993 research outputs found
The delay-reward heuristic: What do people expect in intertemporal choice tasks?
Recent research has shown that risk and reward are positively correlated in many environments, and that people have internalized this association as a "risk-reward heuristic": when making choices based on incomplete information, people infer probabilities from payoffs and vice-versa, and these inferences shape their decisions. We extend this work by examining people's expectations about another fundamental trade-off-that between monetary reward and delay. In 2 experiments (total N = 670), we adapted a paradigm previously used to demonstrate the risk-reward heuristic. We presented participants with intertemporal choice tasks in which either the delayed reward or the length of the delay was obscured. Participants inferred larger rewards for longer stated delays, and longer delays for larger stated rewards; these inferences also predicted people's willingness to take the delayed option. In exploratory analyses, we found that older participants inferred longer delays and smaller rewards than did younger ones. All of these results replicated in 2 large-scale pre-registered studies with participants from a different population (total N = 2138). Our results suggest that people expect intertemporal choice tasks to offer a trade-off between delay and reward, and differ in their expectations about this trade-off. This "delay-reward heuristic" offers a new perspective on existing models of intertemporal choice and provides new insights into unexplained and systematic individual differences in the willingness to delay gratification
MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients
Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo
Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages
In-stent thrombosis after 68 months of implantation inspite of continuous dual antiplatelet therapy: a case report
Lately, there has been an increased incidence of late stent thrombosis; especially following Drug eluting stent (DES) implantation. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself, patient and lesion characteristics, stent design, and premature cessation of anti-platelet drugs. We present a case of late stent thrombosis (LST) following DES implantation after a period of 68 months, making it the longest reported case of LST reported in the literature, despite the use of dual anti-platelet therapy
Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma
<p>Abstract</p> <p>Background</p> <p>Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.</p> <p>Methods</p> <p>We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.</p> <p>Results</p> <p>From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).</p> <p>Conclusions</p> <p>This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.</p
Design of the DIRECT-project: interventions to increase job resources and recovery opportunities to improve job-related health, well-being, and performance outcomes in nursing homes
Background
Because of high demands at work, nurses are at high risk for occupational burnout and physical complaints. The presence of job resources (such as job autonomy or social support) and recovery opportunities could counteract the adverse effect of high job demands. However, it is still unclear how job resources and recovery opportunities can be translated into effective workplace interventions aiming to improve employee health, well-being, and performance-related outcomes. The aim of the current research project is developing and implementing interventions to optimize job resources and recovery opportunities, which may lead to improved health, well-being and performance of nurses.
Methods/design
The DIRECT-project (DIsc Risk Evaluating Controlled Trial) is a longitudinal, quasi-experimental field study. Nursing home staff of 4 intervention wards and 4 comparison wards will be involved. Based on the results of a base-line survey, interventions will be implemented to optimize job resources and recovery opportunities. After 12 and 24 month the effect of the interventions will be investigated with follow-up surveys. Additionally, a process evaluation will be conducted to map factors that either stimulated or hindered successful implementation as well as the effectiveness of the interventions.
Discussion
The DIRECT-project fulfils a strong need for intervention research in the field of work, stress, performance, and health. The results could reveal (1) how interventions can be tailored to optimize job resources and recovery opportunities, in order to counteract job demands, and (2) what the effects of these interventions will be on health, well-being, and performance of nursing staff
âWhen Helping the Small Hurts the Middleâ: Beer Excise Duties and Market Concentration
The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A
Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa strains with mutation in other flagellar genes, as well as mucoid, nonmotile isolates from cystic fibrosis patients, were also permeabilized by SP-A. Provision of the wild-type fliC gene restored the resistance to SP-A-mediated membrane permeabilization in the fliC-deficient bacteria. In addition, non-mucoid, motile revertants of CF isolates reacquired resistance to SP-A-mediated membrane permeability. Resistance to SP-A was dependent on the presence of an intact flagellar structure, and independent of flagellar-dependent motility. We provide evidence that flagellar-deficient mutants harbor inadequate amounts of LPS required to resist membrane permeabilization by SP-A and cellular lysis by detergent targeting bacterial outer membranes. Thus, the flagellum of P. aeruginosa plays an indirect but important role resisting SP-A-mediated clearance and membrane permeabilization
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of âs = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pTâ„20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60â€pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2â€{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
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