Complete Genome Characterisation of a Novel 26th Bluetongue Virus Serotype from Kuwait

Bluetongue virus is the “type” species of the genus Orbivirus, family Reoviridae. Twenty four distinct bluetongue virus (BTV) serotypes have been recognized for decades, any of which is thought to be capable of causing “bluetongue” (BT), an insect-borne disease of ruminants. However, two further BTV serotypes, BTV-25 (Toggenburg orbivirus, from Switzerland) and BTV-26 (from Kuwait) have recently been identified in goats and sheep, respectively. The BTV genome is composed of ten segments of linear dsRNA, encoding 7 virus-structural proteins (VP1 to VP7) and four distinct non-structural (NS) proteins (NS1 to NS4). We report the entire BTV-26 genome sequence (isolate KUW2010/02) and comparisons to other orbiviruses. Highest identity levels were consistently detected with other BTV strains, identifying KUW2010/02 as BTV. The outer-core protein and major BTV serogroup-specific antigen “VP7” showed 98% aa sequence identity with BTV-25, indicating a common ancestry. However, higher level of variation in the nucleotide sequence of Seg-7 (81.2% identity) suggests strong conservation pressures on the protein of these two strains, and that they diverged a long time ago. Comparisons of Seg-2, encoding major outer-capsid component and cell-attachment protein “VP2” identified KUW2010/02 as 26th BTV, within a 12th Seg-2 nucleotype [nucleotype L]. Comparisons of Seg-6, encoding the smaller outer capsid protein VP5, also showed levels of nt/aa variation consistent with identification of KUW2010/02 as BTV-26 (within a 9th Seg-6 nucleotype - nucleotype I). Sequence data for Seg-2 of KUW2010/02 were used to design four sets of oligonucleotide primers for use in BTV-26, type-specific RT-PCR assays. Analyses of other more conserved genome segments placed KUW2010/02 and BTV-25/SWI2008/01 closer to each other than to other “eastern” or “western” BTV strains, but as representatives of two novel and distinct geographic groups (topotypes). Our analyses indicate that all of the BTV genome segments have evolved under strong purifying selection

Participatory citizenship: critical perspectives on client-centred occupational therapy

Background/aims: This article aims to discuss client-centred practice, the current dominant approach within occupational therapy, in relation to participatory citizenship. Occupational therapists work within structures and policies that set boundaries on their engagement with clients, while working with complex, multidimensional social realities. Methods: The authors present a critical discussion shaped by their research, including a survey, discussions at workshops at international conferences, and critical engagement with the literature on occupational therapy, occupation, and citizenship. Conclusion: A focus on citizenship suggests reframing professional development based on the participation in public life of people as citizens of their society. While occupational therapists often refer to clients in the context of communities, groups, families, and wider society, the term client centred practice typically represents a particular view of the individual and may sometimes be too limited in application for a more systemic and societal approach. Significance: The authors question the individual focus which has, until recently, been typical of client-centred occupational therapy. Placing citizenship at the core of intervention is a transformative process that assumes all people are citizens and conceives of health as a collective issue, influencing the way we educate, do research, and practise. Key words: Collective, dis-citizenship, inequalities, professional development, participation, paradigms, occupational justice</p

Acoustic Intensity Causes Perceived Changes in Arousal Levels in Music: An Experimental Investigation

Listener perceptions of changes in the arousal expressed by classical music have been found to correlate with changes in sound intensity/loudness over time. This study manipulated the intensity profiles of different pieces of music in order to test the causal nature of this relationship. Listeners (N = 38) continuously rated their perceptions of the arousal expressed by each piece. An extract from Dvorak's Slavonic Dance Opus 46 No 1 was used to create a variant in which the direction of change in intensity was inverted, while other features were retained. Even though it was only intensity that was inverted, perceived arousal was also inverted. The original intensity profile was also superimposed on three new pieces of music. The time variation in the perceived arousal of all pieces was similar to their intensity profile. Time series analyses revealed that intensity variation was a major influence on the arousal perception in all pieces, in spite of their stylistic diversity

Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise.</p> <p>Methods</p> <p>21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized.</p> <p>Results</p> <p>Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.</p> <p>Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant.</p> <p>Conclusion</p> <p>First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.</p> <p>Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.</p

Childhood leukaemia: long-term excess mortality and the proportion ‘cured'

Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion ‘cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971–2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11–14) to 19 years (95% CI: 14–26) for lymphoid leukaemia (average annual increase of 0.3 years; P<0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates

Daily Physical Activities and Sports in Adult Survivors of Childhood Cancer and Healthy Controls: A Population-Based Questionnaire Survey

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population

EZH2 Depletion Blocks the Proliferation of Colon Cancer Cells

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer

Visual Scan Paths and Recognition of Facial Identity in Autism Spectrum Disorder and Typical Development

Background: Previous research suggests that many individuals with autism spectrum disorder (ASD) have impaired facial identity recognition, and also exhibit abnormal visual scanning of faces. Here, two hypotheses accounting for an association between these observations were tested: i) better facial identity recognition is associated with increased gaze time on the Eye region; ii) better facial identity recognition is associated with increased eye-movements around the face. Methodology and Principal Findings: Eye-movements of 11 children with ASD and 11 age-matched typically developing (TD) controls were recorded whilst they viewed a series of faces, and then completed a two alternative forced-choice recognition memory test for the faces. Scores on the memory task were standardized according to age. In both groups, there was no evidence of an association between the proportion of time spent looking at the Eye region of faces and age-standardized recognition performance, thus the first hypothesis was rejected. However, the 'Dynamic Scanning Index' - which was incremented each time the participant saccaded into and out of one of the core-feature interest areas - was strongly asso ciated with age-standardized face recognition scores in both groups, even after controlling for various other potential predictors of performance. Conclusions and Significance: In support of the second hypothesis, results suggested that increased saccading between core-features was associated with more accurate face recognition ability, both in typical development and ASD. Causal directions of this relationship remain undetermined.10 page(s

Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours