The Efficacy of Hippocampal Stimulation in Preventing Depressive Symptoms

The hippocampus provides negative feedback for the Hypothalamic-Pituitary- Adrenal (HPA) axis. The HPA axis is responsible for producing a response to stressful stimuli. The hippocampus is sensitive to high levels of glucocorticoids (GCs), because of its large number of GC receptors. In times of severe stress, hippocampal function is inhibited and its control over the HPA axis is diminished, leading to hyperactivity of the adrenal glands as well as hypercortisolism, typical of depression. Long-term stress and depression can eventually lead to chronic impairments in cognitive ability, as well as structural damage in the hippocampus. Exercise and environmental enrichment stimulate significant growth and activity in the hippocampus, and have been used successfully as antidepressant treatments in previous studies. However, these previous studies failed to demonstrate whether such treatments are capable of preventing the cognitive symptoms of depression during times of persistent chronic prolonged stress. Previous research has also evaded the possibility of a potential additive effect when both treatments are used in combination. The current study aims to extend previous research in this area by examining both the possibility of a preventative efficacy of hippocampal stimulation during periods of stress, as well the possibility of an additive effect associated with the use of both treatments. Rodents went through a 10-week period of CMS along with concurrent exposure to environmental enrichment, environmental enrichment and exercise, or neither. Sucrose consumption was used as a measure of anhedonia at the 8-week point. At the completion of the 10 week CMS period, spatial memory was measured using the Morris Water Maze and a Novel Object Placement Task. The overall level of spatial memory impairment was determined based on the group means collected during these tests. Overall, results from the current study provide evidence supporting the preventative efficacy of hippocampal stimulation during periods of stress. Whi

Evidence-based retrieval in evidence-based medicine

pre-printObjective: Clinical decisions based on a meta-analysis that is based on an ineffective retrieval strategy may have serious negative consequences for patients. The study objective was to investigate the extent to which meta-analyses report proof of their retrieval strategies' effectiveness. Methods: The authors examined a random sample (n 5 100) of articles in the 1996 to 2002 full-text subset of Ovid MEDLINE indexed as ‘‘meta-analysis.'' We classified the articles in three ways: the article (A) reported both a retrieval strategy in sufficient detail (such that it could be repeated) and with evidence of the strategy's effectiveness, (B) reported a retrieval strategy in sufficient detail but not with evidence of the strategy's effectiveness, or (C) neither reported a strategy in detail nor evidence of the strategy's effectiveness. Articles classified as (A) were further classified according to the level of evidence reported. Results: Of the eighty-nine articles in our final analysis, six (6.7%) were classified as category (A), fifty-seven (64%) as (B), and twenty-six (29%) as (C). Articles in category (A) reported a previously validated search, a published strategy, or strategy based on expert opinion. Conclusion: Peer-review standards must be developed that require authors of meta-analyses to report evidence for the effectiveness of their retrieval strategies

Imiglucerase in the treatment of Gaucher disease: a history and perspective

The scientific and therapeutic development of imiglucerase (Cerezyme®) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease

Adapting to Misspecification

Empirical research typically involves a robustness-efficiency tradeoff. A researcher seeking to estimate a scalar parameter can invoke strong assumptions to motivate a restricted estimator that is precise but may be heavily biased, or they can relax some of these assumptions to motivate a more robust, but variable, unrestricted estimator. When a bound on the bias of the restricted estimator is available, it is optimal to shrink the unrestricted estimator towards the restricted estimator. For settings where a bound on the bias of the restricted estimator is unknown, we propose adaptive shrinkage estimators that minimize the percentage increase in worst case risk relative to an oracle that knows the bound. We show that adaptive estimators solve a weighted convex minimax problem and provide lookup tables facilitating their rapid computation. Revisiting five empirical studies where questions of model specification arise, we examine the advantages of adapting to -- rather than testing for -- misspecification.Comment: 69 pages, 12 figure

Computing equilibrium states of cholesteric liquid crystals in elliptical channels with deflation algorithms

We study the problem of a cholesteric liquid crystal confined to an elliptical channel. The system is geometrically frustrated because the cholesteric prefers to adopt a uniform rate of twist deformation, but the elliptical domain precludes this. The frustration is resolved by deformation of the layers or introduction of defects, leading to a particularly rich family of equilibrium configurations. To identify the solution set, we adapt and apply a new family of algorithms, known as deflation methods, that iteratively modify the free energy extremisation problem by removing previously known solutions. A second algorithm, deflated continuation, is used to track solution branches as a function of the aspect ratio of the ellipse and preferred pitch of the cholesteric.Comment: 9 pages, 6 figure

Spectral Effects of Strong Chi-2 Non-Linearity for Quantum Processing

Optical $\chi^{(2)}$ non-linearity can be used for parametric amplification and producing down-converted entangled photon pairs that have broad applications. It is known that weak non-linear media exhibit dispersion and produce a frequency response. It is therefore of interest to know how spectral effects of a strong $\chi^{(2)}$ crystal affect the performance. Here we model the spectral effects of the dispersion of a strong $\chi^{(2)}$ crystal and illustrate how this affects its ability to perform Bell measurements and influence the performance of a quantum gates that employ such a Bell measurement. We show that a Dyson series expansion of the unitary operator is necessary in general, leading to unwanted spectral entanglement. We identify a limiting situation employing periodic poling, in which a Taylor series expansion is a good approximation and this entanglement can be removed.Comment: Will be submitted to PR

Observations of X-rays and Thermal Dust Emission from the Supernova Remnant Kes 75

We present Spitzer Space Telescope and Chandra X-ray Observatory observations of the composite Galactic supernova remnant Kes 75 (G29.7-0.3). We use the detected flux at 24 microns and hot gas parameters from fitting spectra from new, deep X-ray observations to constrain models of dust emission, obtaining a dust-to-gas mass ratio M_dust/M_gas ~0.001. We find that a two-component thermal model, nominally representing shocked swept-up interstellar or circumstellar material and reverse-shocked ejecta, adequately fits the X-ray spectrum, albeit with somewhat high implied densities for both components. We surmise that this model implies a Wolf-Rayet progenitor for the remnant. We also present infrared flux upper limits for the central pulsar wind nebula.Comment: 7 pages, 2 tables, 4 figures, uses emulateapj. Accepted for publication in Ap

Oxy Fuel for Clean Energy Generation

This process explores several concentrations of oxygen-enriched air streams (oxy fuel) in combination with natural gas to generate steam for a steam turbine power plant with 30 MW capacity. The proposed location for this plant is the gulf coast of the United States. The oxy fuel concentrations tested were 36 mol. %, 53 mol. %, and 95 mol. %. Nitrogen removed from air would be sold as well as the 30 MW of electricity. The three oxygen purities were not profitable for the most realistic prices of electricity, nitrogen, and natural gas. However, the scenarios were all profitable with prices of nitrogen above $0.015/lb. Additionally, the profitability could be improved with higher electricity prices or better thermal efficiency. A key takeaway is that the level of oxygen purity did not have a major effect on profitability for a given nitrogen price

Does a Crossover Age Effect Exist for African American and Hispanic Binge Drinkers? Findings from the 2010 to 2013 National Study on Drug Use and Health

BACKGROUND: Among general population studies, lower rates of binge drinking tend to be found among African Americans and Hispanics compared to Whites. However, among older adult populations, minority groups have been shown to be at higher risk for binge drinking, suggesting the presence of a crossover effect from low to high risk as a function of age. To date, limited research has examined the crossover effect among African American and Hispanic populations compared to non-Hispanic Whites across large developmental time frames or explored variation in risk based on income or gender. This study aimed to fill these gaps in the literature. METHODS: Data were compiled from the 2010 to 2013 National Survey on Drug Use and Health surveys, which provide annual, nationally representative data on substance use behaviors among individuals aged 12 and older. Hispanic, non-Hispanic African American, and non-Hispanic White respondents were included (N = 205,198) in the analyses. RESULTS: A crossover effect was found for African American males and females among the lowest income level (i.e., incomes less than $20,000). Specifically, after controlling for education and marital status, compared to Whites, risk for binge drinking was lower for African American males at ages 18 to 24 and for females at ages 18 to 34, but higher for both African American males and females at ages 50 to 64. No crossover effect was found for Hispanic respondents. CONCLUSIONS: Although African Americans are generally at lower risk for binge drinking, risk appears to increase disproportionately with age among those who are impoverished. Explanatory factors, such as social determinants of health prevalent within low-income African American communities (e.g., lower education, violence exposure, housing insecurity) and potential areas for intervention programming are discussed