2,475 research outputs found

    What's the problem? : an investigation into the social construction of 'problems' through the case of boys and their education

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    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Testing the effectiveness of integrating community-based approaches for encouraging abandonment of female genital cutting into CARE\u27s reproductive health programs in Ethiopia and Kenya

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    CARE International, with technical support from the Frontiers in Reproductive Health Program completed a study in Ethiopia and Kenya designed to test the effectiveness of education activities using behavior change communication (BCC) approaches and advocacy activities by religious and other key leaders to abandon female genital cutting (FGC). In Ethiopia, the increased knowledge of harmful FGC effects and human rights issues translated to a positive attitude in support of FGC abandonment and an intention not to cut their daughters in the future. In Kenya, the analysis indicated mixed results in attitude and intended behavior change

    From pilot to program: Scaling up the Kenya Adolescent Reproductive Health Project

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    The Population Council’s Frontiers in Reproductive Health Program and the Program for Appropriate Technology in Heath collaborated with three Government of Kenya ministries—Education; Health; and Gender, Sports, Culture and Social Services—to design and implement the Kenya Adolescent Reproductive Health Project with the goals of: improving knowledge about reproductive health and encouraging a responsible and healthy attitude toward sexuality among adolescents, delaying the onset of sexual activity among younger adolescents, and decreasing risky behaviors among sexually active adolescents. Key findings from the pilot project showed that the three ministries could successfully implement these interventions with high participation among parents and youth. For these efforts to be sustainable, partners should be involved and willing to integrate activities within their respective programs, share costs, and create a favorable policy and legislative environment

    MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

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    Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

    Verbal instructions override the meaning of facial expressions

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    Psychological research has long acknowledged that facial expressions can implicitly trigger affective psychophysiological responses. However, whether verbal information can alter the meaning of facial emotions and corresponding response patterns has not been tested. This study examined emotional facial expressions as cues for instructed threat-of-shock or safety, with a focus on defensive responding. In addition, reversal instructions were introduced to test the impact of explicit safety instructions on fear extinction. Forty participants were instructed that they would receive unpleasant electric shocks, for instance, when viewing happy but not angry faces. In a second block, instructions were reversed (e.g., now angry faces cued shock). Happy, neutral, and angry faces were repeatedly presented, and auditory startle probes were delivered in half of the trials. The defensive startle reflex was potentiated for threat compared to safety cues. Importantly, this effect occurred regardless of whether threat was cued by happy or angry expressions. Although the typical pattern of response habituation was observed, defense activation to newly instructed threat cues remained significantly enhanced in the second part of the experiment, and it was more pronounced in more socially anxious participants. Thus, anxious individuals did not exhibit more pronounced defense activation compared to less anxious participants, but their defense activation was more persistent

    Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

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    Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

    Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

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    The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of s=1.96\sqrt s =1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is AFBttˉ=0.128±0.025A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions

    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

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    Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio
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