009 (CodaVax-H1N1) with robust efficacy in mice and ferrets, and is protective at a much lower dose than the current LAIV. CodaVax-H1N1 is currently in Phase I/II clinical trials. The hemagglutinin (HA) and neuraminidase (NA) gene segments of A/California/07/2009 (H1N1) (CA07) were "de-optimized" and a LAIV was generated ex silico using DNA synthesis. In DBA/2 mice, vaccination at a very low dose (100 or approximately 1 PFU) with CodaVax-H1N1 prevented disease after lethal challenge with wild-type H1N1. In BALB/c mice, as little as 103 PFU was protective against lethal challenge with mouse-adapted H1N1. In ferrets, CodaVax-H1N1 was more potent compared to currently licensed LAIV and still effective at a low dose of 103 PFU at preventing replication of challenge virus. [ABSTRACT FROM AUTHOR]

SummaryPlant responses to elevated atmospheric CO2 have been characterized generally by stomatal closure and enhanced growth rates. These responses are being increasingly incorporated into global climate models that quantify interactions between the biosphere and atmosphere, altering climate predictions from simpler physically based models. However, current information on CO2 responses has been gathered primarily from studies of crop and temperate forest species. In order to apply responses of vegetation to global predictions, CO2 responses in other commonly occurring biomes must be studied. A Free Air CO2 Enrichment (FACE) study is currently underway to examine plant responses to high CO2 in a natural, undisturbed Mojave Desert ecosystem in Nevada, USA. Here we present findings from this study, and its companion glasshouse experiment, demonstrating that field-grown Ephedra nevadensis and glasshouse-grown Larrea tridentata responded to high CO2 with reductions in the ratio of transpirational surface area to sapwood area (LSR) of 33% and 60%, respectively. Thus, leaf-specific hydraulic conductivity increased and stomatal conductance remained constant or was increased under elevated CO2. Field-grown Larrea did not show a reduced LSR under high CO2, and stomatal conductance was reduced in the high CO2 treatment, although the effect was apparent only under conditions of unusually high soil moisture. Both findings suggest that the common paradigm of 20–50% reductions in stomatal conductance under high CO2 may not be applicable to arid ecosystems under most conditions. [ABSTRACT FROM AUTHOR]

SummaryPlant responses to elevated atmospheric CO2 have been characterized generally by stomatal closure and enhanced growth rates. These responses are being increasingly incorporated into global climate models that quantify interactions between the biosphere and atmosphere, altering climate predictions from simpler physically based models. However, current information on CO2 responses has been gathered primarily from studies of crop and temperate forest species. In order to apply responses of vegetation to global predictions, CO2 responses in other commonly occurring biomes must be studied. A Free Air CO2 Enrichment (FACE) study is currently underway to examine plant responses to high CO2 in a natural, undisturbed Mojave Desert ecosystem in Nevada, USA. Here we present findings from this study, and its companion glasshouse experiment, demonstrating that field-grown Ephedra nevadensis and glasshouse-grown Larrea tridentata responded to high CO2 with reductions in the ratio of transpirational surface area to sapwood area (LSR) of 33% and 60%, respectively. Thus, leaf-specific hydraulic conductivity increased and stomatal conductance remained constant or was increased under elevated CO2. Field-grown Larrea did not show a reduced LSR under high CO2, and stomatal conductance was reduced in the high CO2 treatment, although the effect was apparent only under conditions of unusually high soil moisture. Both findings suggest that the common paradigm of 20–50% reductions in stomatal conductance under high CO2 may not be applicable to arid ecosystems under most conditions. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis., Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided., Results: A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG., Conclusions: As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.

Many employer-sponsored health plans and multi-employer health benefit trusts have seen an increase in medical child support orders (MCSOs), and they can anticipate receiving a greater number in the future. Once regulations are final for the national medical support notice (NMSN) required by the Child Support Performance and Incentive Act of 1998, plans should also begin receiving these. In preparation, plan administrators should ensure that they have proper procedures in place for determining whether MCSOs and NMSNs constitute QMCSOs.