A proposed metric for assessing the measurement quality of individual microarrays

BACKGROUND: High-density microarray technology is increasingly applied to study gene expression levels on a large scale. Microarray experiments rely on several critical steps that may introduce error and uncertainty in analyses. These steps include mRNA sample extraction, amplification and labeling, hybridization, and scanning. In some cases this may be manifested as systematic spatial variation on the surface of microarray in which expression measurements within an individual array may vary as a function of geographic position on the array surface. RESULTS: We hypothesized that an index of the degree of spatiality of gene expression measurements associated with their physical geographic locations on an array could indicate the summary of the physical reliability of the microarray. We introduced a novel way to formulate this index using a statistical analysis tool. Our approach regressed gene expression intensity measurements on a polynomial response surface of the microarray's Cartesian coordinates. We demonstrated this method using a fixed model and presented results from real and simulated datasets. CONCLUSION: We demonstrated the potential of such a quantitative metric for assessing the reliability of individual arrays. Moreover, we showed that this procedure can be incorporated into laboratory practice as a means to set quality control specifications and as a tool to determine whether an array has sufficient quality to be retained in terms of spatial correlation of gene expression measurements

Spin-dynamics of the low-dimensional magnet (CH3)2NH2CuCl3

Dimethylammonium copper (II) chloride (also known as DMACuCl3 or MCCL) is a low dimensional S=1/2 quantum spin system proposed to be an alternating ferro-antiferromagnetic chain with similar magnitude ferromagnetic (FM) and antiferromagnetic (AFM) exchange interactions. Subsequently, it was shown that the existing bulk measurements could be adequately modeled by considering DMACuCl3 as independent AFM and FM dimer spin pairs. We present here new inelastic neutron scattering measurements of the spin-excitations in single crystals of DMACuCl3. These results show significant quasi-one-dimensional coupling, however the magnetic excitations do not propagate along the expected direction. We observe a band of excitations with a gap of 0.95 meV and a bandwidth of 0.82 meV.Comment: 3 pages, 2 figures included in text, submitted to proceedings of International Conference on Neutron Scattering, December 200

Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11

The objective of this study was to explore young children’s views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5–11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge

Toward improving practices for submission of diagnostic tissue blocks for National Cancer Institute clinical trials

OBJECTIVES: The National Cancer Institute (NCI) National Clinical Trials Network performs phase II and III clinical trials, which increasingly rely on the submission of diagnostic formalin-fixed, paraffin-embedded tissue blocks for biomarker assessment. Simultaneously, advances in precision oncology require that clinical centers maintain diagnostic specimens for ancillary, standard-of-care diagnostics. This has caused tissue blocks to become a limited resource for advancing the NCI clinical trial enterprise and the practice of modern molecular pathology. METHODS: The NCI convened a 1-day workshop of multidisciplined experts to discuss barriers and strategic solutions to facilitate diagnostic block submission for clinical trial science, from the perspective of patient advocates, legal experts, pathologists, and clinical oncologists. RESULTS: The expert views and opinions were carefully noted and reported. CONCLUSIONS: Recommendations were proposed to reduce institutional barriers and to assist organizations in developing clear policies regarding diagnostic block submission for clinical trials

Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: The TEMPO randomized clinical trial

Background. Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. Methods. Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. Results. Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. Conclusion. At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD

SINEs, evolution and genome structure in the opossum

Short INterspersed Elements (SINEs) are non-autonomous retrotransposons, usually between 100 and 500 base pairs (bp) in length, which are ubiquitous components of eukaryotic genomes. Their activity, distribution, and evolution can be highly informative on genomic structure and evolutionary processes. To determine recent activity, we amplified more than one hundred SINE1 loci in a panel of 43 M. domestica individuals derived from five diverse geographic locations. The SINE1 family has expanded recently enough that many loci were polymorphic, and the SINE1 insertion-based genetic distances among populations reflected geographic distance. Genome-wide comparisons of SINE1 densities and GC content revealed that high SINE1 density is associated with high GC content in a few long and many short spans. Young SINE1s, whether fixed or polymorphic, showed an unbiased GC content preference for insertion, indicating that the GC preference accumulates over long time periods, possibly in periodic bursts. SINE1 evolution is thus broadly similar to human Alu evolution, although it has an independent origin. High GC content adjacent to SINE1s is strongly correlated with bias towards higher AT to GC substitutions and lower GC to AT substitutions. This is consistent with biased gene conversion, and also indicates that like chickens, but unlike eutherian mammals, GC content heterogeneity (isochore structure) is reinforced by substitution processes in the M. domestica genome. Nevertheless, both high and low GC content regions are apparently headed towards lower GC content equilibria, possibly due to a relative shift to lower recombination rates in the recent Monodelphis ancestral lineage. Like eutherians, metatherian (marsupial) mammals have evolved high CpG substitution rates, but this is apparently a convergence in process rather than a shared ancestral state. © 2007 Elsevier B.V. All rights reserved

The TEMPO Trial at 5 Years: Transoral Fundoplication (TIF 2.0) Is Safe, Durable, and Cost-effective.

BACKGROUND: Questions remain about the therapeutic durability of transoral incisionless fundoplication (TIF). In this study, clinical outcomes were evaluated at 5 years post-TIF 2.0. METHODS: A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or ≤2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. Following the 6-month evaluation, all patients in the PPI group elected for crossover to TIF; therefore, all 63 patients underwent TIF 2.0 with EsophyX RESULTS: Of 63 patients, 60 were available at 1 year, 52 at 3 years, and 44 at 5 years for evaluation. Troublesome regurgitation was eliminated in 88% of patients at 1 year, 90% at 3 years, and 86% at 5 years. Resolution of troublesome atypical symptoms was achieved in 82% of patients at 1 year, 88% at 3 years, and 80% at 5 years. No serious adverse events occurred. There were 3 reoperations by the end of the 5-year follow-up. At the 5-year follow-up, 34% of patients were on daily PPI therapy as compared with 100% of patients at screening. The total GERD Health-related quality-of-life score improved by decreasing from 22.2 to 6.8 at 5 years ( P \u3c .001). CONCLUSION: In this patient population, the TIF 2.0 procedure provided safe and sustained long-term elimination of troublesome GERD symptoms

A generation apart? Youth and political participation in Britain

Conventional wisdom holds that young people in Britain are alienated from politics, with some claiming that this reflects a wider crisis of legitimacy that should be met by initiatives to increase citizenship. This article addresses these areas, presenting both panel survey and focus group data from first-time voters. It concludes that, contrary to the findings from many predominantly quantitative studies of political participation, young people are interested in political matters, and do support the democratic process. However they feel a sense of anti-climax having voted for the first time, and are critical of those who have been elected to positions of political power. If they are a generation apart, this is less to do with apathy, and more to do with their engaged scepticism about ‘formal’ politics in Britain