A survey to investigate the association of pain, foot disability and quality of life with corns

Background Corns are a common foot problem affecting a large proportion of the population. This study describes the characteristics of corns experienced by 201 participants taking part in a randomised controlled trial to investigate associations between demographic and corn parameters on pain, foot related disability and quality of life (QoL). Methods Pain from the main (index) corn was measured using a visual analogue scale (VAS); foot related disability was assessed with the Foot Disability Questionnaire (now known as the Manchester Foot Pain and Disability Index) and quality of life was recorded with the EQ-5D questionnaire. The effect of demographic and corn parameters on the pain and quality of life outcomes was assessed with analysis of variance (ANOVA) methods. The effect of the same factors on a linear combination of the foot-related disability outcome measures was assessed using multivariate ANOVA methods. Pain was also tested for its mediating properties on the causal pathway between the independent variables and quality of life. Results The mean pain score was 5.29 points on a 10 cm VAS, with females reporting substantively higher pain levels than males. Age affected foot-related disability, with lower levels on all domains of the MFPDI reported in older participants; each year of advancing age was associated with falls of: 0.009 points on the Concern about Appearance (CA) domain; 0.047 points on the Functional Limitation (FL) domain and 0.048 points on the Pain Intensity (PI) domain. Sex and corn type also affected disability, with higher scores reported by females and participants with plantar corns. Conclusions The effect of pain was shown to mediate the relationship between sex and foot-related disability. The presence of plantar corns has a more detrimental effect on QoL than dorsal/inter-digital corns

Nature vs. nurture in the low-density environment: structure and evolution of early-type dwarf galaxies in poor groups

We present the stellar population properties of 13 dwarf galaxies residing in poor groups (low-density environment, LDE) observed with VIMOS@VLT. Ages, metallicities, and [alpha/Fe] ratios were derived from the Lick indices Hbeta, Mgb, Fe5270 and Fe5335 through comparison with our simple stellar population (SSP) models accounting for variable [alpha/Fe] ratios. For a fiducial subsample of 10 early-type dwarfs we derive median values and scatters around the medians of 5.7 \pm 4.4 Gyr, -0.26 \pm 0.28, and -0.04 \pm 0.33 for age, log Z/Zsun, and [alpha/Fe], respectively. For a selection of bright early-type galaxies (ETGs) from the Annibali et al.2007 sample residing in comparable environment we derive median values of 9.8 \pm 4.1 Gyr, 0.06 \pm 0.16, and 0.18 \pm 0.13 for the same stellar population parameters. It follows that dwarfs are on average younger, less metal rich, and less enhanced in the alpha-elements than giants, in agreement with the extrapolation to the low mass regime of the scaling relations derived for giant ETGs. From the total (dwarf + giant) sample we derive that age \propto sigma^{0.39 \pm 0.22}, Z \propto sigma^{0.80 \pm 0.16}, and alpha/Fe \propto sigma^{0.42 \pm 0.22}. We also find correlations with morphology, in the sense that the metallicity and the [alpha/Fe] ratio increase with the Sersic index n or with the bulge-to-total light fraction B/T. The presence of a strong morphology-[alpha/Fe] relation appears to be in contradiction to the possible evolution along the Hubble sequence from low B/T (low n) to high B/T (high n) galaxies. We also investigate the role played by environment comparing the properties of our LDE dwarfs with those of Coma red passive dwarfs from the literature. We find possible evidence that LDE dwarfs experienced more prolonged star formations than Coma dwarfs, however larger data samples are needed to draw more firm conclusions.Comment: Accepted for publication on A&

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

A National Strategy to Develop Pragmatic Clinical Trials Infrastructure

An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

South Pacific Paleogene Climate

International Ocean Discovery Program (IODP) Expedition 378 was designed to recover the first comprehensive set of Paleogene sedimentary sections from a transect of sites strategically positioned in the South Pacific to reconstruct key changes in oceanic and atmospheric circulation. These sites would have provided an unparalleled opportunity to add crucial new data and geographic coverage to existing reconstructions of Paleogene climate. In addition to the ~15 month postponement of Expedition 378 and subsequent port changes resulting in a reduction of the number of primary sites, testing and evaluation of the R/V JOIDES Resolution derrick in the weeks preceding the expedition determined that it would not support deployment of drill strings in excess of 2 km. Because of this determination, only 1 of the originally approved 7 primary sites was drilled. Expedition 378 recovered the first continuously cored, multiple-hole Paleogene sedimentary section from the southern Campbell Plateau at Site U1553. This high–southern latitude site builds on the legacy of Deep Sea Drilling Project (DSDP) Site 277, a single, partially spot cored hole, providing a unique opportunity to refine and augment existing reconstructions of the past ~66 My of climate history. This also includes the discovery of a new siliciclastic unit that had never been drilled before. As the world’s largest ocean, the Pacific Ocean is intricately linked to major changes in the global climate system. Previous drilling in the low-latitude Pacific Ocean during Ocean Drilling Program (ODP) Legs 138 and 199 and Integrated Ocean Drilling Program Expeditions 320 and 321 provided new insights into climate and carbon system dynamics, productivity changes across the zone of divergence, time-dependent calcium carbonate dissolution, bio- and magnetostratigraphy, the location of the Intertropical Convergence Zone, and evolutionary patterns for times of climatic change and upheaval. Expedition 378 in the South Pacific Ocean uniquely complements this work with a high-latitude perspective, especially because appropriate high-latitude records are unobtainable in the Northern Hemisphere of the Pacific Ocean. Site U1553 and the entire corpus of shore-based investigations will significantly contribute to the challenges of the “Climate and Ocean Change: Reading the Past, Informing the Future” theme of the IODP Science Plan (How does Earth’s climate system respond to elevated levels of atmospheric CO2? How resilient is the ocean to chemical perturbations?). Furthermore, Expedition 378 will provide material from the South Pacific Ocean in an area critical for high-latitude climate reconstructions spanning the Paleocene to late Oligocene

Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells

Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985–1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6–5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8–8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population

Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni