DeCAF—Discrimination, Comparison, Alignment Tool for 2D PHarmacophores

Comparison of small molecules is a common component of many cheminformatics workflows, including the design of new compounds and libraries as well as side-effect predictions and drug repurposing. Currently, large-scale comparison methods rely mostly on simple fingerprint representation of molecules, which take into account the structural similarities of compounds. Methods that utilize 3D information depend on multiple conformer generation steps, which are computationally expensive and can greatly influence their results. The aim of this study was to augment molecule representation with spatial and physicochemical properties while simultaneously avoiding conformer generation. To achieve this goal, we describe a molecule as an undirected graph in which the nodes correspond to atoms with pharmacophoric properties and the edges of the graph represent the distances between features. This approach combines the benefits of a conformation-free representation of a molecule with additional spatial information. We implemented our approach as an open-source Python module called DeCAF (Discrimination, Comparison, Alignment tool for 2D PHarmacophores), freely available at http://bitbucket.org/marta-sd/decaf. We show DeCAF’s strengths and weaknesses with usage examples and thorough statistical evaluation. Additionally, we show that our method can be manually tweaked to further improve the results for specific tasks. The full dataset on which DeCAF was evaluated and all scripts used to calculate and analyze the results are also provided

Potential and timescales for oxygen depletion in coastal upwelling systems: A box-model analysis

A simple box model is used to examine oxygen depletion in an idealized ocean-margin upwelling system. Near-bottom oxygen depletion is controlled by a competition between flushing with oxygenated offshore source waters and respiration of particulate organic matter produced near the surface and retained near the bottom. Upwelling-supplied nutrients are consumed in the surface box, and some surface particles sink to the bottom where they respire, consuming oxygen. Steady states characterize the potential for hypoxic near-bottom oxygen depletion; this potential is greatest for faster sinking rates, and largely independent of production timescales except in that faster production allows faster sinking. Timescales for oxygen depletion depend on upwelling and productivity differently, however, as oxygen depletion can only be reached in meaningfully short times when productivity is rapid. Hypoxia thus requires fast production, to capture upwelled nutrients, and fast sinking, to deliver the respiration potential to model bottom waters. Combining timescales allows generalizations about tendencies toward hypoxia. If timescales of sinking are comparable to or smaller than the sum of those for respiration and flushing, the steady state will generally be hypoxic, and results indicate optimal timescales and conditions exist to generate hypoxia. For example, the timescale for approach to hypoxia lengthens with stronger upwelling, since surface particle and nutrient are shunted off-shelf, in turn reducing subsurface respiration and oxygen depletion. This suggests that if upwelling winds intensify with climate change the increased forcing could offer mitigation of coastal hypoxia, even as the oxygen levels in upwelled source waters decline

Examining the Multifactorial Nature of Cognitive Aging with Covariance Analysis of Positron Emission Tomography Data

Research has indicated that there may be age-related and Alzheimer's disease (AD) -related reductions in regional cerebral blood flow (rCBF) in the brain. This study explored differences in age- and AD-related rCBF patterns in the context of cognitive aging using a multivariate approach to the analysis of H215O PET data. First, an rCBF covariance pattern that distinguishes between a group of younger and older adults was identified. Individual subject's expression of the identified age-related pattern was significantly correlated with their performance on tests of memory, even after controlling for the effect of age. This finding suggests that subject expression of the covariance pattern explained additional variation in performance on the memory tasks. The age-related covariance pattern was then compared to an AD-related covariance pattern. There was little evidence that the two covariance patterns were similar, and the age-related pattern did a poor job of differentiating between cognitively-healthy older adults and those with probable AD. The findings from this study are consistent with the multifactorial nature of cognitive aging

Personalized Optical Designs and Manipulating Optics: Applications on the Anterior Segment of the Eye

The image-forming properties of the eye can be described in terms of wave aberration. Understanding the link between aberrations and the anterior segment geometry is therefore of crucial importance for (i) comprehending how the eye works, (ii) modelling the optics of individual eyes, (iii) optimizing optical solutions, or (iv) designing surgical strategies. The eye has many innate adaptations that minimize optical aberrations. In most normal young eyes, the magnitude of aberrations of the cornea is significantly larger than for the whole eye, indicating a significant role of the crystalline lens in compensating corneal aberrations. However, due to geometrical and structural changes, this ocular compensation gets disturbed in different anterior segment conditions, such as keratoconus, presbyopia, or cataract. Keratoconus progressively degrades the corneal shape and, consequently, vision in the adolescence, with a prevalence of 0.05% in the general population. Meanwhile, presbyopia and cataract are conditions related to aging that affect the structure of the crystalline lens, one referring to a loss in accommodative amplitude (presbyopia) and the other to a progressive loss of transparency (cataract). Presbyopia affects 100% of the population older than 45¿years of age, ..

Do Neuropsychological Tests Have the Same Meaning in Spanish Speakers as They Do in English Speakers?

OBJECTIVE: The purpose of this study was to examine whether neuropsychological tests translated into Spanish measure the same cognitive constructs as the original English versions. METHOD: Older adult participants (N = 2,664), who did not exhibit dementia from the Washington Heights Inwood Columbia Aging Project (WHICAP), a community-based cohort from northern Manhattan, were evaluated with a comprehensive neuropsychological battery. The study cohort includes both English (n = 1,800) and Spanish speakers (n = 864) evaluated in their language of preference. Invariance analyses were conducted across language groups on a structural equation model comprising four neuropsychological factors (memory, language, visual-spatial ability, and processing speed). RESULTS: The results of the analyses indicated that the four-factor model exhibited partial measurement invariance, demonstrated by invariant factor structure and factor loadings but nonequivalent observed score intercepts. CONCLUSION: The finding of invariant factor structure and factor loadings provides empirical evidence to support the implicit assumption that scores on neuropsychological tests are measuring equivalent psychological traits across these two language groups. At the structural level, the model exhibited invariant factor variances and covariances

Infectious Complications in Obese Patients Following Trauma

Background Obesity is a public health concern in the United States due to its increasing prevalence, especially in younger age groups. Trauma is the most common cause of death for people under aged 40 y. The purpose of this study is to determine the association between obesity and specific infectious complications after traumatic injury. Materials and methods A retrospective analysis was conducted using data from the 2012 National Trauma Data Bank. The National Trauma Data Bank defined obesity as having a body mass index of 30 or greater. Descriptive statistics were calculated and stratified by obesity status. A hierarchical regression model was used to determine the odds of experiencing an infectious complication in patients with obesity while controlling for age, gender, diabetes, number of comorbidities, injury severity, injury mechanism, head injury, and surgical procedure. Results Patients with a body mass index of 30 or greater compared with nonobese patients had increased odds of having an infectious complication (Odds Ratio, 1.59; 1.49-1.69). In addition to obesity, injury severity score greater than 29, age 40 y or older, diabetes, comorbid conditions, and having a surgical procedure were also predictive of an infectious complication. Conclusions Our results indicate that trauma patients with obesity are nearly 60% more likely to develop an infectious complication in the hospital. Infection prevention and control measures should be implemented soon after hospital arrival for patients with obesity, particularly those with operative trauma

Quantifying Cognitive Reserve in Older Adults by Decomposing Episodic Memory Variance: Replication and Extension

The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion in dependent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve

LiveOcean: a daily forecast model of biogeochemistry in Washington marine waters

LiveOcean is a daily forecast model of ocean conditions for the coastal waters of Washington, Oregon, and Vancouver Island, as well as the Salish Sea. It is forced with realistic tides, winds, rivers, and ocean conditions. The model simulates biogeochemical properties including phytoplankton, nitrate, dissolved oxygen, dissolved inorganic carbon, and alkalinity, up to 3 days in the future. It is used for the prediction of ocean acidification events in coastal estuaries, and for harmful algal bloom events on coastal beaches. I will describe the model construction, comparisons with observations, uses, and future developments

Eculizumab discontinuation in atypical haemolytic uraemic syndrome : TMA recurrence risk and renal outcomes

Eculizumab modifies the course of disease in patients with atypical haemolytic uraemic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited. Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated haematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analysed. The primary endpoint was the proportion of patients suffering from thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: estimated glomerular filtration rate changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function. We analysed 151 patients with clinically diagnosed aHUS who had evidence of haematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; seven (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation. Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essentia