Factors associated with strain in co-resident spouses of patients following stroke

Objective: To identify the factors associated with carer strain following stroke. Design: Co-resident spouses of stroke patients were sent questionnaire measures of their perceptions of strain, stress, mood, handicap, adjustment, social support, life satisfaction and personality, and patient’s mood and independence in activities of daily living. Setting: Stroke spouses were identified from the stroke register at City Hospital, Nottingham. Results: In a sample of 222 carers, 37% had significant strain. Strain was highly correlated with negative affectivity on the Positive and Negative Affectivity Scale, carer mood on the General Health Questionnaire-12 (GHQ-12) and carer’s perceptions of patient’s independence in activities of daily living on the Extended Activities of Daily Living Scale (EADL). Logistic regression analysis of 96 of these carers supported the correlations and showed three factors, carer GHQ-12, patient EADL and negative affectivity, were independently associated with carer strain. Conclusion: The relationship between these factors and strain needs to be tested prospectively. Early identification of carers who may be at risk of strain later on will enable services to be targeted at prevention rather than cure

Local is not always better: the impact of climate information on values, behavior and policy support

In the current research, we experimentally examined the effect of providing local or global information about the impacts of climate change on individuals’ perceived importance of climate change and on their willingness to take action to address it, including policy support. We examined these relationships in the context of individuals’ general value orientations. Our findings, from 99 US residents, suggest that different kinds of climate information (local, global, or none) interact with values vis-à-vis our dependent variables. Specifically, while self-transcendent values predict perceived importance and pro-environmental behavior across all three information conditions, the effect on policy support is less clear. Furthermore, we detected a “reactance effect” where individuals with self-enhancing values who read local information thought that climate change was less important and were less willing to engage in pro-environmental behavior and support policy than self-enhancing individuals in the other information conditions. These results suggest that policy makers and public communicators may want to be cognizant of their audience’s general value orientation. Local information may not only be ineffective but may also prove counterproductive with individuals whose value orientations are more self-enhancing than self-transcendent

Alternative Splicing at a NAGNAG Acceptor Site as a Novel Phenotype Modifier

Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies

Extracellular Superoxide Dismutase Protects Histoplasma Yeast Cells from Host-Derived Oxidative Stress

In order to establish infections within the mammalian host, pathogens must protect themselves against toxic reactive oxygen species produced by phagocytes of the immune system. The fungal pathogen Histoplasma capsulatum infects both neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to survive in these phagocytes have not been fully elucidated. We show that Histoplasma yeasts produce a superoxide dismutase (Sod3) and direct it to the extracellular environment via N-terminal and C-terminal signals which promote its secretion and association with the yeast cell surface. This localization permits Sod3 to protect yeasts specifically from exogenous superoxide whereas amelioration of endogenous reactive oxygen depends on intracellular dismutases such as Sod1. While infection of resting macrophages by Histoplasma does not stimulate the phagocyte oxidative burst, interaction with polymorphonuclear leukocytes (PMNs) and cytokine-activated macrophages triggers production of reactive oxygen species (ROS). Histoplasma yeasts producing Sod3 survive co-incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated through oxidative killing similar to the effect of phagocytes on Candida albicans yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo. Without Sod3, Histoplasma yeasts are attenuated in their ability to establish respiratory infections and are rapidly cleared with the onset of adaptive immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts unable to produce superoxide due to loss of the NADPH-oxidase function. These results demonstrate that phagocyte-produced ROS contributes to the immune response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival

Attaining the canopy in dry and moist tropical forests: strong differences in tree growth trajectories reflect variation in growing conditions

Availability of light and water differs between tropical moist and dry forests, with typically higher understorey light levels and lower water availability in the latter. Therefore, growth trajectories of juvenile trees—those that have not attained the canopy—are likely governed by temporal fluctuations in light availability in moist forests (suppressions and releases), and by spatial heterogeneity in water availability in dry forests. In this study, we compared juvenile growth trajectories of Cedrela odorata in a dry (Mexico) and a moist forest (Bolivia) using tree rings. We tested the following specific hypotheses: (1) moist forest juveniles show more and longer suppressions, and more and stronger releases; (2) moist forest juveniles exhibit wider variation in canopy accession pattern, i.e. the typical growth trajectory to the canopy; (3) growth variation among dry forest juveniles persists over longer time due to spatial heterogeneity in water availability. As expected, the proportion of suppressed juveniles was higher in moist than in dry forest (72 vs. 17%). Moist forest suppressions also lasted longer (9 vs. 5 years). The proportion of juveniles that experienced releases in moist forest (76%) was higher than in dry forest (41%), and releases in moist forests were much stronger. Trees in the moist forest also had a wider variation in canopy accession patterns compared to the dry forest. Our results also showed that growth variation among juvenile trees persisted over substantially longer periods of time in dry forest (>64 years) compared to moist forest (12 years), most probably because of larger persistent spatial variation in water availability. Our results suggest that periodic increases in light availability are more important for attaining the canopy in moist forests, and that spatial heterogeneity in water availability governs long-term tree growth in dry forests

Does urbanization explain differences in interactions between an insect herbivore and its natural enemies and mutualists?

Urbanization can alter the composition of arthropod communities. However, little is known about how urbanization affects ecological interactions. Using experimental colonies of the black bean aphid Aphis fabae Scopoli reared on Vicia faba L, we asked if patterns of predator-prey, host-parasitoid and ant-aphid mutualisms varied along an urbanization gradient across a large town in southern England. We recorded the presence of naturally occurring predators, parasitoid wasps and mutualistic ants together with aphid abundance. We examined how biotic (green areas and plant richness) and abiotic features (impervious surfaces and distance to town center) affected (1) aphid colony size, (2) the likelihood of finding predators, mutualistic ants and aphid mummies (indicating the presence of parasitoids), and (3) how the interplay among these factors affected patterns of parasitoid attack, predator abundance, mutualistic interactions and aphid abundance. The best model to predict aphid abundance was the number of mutualistic ants attending the colonies. Aphid predators responded negatively to both the proportion of impervious surfaces and to the number of mutualistic ants farming the colonies, and positively to aphid population size, whereas parasitized aphids were found in colonies with higher numbers of aphids and ants. The number of mutualistic ants attending was positively associated with aphid colony size and negatively with the number of aphid predators. Our findings suggest that for insect-natural enemy interactions, urbanization may affect some groups, while not influencing others, and that local effects (mutualists, host plant presence) will also be key determinants of how urban ecological communities are formed

Effects and feasibility of a standardised orientation and mobility training in using an identification cane for older adults with low vision: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Orientation and mobility training (O&M-training) in using an identification cane, also called symbol cane, is provided to people with low vision to facilitate independent participation in the community. In The Netherlands this training is mainly practice-based because a standardised and validly evaluated O&M-training in using the identification cane is lacking. Recently a standardised O&M-training in using the identification cane was developed. This training consists of two face-to-face sessions and one telephone session during which, in addition to usual care, the client's needs regarding mobility are prioritised, and cognitive restructuring techniques, action planning and contracting are applied to facilitate the use of the cane. This paper presents the design of a randomised controlled trial aimed to evaluate this standardised O&M-training in using the identification cane in older adults with low vision.</p> <p>Methods/design</p> <p>A parallel group randomised controlled trial was designed to compare the standardised O&M-training with usual care, i.e. the O&M-training commonly provided by the mobility trainer. Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial (N = 190). The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility. Secondary outcomes include quality of life, feelings of anxiety, symptoms of depression, fear of falling, and falls history. Data for the effect evaluation are collected by means of telephone interviews at baseline, and at 5 and 17 weeks after the start of the O&M-training. In addition to an effect evaluation, a process evaluation to study the feasibility of the O&M-training is carried out.</p> <p>Discussion</p> <p>The screening procedure for eligible participants started in November 2007 and will continue until October 2009. Preliminary findings regarding the evaluation are expected in the course of 2010. If the standardised O&M-training is more effective than the current O&M-training or, in case of equal effectiveness, is considered more feasible, the training will be embedded in the Dutch national instruction for mobility trainers.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00946062</p

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe