Superimposed vibration confers no additional benefit compared with resistance training alone

Eighteen participants (22-43 years) were randomly allocated to one of two groups: resistance training combined with vibration (VIB; five males, four females) or resistance training alone (CON; five males, four females). Each participant trained three sessions per week (three sets of 10 seated calf raises against a load, which was increased progressively from 75% of one repetition maximum (1RM) to 90% 1RM for 4 weeks. For the VIB group, a vibratory stimulus (30 Hz, 2.5 mm amplitude) was applied to the soles of the feet by a vibration platform. The two groups did not differ significantly with respect to the total amount of work performed during training. Both groups showed a significant increase in maximum voluntary contraction and 1RM (P

Surface localisation of photosensitisers on intraocular lens biomaterials for prevention of infectious endophthalmitis and retinal protection

Cataract surgery is one of the most commonly-practiced surgical procedures in Western medicine, and, while complications are rare, the most serious is infectious postoperative endophthalmitis. Bacteria may adhere to the implanted intraocular lens (IOL) and subsequent biofilm formation can lead to a chronic, difficult to treat infection. To date, no method to reduce the incidence of infectious endophthalmitis through bacterial elimination, while retaining optical transparency, has been reported. In this study we report a method to optimise the localisation of a cationic porphyrin at the surface of suitable acrylate copolymers, which is the first point of contact with potential pathogens. The porphyrin catalytically generates short-lived singlet oxygen, in the presence of visible light, which kills adherent bacteria indiscriminately. By restricting the photosensitiser to the surface of the biomaterial, reduction in optical transparency is minimised without affecting efficacy of singlet oxygen production. Hydrogel IOL biomaterials incorporating either methacrylic acid (MAA) or methyl methacrylate (MMA) co-monomers allow tuning of the hydrophobic and anionic properties to optimise the localisation of porphyrin. Physiochemical and antimicrobial properties of the materials have been characterised, giving candidate materials with self-generating, persistent anti-infective character against Gram-positive and Gram-negative organisms. Importantly, incorporation of porphyrin can also serve to protect the retina by filtering damaging shortwave visible light, due to the Soret absorption (?max) 430 nm). © 2012 Elsevier Ltd. All rights reserved.

2DRMP-G: Migrating a large-scale numerical mathematical application to a grid environment

We report on the migration of a traditional, single architecture application to a grid application using heterogeneous resources. We focus on the use of the UK e-Science Level 2 grid (UKL2G) which provides a heterogeneous collection of resources distributed within the UK. We discuss the solution architecture, the performance of our application, its future development as a grid-based application and comment on the lessons we have learned in using a grid infrastructure for large-scale numerical problems.

Pharmacogenomic Profiling and Pathway Analyses Identify MAPK-Dependent Migration as an Acute Response to SN38 in p53 Null and p53-Mutant Colorectal Cancer Cells.

The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown to have p53-independent anticancer activity. The aim of this study was to identify the p53-independent signaling mechanisms activated by irinotecan. Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Unsupervised analysis methods showed that p53 status had a highly significant impact on gene expression changes in response to SN38. Pathway analysis indicated that pathways involved in cell motility [adherens junction, focal adhesion, mitogen-activated protein kinase (MAPK), and regulation of the actin cytoskeleton] were significantly activated in p53 null cells, but not p53 wild-type cells, following SN38 treatment. In functional assays, SN38 treatment increased the migratory potential of p53 null and p53-mutant colorectal cancer cell lines, but not p53 wild-type lines. Moreover, p53 null SN38-resistant cells were found to migrate at a faster rate than parental drug-sensitive p53 null cells, whereas p53 wild-type SN38-resistant cells failed to migrate. Notably, cotreatment with inhibitors of the MAPK pathway inhibited the increased migration observed following SN38 treatment in p53 null and p53-mutant cells. Thus, in the absence of wild-type p53, SN38 promotes migration of colorectal cancer cells, and inhibiting MAPK blocks this potentially prometastatic adaptive response to this anticancer drug.

Association analysis of proopiomelanocortin (POMC) haplotypes in type 1 diabetes in a UK population

Aim

To assess the association of POMC haplotype-tagged single nucleotide polymorphisms (htSNPs) with the development of type 1 diabetes (T1D) in a Caucasian population.

Methods

All exons, intron 1, and approximately 6-kb upstream and 3-kb downstream of the POMC gene were bidirectionally resequenced to identify DNA polymorphisms in 30 individuals. Allele frequencies were determined (60 chromosomes) and efficient htSNPs were selected using the htSNP2 programme. Genotyping was performed in 390 cases, 339 controls and 245 T1D parent-offspring trios, using Taqman, Sequenom and direct-sequencing technologies.

Results

Thirteen polymorphisms (two novel) with a minor allele frequency greater than 1% were identified. Six POMC htSNPs (rs3754863 G>A, ss161151662 A>G, rs3754860 C>T, rs1009388 G>C, rs3769671 A>C, rs1042571 G>A) were identified. Allele and haplotype frequencies were similar between case and control groups (P>0.60 by permutation test), and assessment of allele transmission distortion from informative parents to affected offspring also failed to find any association. Stratification of these analyses for age-at-onset and HLA-DR risk group (DR3/DR4) revealed no significant associations. A haplotype block of 9.86-kb from rs3754863 to rs1042571 was identified, encompassing the POMC gene. Comparison of haplotype frequencies identified the GGCGAG haplotype as protective against T1D in 12.9% of cases vs. 18.3% of controls: ?2=8.18, Pc=0.03 by permutation test.

Conclusion

The POMC SNP haplotype GGCGAG may have a protective effect against T1D in the UK population. However, this finding needs to be replicated, and the cellular and molecular processes influenced by this POMC haplotype determined to fully appreciate its impact.

Migratory navigation in birds: new opportunities in an era of fast-developing tracking technology

Birds have remained the dominant model for studying the mechanisms of animal navigation for decades, with much of what has been discovered coming from laboratory studies or model systems. The miniaturisation of tracking technology in recent years now promises opportunities for studying navigation during migration itself (migratory navigation) on an unprecedented scale. Even if migration tracking studies are principally being designed for other purposes, we argue that attention to salient environmental variables during the design or analysis of a study may enable a host of navigational questions to be addressed, greatly enriching the field. We explore candidate variables in the form of a series of contrasts (e. g. land vs ocean or night vs day migration), which may vary naturally between migratory species, populations or even within the life span of a migrating individual. We discuss how these contrasts might help address questions of sensory mechanisms, spatiotemporal representational strategies and adaptive variation in navigational ability. We suggest that this comparative approach may help enrich our knowledge about the natural history of migratory navigation in birds.

Psycho-educational group intervention for family caregivers of hospitalized palliative care patients:pilot study

Family caregivers of patients requiring palliative care commonly experience physical, social, and psychological burdens. Although family caregivers are acknowledged as valid service recipients of palliative care, many have unmet needs, and systematic reviews have shown there are limited evidence-based supportive interventions.

Research priorities associated with family caregivers in palliative care:international perspectives

Reviews of the literature have consistently highlighted significant gaps with regard to research associated with family caregivers within the context of palliative care. We sought to determine a priority driven research agenda for this field of inquiry.

Guidelines for the psychosocial and bereavement support of family caregivers of palliative care patients

Support for family caregivers, including bereavement follow-up, is a core function of palliative care. Many caregivers acknowledge positive aspects associated with the role; however a considerable proportion will experience poor psychological, social, financial, spiritual, and physical well-being and some will suffer from complicated grief. Many family caregivers have unmet needs and would like more information, preparation, and support to assist them in the caregiving role. There is a shortage of evidence-based strategies to guide health professionals in providing optimal support while the caregiver is providing care and after the patient's death.

Ordering effects and choice set awareness in repeat-response stated preference studies

We present an experiment designed to investigate the presence and nature of ordering effects within repeat-response stated preference (SP) studies. Our experiment takes the form of a large sample, full-factorial, discrete choice SP exercise investigating preferences for tap water quality improvements. Our study simultaneously investigates a variety of different forms of position-dependent and precedent-dependent ordering effect in preferences for attributes and options and in response randomness. We also examine whether advanced disclosure of the choice tasks impacts on the probability of exhibiting ordering effects of those different types. We analyze our data both non-parametrically and parametrically and find robust evidence for ordering effects. We also find that the patterns of order effect in respondents' preferences are significantly changed but not eradicated by the advanced disclosure of choice tasks a finding that offers insights into the choice behaviors underpinning order effects. © 2011 Elsevier Inc.