173 research outputs found

    Endophenotypes of executive functions in obsessive compulsive disorder? A meta-analysis in unaffected relatives.

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    Endophenotypes are mediator traits between genetic influences and clinical phenotypes. Meta-analyses have consistently shown modest impairments of executive functioning in obsessive compulsive disorder (OCD) patients compared to healthy controls. Similar deficits have also been reported in unaffected relatives of OCD patients, but have not been quantified. We conducted the first meta-analysis combining all studies investigating executive functioning in unaffected relatives of individuals with OCD to quantify any deficits. A search of Pubmed, Medline and PsychInfo databases identified 21 suitable papers comprising 707 unaffected relatives of OCD patients and 842 healthy controls. Effect sizes were calculated using random effects models. Unaffected relatives displayed a significant impairment in global executive functioning. Analyses of specific executive functioning subdomains revealed impairments in: planning, visuospatial working memory and verbal fluency. Deficits in executive functioning are promising endophenotypes for OCD. To identify further biomarkers of disease risk/resilience in OCD, we suggest examining specific executive functioning domains

    Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

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    Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ2 statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set

    A prevalence survey of every-day activities in pregnancy

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    <p>Abstract</p> <p>Background</p> <p>Research into the effects of common activities during pregnancy is sparse and often contradictory. To examine whether common activities are an acute trigger of pregnancy complications the prevalence of these activities are necessary to determine sample size estimates. The aim of this study is to ascertain the prevalence of selected activities in any seven day period during pregnancy.</p> <p>Methods</p> <p>The study was conducted in the antenatal clinic of a teaching hospital with tertiary obstetric and neonatal care in Sydney, Australia between August 2008 and April 2009. Women who were at least 20 weeks pregnant and able to read English completed a questionnaire to assess whether they had performed a list of activities in the seven days prior to survey completion. Results were analysed using frequency tabulations, contingency table analyses and chi square tests.</p> <p>Results</p> <p>A total of 766 surveys were completed, 29 surveys were excluded as the women completing them were less than 20 weeks pregnant, while 161 women completed the survey more than once. Ninety seven per cent of women completed the survey when approached for the first time, while 87% completed the survey when approached a subsequent time. In the week prior to completing the survey 82.6% of women had consumed a caffeinated beverage, 42.1% had had sexual intercourse, 32.7% had lifted something over 12 kilograms, 21.4% had consumed alcohol and 6.4% had performed vigorous exercise. The weekly prevalence of heavy lifting was higher for multiparous women compared to nulliparous women.</p> <p>Conclusions</p> <p>The results of this study can be used to inform future research into activities as acute triggers of pregnancy complications.</p

    An Ecological Alternative to Snodgrass & Vanderwart: 360 High Quality Colour Images with Norms for Seven Psycholinguistic Variables

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    This work presents a new set of 360 high quality colour images belonging to 23 semantic subcategories. Two hundred and thirty-six Spanish speakers named the items and also provided data from seven relevant psycholinguistic variables: age of acquisition, familiarity, manipulability, name agreement, typicality and visual complexity. Furthermore, we also present lexical frequency data derived from Internet search hits. Apart from the high number of variables evaluated, knowing that it affects the processing of stimuli, this new set presents important advantages over other similar image corpi: (a) this corpus presents a broad number of subcategories and images; for example, this will permit researchers to select stimuli of appropriate difficulty as required, (e.g., to deal with problems derived from ceiling effects); (b) the fact of using coloured stimuli provides a more realistic, ecologically-valid, representation of real life objects. In sum, this set of stimuli provides a useful tool for research on visual object-and word- processing, both in neurological patients and in healthy controls

    Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery

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    Survival of glioblastoma patients has been linked to the completeness of surgical resection. Available data, however, were generated with adjuvant radiotherapy. Data confirming that extensive cytoreduction remains beneficial to patients treated with the current standard, concomitant temozolomide radiochemotherapy, are limited. We therefore analyzed the efficacy of radiochemotherapy for patients with little or no residual tumor after surgery. In this prospective, non-interventional multicenter cohort study, entry criteria were histological diagnosis of glioblastoma, small enhancing or no residual tumor on post-operative MRI, and intended temozolomide radiochemotherapy. The primary study objective was progression-free survival; secondary study objectives were survival and toxicity. Furthermore, the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was investigated in a subgroup of patients. One-hundred and eighty patients were enrolled. Fourteen were excluded by patient request or failure to initiate radiochemotherapy. Twenty-three patients had non-evaluable post-operative imaging. Thus, 143 patients qualified for analysis, with 107 patients having residual tumor diameters ≤1.5 cm. Median follow-up was 24.0 months. Median survival or patients without residual enhancing tumor exceeded the follow-up period. Median survival was 16.9 months for 32 patients with residual tumor diameters >0 to ≤1.5 cm (95% CI: 13.3–20.5, p = 0.039), and 13.9 months (10.3–17.5, overall p < 0.001) for 36 patients with residual tumor diameters >1.5 cm. Patient age at diagnosis and extent of resection were independently associated with survival. Patients with MGMT promoter methylated tumors and complete resection made the best prognosis. Completeness of resection acts synergistically with concomitant and adjuvant radiochemotherapy, especially in patients with MGMT promoter methylation

    Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

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    B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a common marmoset (Callithrix jacchus) model of experimental autoimmune encephalomyelitis (EAE). A MS-like disease was induced by immunization with recombinant human myelin/oligodendrocyte glycoprotein (rhMOG) in complete Freund's adjuvant. The results show that the anti-BLyS and anti-APRIL antibody cause significant depletion of circulating CD20+ B cells, but a small subset of CD20 + CD40highB cells was not depleted. Induction of CD20+ B cell depletion from lymph nodes was only observed in the anti-BLyS treated monkeys. Both antibodies had a significant inhibitory effect on disease development, but all monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were sacrificed with the same clinical signs as saline-treated monkeys, but nevertheless displayed significantly reduced spinal cord demyelination. This effect was not observed in the anti-APRIL treated monkeys. The two antibodies had a different effect on T cell subset activation and the profiles of ex vivo released cytokines. In conclusion, treatment with anti-BLyS and anti-APRIL delays the development of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms

    Development of a tablet application for the screening of receptive vocabulary skills in multilingual children: A pilot study

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    For professionals working with multi-lingual children, detecting language deficits in a child’s home language can present a challenge. This is largely due to the scarcity of standardised assessments in many children’s home languages and missing normative data on multilingual language acquisition. A common approach is to translate existing English language vocabulary measures into other languages. However, this approach does not take into account the cultural and linguistic differences between languages. This pilot study explored whether English and home language receptive vocabulary skills can be objectively and reliably screened using a tablet application. Preliminary data on mono- and multilingual vocabulary skills was collected from 139 children aged 6-7 years. A tablet application was designed to assess children’s receptive vocabulary in both English, and an additional eight languages using a four choice picture paradigm. Linguistically controlled and pre-recorded target items are presented orally via the tablet in each language and responses are made via the touchscreen and automatically scored. The English version of the test was administered to 67 mono- and 72 multilingual children, while 38 multilingual children also completed the test in their home language. Test criteria measures, including reliability and concurrent validity showed satisfactory results. These findings suggest that the tablet application could be a useful tool for professionals to screen receptive vocabulary skills in mono- and multilingual children. Limitations of the first version of the RVS and future steps are discussed

    Careers in ecstasy use: do ecstasy users cease of their own accord? Implications for intervention development

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    <p>Abstract</p> <p>Background</p> <p>Ecstasy (MDMA, 3, 4-methylenodioxymethamphetamine) use is widespread in the Netherlands, with a lifetime prevalence of 4.3%, and two-thirds of dance party visitors being ecstasy users. However, research into Dutch ecstasy use patterns is lacking. In addition, recent studies suggest that ecstasy users cease their use automatically, which implies that interventions would do better to better focus on the promotion of harm reduction strategies than on inducing cessation. The current study addresses this process of ecstasy cessation.</p> <p>Methods</p> <p>32 participants from the Dutch dance scene were interviewed, and the results were systematically analysed using NVivo.</p> <p>Results</p> <p>Most ecstasy users had started to use out of curiosity. During use, users applied a host of harm reduction strategies, albeit inconsistently and sometimes incorrectly. Most users appeared to cease ecstasy use automatically because of loss of interest or changing life circumstances (e.g. a new job or relationship).</p> <p>Conclusion</p> <p>It appears that cessation of ecstasy use is largely determined by environmental variables and not by health concerns. This supports the idea that health promotion resources are better spent in trying to promote consistent and correct application of harm reduction practices than in trying to induce cessation.</p

    The Relevance of Fatalism in the Study of Latinas’ Cancer Screening Behavior: A Systematic Review of the Literature

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    # The Author(s) 2010. This article is published with open access at Springerlink.com Background Fatalism has been identified as a dominant belief among Latinos and is believed to act as a barrier to cancer prevention. However, controversy exists over the utility of the construct in explaining health disparities experienced by disadvantaged populations above the influence of structural barriers such as low socioeconomic status (SES) and limited access to health care. Purpose This paper reviews the empirical research on fatalism and Latinas ’ participation in cancer screening in an attempt to determine whether fatalism predicts participation in cancer screening after accounting for structural barriers
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