326 research outputs found

    Carrot and Stick: How Reemployment Bonuses and Benefit Sanctions Affect Job Finding Rates

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    To increase their transition from welfare to work, benefit recipients in the municipality of Rotterdam were exposed to various financial incentives, including both carrots to sticks. Once their benefit spell exceeded one year, welfare recipients were entitled to a reemployment bonus if they found a job that lasted at least six months. However, they could also be punished for noncompliance with eligibility requirements and face a sanction, i.e. a temporary reducing of their benefits. In this paper we investigate how benefit sanctions and reemployment bonuses affect job finding rates of welfare recipients. We find that benefit sanctions were effective in bringing unemployed from welfare to work more quickly while reemployment bonuses were not.welfare to work, financial incentives, timing-of-events, dynamic selection

    Acta societatis pro fauna et flora Fennica 67

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    Kielet ruotsi ja saksa

    Divergent effects of central melanocortin signalling on fat and sucrose preference in humans.

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    Melanocortin-4-receptor (MC4R)-expressing neurons modulate food intake and preference in rodents but their role in human food preference is unknown. Here we show that compared with lean and weight-matched controls, MC4R deficient individuals exhibited a markedly increased preference for high fat, but a significantly reduced preference for high sucrose food. These effects mirror those in Mc4r null rodents and provide evidence for a central molecular circuit influencing human macronutrient preference.This work was supported by the Wellcome Trust (to A.A.v.d.K., P.C.F., I.S.F.), the National Institute for Health Research Cambridge Biomedical Research Centre (to S.O’R., I.S.F.), the Bernard Wolfe Health Neuroscience Fund (to A.A.v.d.K., I.S.F., P.C.F.) and the European Research Council (I.S.F.). This work was supported by the NeuroFAST consortium which is funded by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no 245009.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1305

    Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

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    The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment

    Head-and-neck paragangliomas are associated with sleep-related complaints, especially in the presence of carotid body tumors

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    Item does not contain fulltextOBJECTIVES: The carotid body functions as a chemoreceptor. We hypothesized that head-and-neck paragangliomas (HNP) may disturb the function of these peripheral chemoreceptors and play a role in sleep-disordered breathing. DESIGN: This is a case-control study. SETTING: This study was conducted in a tertiary referral center. PARTICIPANTS AND MAIN OUTCOME MEASURES: We assessed fatigue, sleep, and exercise capacity in 74 HNP patients using three questionnaires (Epworth Sleepiness Scale, St. George Respiratory Questionnaire, and a standard clinical sleep assessment questionnaire). Outcomes were compared to those of age- and sex-matched controls. RESULTS AND CONCLUSIONS: Activity, disturbance of psychosocial function, and total score were worse compared to controls (15.4 +/- 18.5 vs. 7.2 +/- 9.9, P = 0.007; 5.3 +/- 10.5 vs. 1.2 +/- 2.6, P = 0.008; and 10.4 +/- 12.9 vs. 5.0 +/- 4.8, P = 0.006, respectively). Patients reported more daytime fatigue, concentration difficulties, and depression (51% vs. 24%, P = 0.006; 31% vs. 10%, P = 0.010; and 19% vs. 2%, P = 0.012). Waking up was reported to be less refreshing in HNP patients (53% vs. 73%, P = 0.038). Dysphonia was a predictor of symptoms, activity, disturbance of psychosocial function, and total scores. Remarkably, the presence of a carotid body tumor was an independent predictor of increased daytime sleepiness (beta = 0.287, P = 0.029). In conclusion, patients with HNP have remarkable sleep-related complaints. Especially the presence of carotid body tumors appears to be associated with increased daytime somnolence.1 juni 201

    Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

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    SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis.National Health and Medical Research Council of Australia (Grant IDs: 1037746, 1003139, 1022684), Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (Grant ID: CE110001021), Royal Australasian College of Physicians (PhD scholar), MND Australia (PhD scholar), Wellcome Trust, Medical Research Council, European Research Council, National Institute for Health Research Cambridge Biomedical Research Centre, The Bernard Wolfe Endowment, Swiss National Science Foundation (Grant IDs: PBLAP3-145870, P3SMP3-155318)This is the author accepted manuscript. The final version is available from Oxford University Press via https://doi.org/10.1093/brain/aww26

    How to Stimulate Single Mothers on Welfare to Find a Job: Evidence from a Natural Experiment

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    We present the results from a natural experiment in which single mothers on welfare were stimulated to find a job. Two policy instruments were introduced: an earnings disregard and job creation. The experiment was performed at the level of municipalities in The Netherlands, a country with relatively high benefits and low incentives for single mothers to leave welfare for work. In our analysis, we make a distinction between native and immigrant welfare recipients. For immigrant single mothers and some groups of native single mothers we find a positive employment effect of an earnings disregard. Job creation in addition to the earnings disregard increased working hours for some groups of single mothers. Although the outflow from welfare was not affected, welfare expenditures were reduced

    KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.

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    Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.This work was supported by the Wellcome Trust (098497/Z/12/Z; 077016/Z/05/Z; 096106/Z/11/Z) (ISF and LRP), Medical Research Council (MC_U106179471) (NW), NIHR Cambridge Biomedical Research Centre (ISF, IB and SOR), and European Research Council (ISF). This study makes use of data generated by the UK10K Consortium (WT091310). A full list of the investigators who contributed to the generation of the data is available from http://www.UK10K.org.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2813%2901276-2
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