A model for cyclotron resonance scattering features

(abbreviated version of the abstract) We study the physics of cyclotron line formation in the high-energy spectra of accreting X-ray pulsars using Monte Carlo methods, assuming that the line-forming region is a low-density electron plasma in a sub-critical magnetic field. We investigate the dependence of the shape of the fundamental line on angle, geometry, optical depth and temperature. We also discuss variations of the line ratios for non-uniform magnetic fields. These numerical predictions for the line profiles are linked to results from observational data analysis using an XSPEC model based on the Monte Carlo simulations. We apply this model to observational data from RXTE and INTEGRAL. The predicted strong emission wings of the fundamental cyclotron feature are not found in observational data, hinting at a bottom illuminated slab geometry for line formation.Comment: 16 pages, 15 figures, Astron. Astrophys. (in press

How to screen for non-adherence to antihypertensive therapy

The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians’ perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography–tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease

In Vitro Models for Studying Secondary Plant Metabolite Digestion and Bioaccessibility

There is an increased interest in secondary plant metabolites, such as polyphenols and carotenoids, due to their proposed health benefits. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly, and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed and employed to predict their release from the food matrix, bioaccessibility, and assess changes in their profiles prior to absorption. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine, and, occasionally, the large intestine. A plethora of models have been reported, the choice mostly driven by the type of phytochemical studied, whether the purpose is screening or studying under close physiological conditions, and the availability of the model systems. Unfortunately, the diversity of model conditions has hampered the ability to compare results across different studies. For example, there is substantial variability in the time of digestion, concentrations of salts, enzymes, and bile acids used, pH, the inclusion of various digestion stages; and whether chosen conditions are static (with fixed concentrations of enzymes, bile salts, digesta, and so on) or dynamic (varying concentrations of these constituents). This review presents an overview of models that have been employed to study the digestion of both lipophilic and hydrophilic phytochemicals, comparing digestive conditions in vitro and in vivo and, finally, suggests a set of parameters for static models that resemble physiological conditions

Paracrine cyclooxygenase-2 activity by macrophages drives colorectal adenoma progression in the Apc Min/+ mouse model of intestinal tumorigenesis

Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the ApcMin/+ mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas from cLys-Cox-2 x ApcMin/+ mice was associated with significantly increased tumour size (P = 0.025) and multiplicity (P = 0.025), compared with control ApcMin/+ mice. Transgenic macrophage Cox-2 expression was associated with increased dysplasia, epithelial cell Cox-2 expression and submucosal tumour invasion, as well as increased nuclear β-catenin translocation in dysplastic epithelial cells. In vitro studies confirmed that paracrine macrophage Cox-2 signalling drives catenin-related transcription in intestinal epithelial cells. Paracrine macrophage Cox-2 activity drives growth and progression of ApcMin/+ mouse colonic adenomas, linked to increased epithelial cell β-catenin dysregulation. Stromal cell (macrophage) gene regulation and signalling represent valid targets for chemoprevention of colorectal cancer

Beyond self-report: a review of physiological and neuroscientific methods to investigate consumer behavior

The current paper investigates the value and application of a range of physiological and neuroscientific techniques in applied marketing research and consumer science, highlighting new insights from research in social psychology and neuroscience. We review measures of sweat secretion, heart rate, facial muscle activity, eye movements, and electrical brain activity, using techniques including skin conductance, pupillometry, eyetracking, and magnetic brain imaging. For each measure, after a brief explanation of the underlying technique, we illustrate concepts and mechanisms that the measure allows researchers in marketing and consumer science to investigate, with a focus on consumer attitudes and behavior. By providing reviews on recent research that applied these methods in consumer science and relevant related fields, we also highlight methodological and theoretical strengths and limitations, with an emphasis on ecological validity. We argue that the inclusion of physiological and neuroscientific techniques can advance consumer research by providing insights into the often unconscious mechanisms underlying consumer behavior. Therefore, such technologies can help researchers and marketing practitioners understand the mechanisms of consumer behavior and improve predictions of consumer behavior

A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

Anticipation, manifested through decreasing age of onset or increased severity in successive generations, has been noted in several genetic diseases. Statistical methods for genetic anticipation range from a simple use of the paired t -test for age of onset restricted to affected parent-child pairs to a recently proposed random effects model which includes extended pedigree data and unaffected family members [Larsen et al., 2009 ]. A naive use of the paired t -test is biased for the simple reason that age of onset has to be less than the age at ascertainment (interview) for both affected parent and child, and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare the paired t -test with the parametric conditional maximum likelihood approach of Huang and Vieland [ 1997 ] and the nonparametric approach of Rabinowitz and Yang [ 1999 ] in terms of Type I error and power under various simulation settings and departures from the modeling assumptions. We especially investigate the issue of multiplex ascertainment and its effect on the different methods. We then focus on exploring genetic anticipation in Lynch syndrome and analyze new data on the age of onset in affected parent-child pairs from families seen at the University of Michigan Cancer Genetics clinic with a mutation in one of the three main mismatch repair (MMR) genes. In contrast to the clinic-based population, we re-analyze data on a population-based Lynch syndrome cohort, derived from the Danish HNPCC-register. Both datasets indicate evidence of genetic anticipation in Lynch syndrome. We then expand our review to incorporate recently proposed statistical methods that consider family instead of affected pairs as the sampling unit. These prospective censored regression models offer additional flexibility to incorporate unaffected family members, familial correlation and other covariates into the analysis. An expanded dataset from the Danish HNPCC-register is analyzed by this alternative set of methods. Genet. Epidemiol . 34:756-768, 2010.© 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78225/1/20534_ftp.pd

Genetic Variants of the Renin Angiotensin System: Effects on Atherosclerosis in Experimental Models and Humans

The renin angiotensin system (RAS) has profound effects on atherosclerosis development in animal models, which is partially complimented by evidence in the human disease. Although angiotensin II was considered to be the principal effector of the RAS, a broader array of bioactive angiotensin peptides have been identified that have increased the scope of enzymes and receptors in the RAS. Genetic interruption of the synthesis of these peptides has not been extensively performed in experimental or human studies. A few studies demonstrate that interruption of a component of the angiotensin peptide synthesis pathway reduces experimental lesion formation. The evidence in human studies has not been consistent. Conversely, genetic manipulation of the RAS receptors has demonstrated that AT1a receptors are profoundly involved in experimental atherosclerosis. Few studies have reported links of genetic variants of angiotensin II receptors to human atherosclerotic diseases. Further genetic studies are needed to define the role of RAS in atherosclerosis

Non-adherence to antihypertensive medications is related to pill burden in apparent treatment resistant hypertensive individuals

Objective: Non-adherence to medication is present in ≥50% of patients with apparent treatment resistant hypertension. We examined the factors associated with non-adherence as detected by an LC-MS/MS based urine antihypertensive drug assay. Methods: All urine antihypertensive test results, carried out for uncontrolled hypertension (BP persistently >140/90 mmHg) between January 2015 and December 2016 at a single toxicology laboratory were analysed. Drugs detected were compared to the antihypertensive drugs prescribed. Patients were classified as adherent (all drugs detected), partially non-adherent (≥1 prescribed drugs detected) or completely non-adherent (no drugs detected). Demographic and clinical parameters were compared between the adherent and non-adherent groups. Binary logistic regression analysis was performed to determine association between non-adherence and demographic and clinical factors. Results: Data on 300 patients from 9 hypertension centres across the UK were analysed. The median age was 59 years, 47% female, 71% Caucasian , median clinic BP was 176/95 mmHg and the median number of antihypertensive drugs prescribed was four. One hundred and sixty-six (55%) were non-adherent to prescribed medication with 20% of these being completely non-adherent. Non-adherence to antihypertensive medication was independently associated with younger age, female gender, number of antihypertensive drugs prescribed, total number of all medications prescribed (total pill burden) and prescription of a calcium channel blocker. Conclusion: This LC-MS/MS urine analysis-based study suggests the majority of patients with apparent treatment resistant hypertension are non-adherent to prescribed treatment. Factors that are associated with non-adherence, particularly pill burden, should be taken into account while treating these patients

Long-term Effect of CPAP Treatment on Cardiovascular Events in Patients With Resistant Hypertension and Sleep Apnea. Data From the HIPARCO-2 Study

Background: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE. Methods: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3-6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP. Results: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96-2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07-15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2-11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05-1.02; p=0.053). Conclusions: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events