Design and construction of an optimal Mueller matrix imaging polarimeter for bio applications

We present a new method for optimizing rotating compensator polarimeters based on the implementation of an elliptical retarder made by placing two linear retarders at an angle offset. By adjusting the angle between the two retarders, the linear retardance can be adjusted to the optimal value of 132deg, achieving a condition number of sqrt(3) over a broad spectroscopic range. This elliptical retarder design is first experimentally demonstrated on a Mueller matrix imaging polarimeter in a back-scattering configuration capable of measuring in-vivo tissue samples over a broad 300 nm wavelength range. The setup is shown to be capable of measuring the orientation of collagen fibers on the surface of skin, and has a standard deviation of < 0.01 for all Mueller matrix elements after repeated measurements. A second polarimeter design also utilizing the elliptical retarder is presented that uses a polarization sensitive camera that detects the first three Stokes components simultaneously and is able to measure the top three rows of a Mueller matrix in only N = 4 measurements, offering significant temporal resolution improvements

Substitutional quantification and set theory

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43184/1/10992_2004_Article_BF00258434.pd

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Peer support for CKD patients and carers : overcoming barriers and facilitating access

Peer support is valued by its users. Nevertheless, there is initial low take-up of formal peer support programmes among patients with chronic kidney disease (CKD), with fewer patients participating than expressing an interest. There is little evidence on reasons for low participation levels. Few studies have examined the perspectives of carers. Objective: To explore with CKD patients and carers their needs, wants and expectations from formal peer support and examine how barriers to participation may be overcome. Methods: Qualitative interviews with a sample of 26 CKD stage five patients and carers. Principles of Grounded Theory were applied to data coding and analysis. Setting: Six NHS Hospital Trusts. Results: Whilst informal peer support might occur naturally and is welcomed, a range of emotional and practical barriers inhibit take‐up of more formalized support. Receptivity varies across time and the disease trajectory and is associated with emotional readiness; patients and carers needing to overcome complex psychological hurdles such as acknowledging support needs. Practical barriers include limited understanding of peer support. An attractive peer relationship is felt to involve reciprocity based on sharing experiences and both giving and receiving support. Establishing rapport is linked with development of reciprocity. Conclusions: There is potential to facilitate active uptake of formal peer support by addressing the identified barriers. Our study suggests several facilitation methods, brought together in a conceptual model, including clinician promotion of peer support as an intervention suitable for anyone with CKD and their carers, and opportunity for choice of peer supporter

High Viral Fitness during Acute HIV-1 Infection

Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection

An economic model of long-term use of celecoxib in patients with osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.</p> <p>Methods</p> <p>We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.</p> <p>Results</p> <p>Our main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was$19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.</p> <p>Conclusion</p> <p>Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.</p

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Neural bases of enhanced attentional control: Lessons from action video game players.

OBJECTIVES: The ability to resist distraction and focus on-task-relevant information while being responsive to changes in the environment is fundamental to goal-directed behavior. Such attentional control abilities are regulated by a constant interplay between previously characterized bottom-up and top-down attentional networks. Here we ask about the neural changes within these two attentional networks that may mediate enhanced attentional control. MATERIALS AND METHODS: To address this question, we contrasted action video game players (AVGPs) and nonvideo game players (NVGPs) in a Posner-cueing paradigm, building on studies documenting enhanced attentional control in AVGPs. RESULTS: Behavioral results indicated a trend for more efficient target processing in AVGPs, and better suppression in rare catch trials for which responses had to be withheld. During the cue period, AVGPs recruited the top-down network less than NVGPs, despite showing comparable validity effects, in line with a greater efficiency of that network in AVGPs. During target processing, as previously shown, recruitment of top-down areas correlated with greater processing difficulties, but only in NVGPs. AVGPs showed no such effect, but rather greater activation across the two networks. In particular, the right temporoparietal junction, middle frontal gyrus, and superior parietal cortex predicted better task performance in catch trials. A functional connectivity analysis revealed enhanced correlated activity in AVGPs compared to NVGPs between parietal and visual areas. CONCLUSIONS: These results point to dynamic functional reconfigurations of top-down and bottom-up attentional networks in AVGPs as attentional demands vary. Aspects of this functional reconfiguration that may act as key signatures of high attentional control are discussed

Design and Construction of an Optimal Mueller Matrix Imaging Polarimeter for Biomedical Applications

A new method for optimizing rotating compensator polarimeters based on the implementation of an elliptical retarder made by placing two linear retarders at an angle offset is formulated. By adjusting the angle between the two retarders, the linear retardance can be adjusted to the optimal value of 132deg, achieving a condition number of sqrt(3) over a broad spectroscopic range. This elliptical retarder design is first experimentally demonstrated on a Mueller matrix imaging polarimeter in a back-scattering configuration capable of measuring in-vivo tissue samples over a broad 300 nm wavelength range. The setup is shown to be capable of measuring the orientation of collagen fibers on the surface of skin, and has a standard deviation of < 0.01 for all Mueller matrix elements after repeated measurements. A second polarimeter design also utilizing the elliptical retarder is presented that uses a polarization sensitive camera that detects the first three Stokes components simultaneously and is able to measure the top three rows of a Mueller matrix in only N = 4 measurements, offering significant temporal resolution improvements