Setting implementation research priorities to reduce preterm births and stillbirths at the community level.

Asha George and colleagues from the GAPPS group report the implementation research priorities to address prematurity and stillbirths at the community level that resulted from their recent expert consensus exercise

Delay in Retreatment of Helicobacter pylori Infection Increases Risk of Upper Gastrointestinal Bleeding

Background & Aims: Little is known about risk of upper gastrointestinal bleeding (UGIB) in patients failed by Helicobacter pylori eradication therapy. We investigated the effects of different time until retreatment, after failure of initial H. pylori eradication therapy, on subsequent risk of UGIB. / Methods: We performed a territory-wide retrospective cohort study of 70,518 patients with H pylori infection who had received their first course of clarithromycin-based triple therapy from January 2003 through December 2012 in Hong Kong. Patients who required retreatment after failed initial therapy (n = 8330, 11.8%) were categorized based on time between initial and final H pylori eradication (3 months or less, 3–12 months, and more than 12 months). We collected clinical data from 30 days after prescription of the last course of H pylori therapy until hospitalization for non-variceal UGIB, death, or the end of the study (30 Jun 2016; median follow-up time, 7.65 years). The primary outcome was difference in development UGIB (determined from ICD-9 codes) between patients who required retreatment and those who did not (reference group). / Results: Compared with the reference group, patients who required retreatment had an overall higher risk of UGIB, even after last eradication therapy (adjusted hazard ratio (HR), 1.50, 95% CI, 1.34–1.69). There was a progressive increase in risk of UGIB with longer time from initial until final eradication therapy: hazard ratio for time less than 3 months, 1.16; 95% CI, 0.88–1.54, hazard ratio for time 3–12 months, 1.35; 95% CI, 1.07–1.69, and hazard ratio for time more than 12 months, 1.68; 95% CI, 1.46–1.94 (P for trend = .038). / Conclusion: In a retrospective study of patients in Hong Kong, we found that those failed by initial H pylori eradication have an increased risk of UGIB, compared to patients who responded to the initial therapy. Risk increased progressively with longer time until retreatment. Early retreatment within 3 months should be considered to minimize subsequent UGIB risk

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)

Exact ground states for the four-electron problem in a Hubbard ladder

The exact ground state of four electrons in an arbitrary large two leg Hubbard ladder is deduced from nine analytic and explicit linear equations. The used procedure is described, and the properties of the ground state are analyzed. The method is based on the construction in r-space of the different type of orthogonal basis wave vectors which span the subspace of the Hilbert space containing the ground state. In order to do this, we start from the possible microconfigurations of the four particles within the system. These microconfigurations are then rotated, translated and spin-reversed in order to build up the basis vectors of the problem. A closed system of nine analytic linear equations is obtained whose secular equation, by its minimum energy solution, provides the ground state energy and the ground state wave function of the model.Comment: 10 pages, 7 figure

A biophysical model of the early olfactory system of honeybees

Experimental measurements often can only provide limited data from an animal’s sensory system. In addition, they exhibit large trial-to-trial and animal-to-animal variability. These limitations pose challenges to building mathematical models intended to make biologically relevant predictions. Here, we present a mathematical model of the early olfactory system of honeybees aiming to overcome these limitations. The model generates olfactory response patterns which conform to the statistics derived from experimental data for a variety of their properties. This allows considering the full dimensionality of the sensory input space as well as avoiding overfitting the underlying data sets. Several known biological mechanisms, including processes of chemical binding and activation of receptors, and spike generation and transmission in the antennal lobe network, are incorporated in the model at a minimal level. It can therefore be used to study how experimentally observed phenomena are shaped by these underlying biophysical processes. We verified that our model can replicate some key experimental findings that were not used when building it. Given appropriate data, our model can be generalized to the early olfactory systems of other insects. It hence provides a possible framework for future numerical and analytical studies of olfactory processing in insects

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients

OBJECTIVES: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. METHODS: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aβ) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. RESULTS: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aꞵ42/t-tau (β = -1.52, 95%CI = -2.1 to -0.05) and Aꞵ42/p-tau181 (β = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. CONCLUSIONS: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics

Brain-Derived Neurotrophic Factor Ameliorates Brain Stem Cardiovascular Dysregulation during Experimental Temporal Lobe Status Epilepticus

Background: Status epilepticus (SE) is an acute, prolonged epileptic crisis with a mortality rate of 20–30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM), a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF) via an antioxidant action. Methodology/Principal Findings: In a clinically relevant experimental model of temporal lobe SE (TLSE) using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47 phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB), angiotensin AT1 receptor subtype (AT1R), nitric oxide synthase II (NOS II) or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol), a specific antagonist of NADPH oxidase (apocynin) or an AT1R antagonist (losartan) blunted significantly the augmented superoxide anion or phosphorylated p47 phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdn

Heroes and villains of world history across cultures

© 2015 Hanke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedEmergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles.This research was supported by grant RG016-P-10 from the Chiang Ching-Kuo Foundation for International Scholarly Exchange (http://www.cckf.org.tw/). Religion Culture Entropy China Democracy Economic histor