The OPERA trial : a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

Background: The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design: Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion: Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation

Crisis Sentiment in the U.S. Insurance Sector

We use internet search volume data to measure idiosyncratic and market-wide crisis sentiment to explain insurer stock return volatility. We find that market-level crisis sentiment was a highly significant predictor of stock return volatility of U.S. insurers between 2006 and 2010. Higher levels of crisis sentiment are associated with higher levels of price uncertainty. This effect is strongest for insurers with less exposure to the adverse effects of the financial crisis. Further, crisis sentiment also affects the cross-section of movements in insurer stock prices. Our results imply that investors exited insurer stocks mainly due to irrational crisis sentiment rather than a rational assessment of the insurers' actual exposure to the crisis

Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline

Background: As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. Objective: Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. Methods: We measured tibia and patella lead using K-X-ray fluorescence (1991–1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993–1998 and 1995–2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n = 358). Results: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele compared with men with only wild-type alleles (p interaction = 0.03), such that a 15 μg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (p-trend = 0.008). Results for patella lead were similar. Conclusion: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose

Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent

Counsellee’s experience of cancer genetic counselling with pedigrees that automatically incorporate genealogical and cancer database information

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.While pedigree drawing software is often utilised in genetic services, the use of genealogical databases in genetic counselling is unusual. This is mainly because of the unavailability of such databases in most countries. Electronically generated pedigrees used for cancer genetic counselling in Iceland create pedigrees that automatically incorporate information from a large, comprehensive genealogy database and nation-wide cancer registry. The aim of this descriptive qualitative study was to explore counsellees' experiences of genetic services, including family history taking, using these electronically generated pedigrees. Four online focus groups with 19 participants were formed, using an asynchronous posting method. Participants were encouraged to discuss their responses to questions posted on the website by the researcher. The main themes arising were motivation, information and trust, impact of testing and emotional responses. Most of the participants expressed trust in the method of using electronically generated pedigrees, although some voiced worries about information safety. Many experienced worry and anxiety while waiting for results of genetic testing, but limited survival guilt was noted. Family communication was either unchanged or improved following genetic counselling. The use of electronically generated pedigrees was well received by participants, and they trusted the information obtained via the databases. Age did not seem to influence responses. These results may be indicative of the particular culture in Iceland, where genealogical information is well known and freely shared. Further studies are needed to determine whether use of similar approaches to genealogical information gathering may be acceptable elsewhere

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Pressure-temperature evolution of primordial solar system solids during impact-induced compaction

Prior to becoming chondritic meteorites, primordial solids were a poorly consolidated mix of mm-scale igneous inclusions (chondrules) and high-porosity sub-μm dust (matrix). We used high-resolution numerical simulations to track the effect of impact-induced compaction on these materials. Here we show that impact velocities as low as 1.5 km s−1 were capable of heating the matrix to >1,000 K, with pressure–temperature varying by >10 GPa and >1,000 K over ~100 μm. Chondrules were unaffected, acting as heat-sinks: matrix temperature excursions were brief. As impact-induced compaction was a primary and ubiquitous process, our new understanding of its effects requires that key aspects of the chondrite record be re-evaluated: palaeomagnetism, petrography and variability in shock level across meteorite groups. Our data suggest a lithification mechanism for meteorites, and provide a ‘speed limit’ constraint on major compressive impacts that is inconsistent with recent models of solar system orbital architecture that require an early, rapid phase of main-belt collisional evolution

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Perils of paradigm: Complexity, policy design, and the Endocrine Disruptor Screening Program

The Endocrine Disruptor Screening Program (EDSP), mandated by the United States Congress in the Food Quality Protection Act of 1996, attempts to protect public health from adverse endocrine effects of synthetic chemical compounds by establishing a new testing regime. But the complexities and uncertainties of endocrine disruption and its broader regulatory and social context all but ensure the failure of this policy. This article addresses the issues facing EDSP comprehensively and in detail, in order to move beyond the current regulatory paradigm and foster discourse on a positive role for scientists in support of EDSP's end goal: to protect public health

The RNA Chaperone Hfq Is Important for Growth and Stress Tolerance in Francisella novicida

The RNA-binding protein Hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. Hfq has been shown in several bacteria to interact with small regulatory RNAs and act as a post-transcriptional regulator of mRNA stability and translation. Here we examined the impact of Hfq on growth, stress tolerance, and gene expression in the intracellular pathogen Francisella novicida. We present evidence of Hfq involvement in the ability of F. novicida to tolerate several cellular stresses, including heat-shock and oxidative stresses, and alterations in hfq gene expression under these conditions. Furthermore, expression of numerous genes, including several associated with virulence, is altered in a hfq mutant strain suggesting they are regulated directly or indirectly by Hfq. Strikingly, we observed a delayed entry into stationary phase and increased biofilm formation in the hfq mutant. Together, these data demonstrate a critical role for Hfq in F. novicida growth and survival