Efficacy of Marketing Strategy for REACH Vitamins

According to the 2009 Global Report, Vitamin A supplementation in children reduces the death rate by 23% in populations at risk of deficiency. REACH Vitamins is a for-profit business that provides a one-year supply of vitamin A to children in underprivileged countries for each bottle of vitamins A, B, C, D, or the multivitamin purchased. The primary objective of this exploratory, qualitative study is to determine if there is a more appropriate marketing strategy for REACH Vitamins compared to the current marketing strategy used. The secondary objective is to determine if REACH Vitamins’ charity motivates consumers to purchase their products. Sample size will not be determined before testing is underway. Participants must be 18 years or older and be able to read and understand English. Physicians, pharmacists, and consumers from southern Ohio will be interviewed in focus groups for their opinions on the best vitamin marketing strategies. Questions will be open-ended and intended to invoke discussion in the group. Notes from the focus group will be written and recorded using Livescribe software. Data will be entered into the program NVivo. Data collection begins in the Fall of 2014

The Lifetime and Powers of FR IIs in Galaxy Clusters

We have identified and studied a sample of 151 FR IIs found in brightest cluster galaxies (BCGs) in the MaxBCG cluster catalog with data from FIRST and NVSS. We have compared the radio luminosities and projected lengths of these FR IIs to the projected length distribution of a range of mock catalogs generated by an FR II model and estimate the FR II lifetime to be 1.9 x 10^8 yr. The uncertainty in the lifetime calculation is a factor of two, due primarily to uncertainties in the ICM density and the FR II axial ratio. We furthermore measure the jet power distribution of FR IIs in BCGs and find that it is well described by a log-normal distribution with a median power of 1.1 x 10^37 W and a coefficient of variation of 2.2. These jet powers are nearly linearly related to the observed luminosities, and this relation is steeper than many other estimates, although it is dependent on the jet model. We investigate correlations between FR II and cluster properties and find that galaxy luminosity is correlated with jet power. This implies that jet power is also correlated with black hole mass, as the stellar luminosity of a BCG should be a good proxy for its spheroid mass and therefore the black hole mass. Jet power, however, is not correlated with cluster richness, nor is FR II lifetime strongly correlated with any cluster properties. We calculate the enthalpy of the lobes to examine the impact of the FR IIs on the ICM and find that heating due to adiabatic expansion is too small to offset radiative cooling by a factor of at least six. In contrast, the jet power is approximately an order of magnitude larger than required to counteract cooling. We conclude that if feedback from FR IIs offsets cooling of the ICM, then heating must be primarily due to another mechanism associated with FR II expansion.Comment: 22 pages, 20 figures. Accepted to ApJ. Added minor clarifications throughout the paper and restructured section 6.2 in response to the referee. A brief video explaining the paper can be found at http://youtu.be/DOq85qUSU-

Near-infrared spectroscopy of powerful compact steep-spectrum radio sources

We have obtained near-infrared spectroscopy of a small sample of powerful Compact Steep-Spectrum (CSS) radio sources mainly, but not exclusively, from the 3CR sample. We find no differences between the distributions in the equivalent width and luminosity of the [OIII] 5007A line for our sample and other larger, presumably older, high-redshift 3C objects, suggesting that the underlying quasar luminosity remains roughly constant as quasars age. We also find a possible broad line in 3C241, adding to recent evidence for broad lines in some radio galaxies.Comment: Accepted by MNRA

MCAM and LAMA4 are highly enriched in tumor blood vessels of renal cell carcinoma and predict patient outcome

The structure and molecular signature of tumor-associated vasculature are distinct from those of the host tissue, offering an opportunity to selectively target the tumor blood vessels. To identify tumor-specific endothelial markers, we performed a microarray on tumor-associated and nonmalignant endothelium collected from patients with renal cell carcinoma (RCC), colorectal carcinoma (CRC), or colorectal liver metastasis (CRM). We identified a panel of genes consistently upregulated by tumor blood vessels of which melanoma cell adhesion molecule (MCAM) and its extracellular matrix interaction partner laminin alpha 4 (LAMA4) emerged as the most consistently expressed genes. This result was subsequently confirmed by immunohistochemical analysis of MCAM and LAMA4 expression in RCC and CRC blood vessels. Strong MCAM and LAMA4 expression was also shown to predict poor survival in RCC, but not in CRC. Notably, MCAM and LAMA4 were enhanced in locally advanced tumors as well as both the primary tumor and secondary metastases. Expression analysis in 18 different cancers and matched healthy tissues revealed vascular MCAM as highly specific in RCC, where it was induced strongly by VEGF, which is highly abundant in this disease. Lastly, MCAM monoclonal antibodies specifically localized to vessels in a murine model of RCC, offering an opportunity for endothelial-specific targeting of anticancer agents. Overall, our findings highlight MCAM and LAMA4 as prime candidates for RCC prognosis and therapeutic targeting

The urgent need to develop novel strategies for the diagnosis and treatment of snakebites

Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills over one hundred thousand people per year. However, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA2 inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, and new treatments are emerging

Impact of Naja nigricollis Venom on the Production of Methaemoglobin

Snakebite envenomation is an affliction currently estimated to be killing upwards of 100,000 people annually. Snakebite is associated with a diverse pathophysiology due to the magnitude of variation in venom composition that is observed worldwide. The haemolytic (i.e., lysis of red blood cells) actions of snake venoms are well documented, although the direct impact of venoms on haemoglobin is not fully understood. Here we report on the varied ability of a multitude of snake venoms to oxidise haemoglobin into methaemoglobin. Moreover, our results demonstrate that the venom of an elapid, the black necked spitting cobra, Naja nigricollis, oxidises oxyhaemoglobin (Fe2+) into methaemoglobin (Fe3+) in a time- and concentration-dependent manner that is unparalleled within the 47 viper and elapid venoms evaluated. The treatment of venom with a reducing agent, dithiothreitol (DTT) is observed to potentiate this effect at higher concentrations, and the use of denatured venom demonstrates that this effect is dependent upon the heat-sensitive proteinaceous elements of the venom. Together, our results suggest that Naja nigricollis venom appears to promote methaemoglobin production to a degree that is rare within the Elapidae family, and this activity appears to be independent of proteolytic activities of venom components on haemoglobin

Forecasting the combined effects of urbanization and climate change on stream ecosystems: from impacts to management options

Streams collect runoff, heat, and sediment from their watersheds, making them highly vulnerable to anthropogenic disturbances such as urbanization and climate change. Forecasting the effects of these disturbances using process-based models is critical to identifying the form and magnitude of likely impacts. Here, we integrate a new biotic model with four previously developed physical models (downscaled climate projections, stream hydrology, geomorphology, and water temperature) to predict how stream fish growth and reproduction will most probably respond to shifts in climate and urbanization over the next several decades.The biotic submodel couples dynamics in fish populations and habitat suitability to predict fish assemblage composition, based on readily available biotic information (preferences for habitat, temperature, and food, and characteristics of spawning) and day-to-day variability in stream conditions.We illustrate the model using Piedmont headwater streams in the Chesapeake Bay watershed of the USA, projecting ten scenarios: Baseline (low urbanization; no on-going construction; and present-day climate); one Urbanization scenario (higher impervious surface, lower forest cover, significant construction activity); four future climate change scenarios [Hadley CM3 and Parallel Climate Models under medium-high (A2) and medium-low (B2) emissions scenarios]; and the same four climate change scenarios plus Urbanization.Urbanization alone depressed growth or reproduction of 8 of 39 species, while climate change alone depressed 22 to 29 species. Almost every recreationally important species (i.e. trouts, basses, sunfishes) and six of the ten currently most common species were predicted to be significantly stressed. The combined effect of climate change and urbanization on adult growth was sometimes large compared to the effect of either stressor alone. Thus, the model predicts considerable change in fish assemblage composition, including loss of diversity.Synthesis and applications. The interaction of climate change and urban growth may entail significant reconfiguring of headwater streams, including a loss of ecosystem structure and services, which will be more costly than climate change alone. On local scales, stakeholders cannot control climate drivers but they can mitigate stream impacts via careful land use. Therefore, to conserve stream ecosystems, we recommend that proactive measures be taken to insure against species loss or severe population declines. Delays will inevitably exacerbate the impacts of both climate change and urbanization on headwater systems

Dysfunction of the mTOR pathway is a risk factor for Alzheimer’s disease

BACKGROUND: The development of disease-modifying therapies for Alzheimer’s disease is hampered by our lack of understanding of the early pathogenic mechanisms and the lack of early biomarkers and risk factors. We have documented the expression pattern of mTOR regulated genes in the frontal cortex of Alzheimer’s disease patients. We have also examined the functional integrity of mTOR signaling in peripheral lymphocytes in Alzheimer’s disease patients relative to healthy controls. RESULTS: In the brain mTOR is seen to control molecular functions related to cell cycle regulation, cell death and several metabolic pathways. These downstream elements of the mTOR signaling cascade are deregulated in the brain of Alzheimer’s disease patients well before the development of pathology. This dysregulation of the mTOR downstream signaling cascade is not restricted to the brain but appears to be systemic and can be detected in peripheral lymphocytes as a reduced Rapamycin response. CONCLUSIONS: The dysfunction of the signaling pathways downstream of mTOR may represent a risk factor for Alzheimer’s disease and is independent of the ApoE status of the patients. We have also identified the molecular substrates of the beneficial effects of Rapamycin on the nervous system. We believe that these results can further inform the development of clinical predictive tests for the risk of Alzheimer’s disease in patients with mild cognitive impairment