248 research outputs found

    Detection and characterization of leukemic stem cells

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    Effect of methamphetamine dependence on inhibitory deficits in a novel human open-field paradigm.

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    RationaleMethamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions.ObjectivesIn the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology.ResultsMA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year.ConclusionsAbstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population

    К численному решению задач о деформации анизотропных пластин с отверстием

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    Представлен подход к расчету напряженно-деформированного состояния пластин с отверстием, основанный на численной параметризации двусвязной области, сведении исходной нелинейной краевой задачи к последовательности линейных двухмерных и интегрировании последних устойчивым численным методом. Исследуется влияние формы и месторасположения отверстия на напряженно-деформированное состояние квадратной пластины.Представлено підхід до розрахунку напружено-деформованого стану пластин, що послаблені отвором. Підхід базується на числовій параметризації двозв’язної області, зведенні вихідної нелінійної задачі до послідовності лінійних двомірних та останніх до одномірних, інтегрування яких проводиться стійким числовим методом. Досліджується вплив форми та місцезнаходження отвору на напружено-деформований стан квадратної пластини.The study presents an approach to stressed-state analysis of plates with apertures which is based on the numerical parameterization of a doubly-connected area, reduction of the initial nonlinear boundary-value problem to a sequence of linear two-dimensional problems and integrating the latter by the stable numerical method. The effect of form and place of an aperture on stressed state of a square plate has been analyzed

    Sustainable employability of teachers with hearing loss

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    Objective In many countries the retirement age is rising. Consequently, age-related hearing loss is an increasing occupational health problem. This study examined the association between hearing loss and sustainable employability of teachers. Design For this cross-sectional study a survey and an online hearing screening test were used. Sustainable employability was measured with the Capability Set for Work Questionnaire (CSWQ), examining seven work values. CSWQ-scores of teachers with poor, insufficient, and good hearing were investigated with ordinal regression analyses. Work values and discrepancies between the importance and achievement of the values were examined by chi-square tests. Study sample Dutch teachers (N = 737) of whom 146 (20%) had insufficient and 86 (12%) poor hearing. Results Teachers with insufficient (OR = 0.64; 95% CI 0.46–0.89) and poor (OR = 0.55; 95% CI 0.36–0.83) hearing had lower CSWQ-scores compared with good hearing teachers. Adjustment for covariates, in particular for self-rated health, attenuated the associations. Compared with good hearing teachers, teachers with poor hearing reported more discrepancies in using their knowledge and skills and setting their own goals at work. Conclusions Hearing loss was negatively associated with sustainable employability of teachers. This emphasises the importance of assessing the hearing status of teachers

    Focus Group Study Exploring Factors Related to Frequent Sickness Absence

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    INTRODUCTION:Research investigating frequent sickness absence (3 or more episodes per year) is scarce and qualitative research from the perspective of frequent absentees themselves is lacking. The aim of the current study is to explore awareness, determinants of and solutions to frequent sickness absence from the perspective of frequent absentees themselves. METHODS:We performed a qualitative study of 3 focus group discussions involving a total of 15 frequent absentees. Focus group discussions were audiotaped and transcribed verbatim. Results were analyzed with the Graneheim method using the Job Demands Resources (JD-R) model as theoretical framework. RESULTS:Many participants were not aware of their frequent sickness absence and the risk of future long-term sickness absence. As determinants, participants mentioned job demands, job resources, home demands, poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Managing these factors and improving communication (skills) were regarded as solutions to reduce frequent sickness absence. CONCLUSIONS:The JD-R model provided a framework for determinants of and solutions to frequent sickness absence. Additional determinants were poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Frequent sickness absence should be regarded as a signal that something is wrong. Managers, supervisors, and occupational health care providers should advise and support frequent absentees to accommodate job demands, increase both job and personal resources, and improve health rather than express disapproval of frequent sickness absence and apply pressure regarding work attendance

    Cardio-oncology: an overview on outpatient management and future developments

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    Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients. Progression to overt heart failure carries a strikingly poor prognosis with a 2-year mortality rate of 60%. Early detection of left ventricular damage by periodic monitoring and prompt initiation of heart failure treatment is key in improving cardiovascular prognosis. To meet the growing demand for a specialised interdisciplinary approach for the prevention and management of cardiovascular complications induced by cancer treatment, a new discipline termed cardio-oncology has evolved. However, an uniform, multidisciplinary approach is currently lacking in the Netherlands. This overview provides an introduction and comprehensive summary of this emerging discipline and offers a practical strategy for the outpatient management of this specific patient population

    Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines

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    Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines
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