1,154 research outputs found
Randomized Trial—PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis
Introduction: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life (PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program. Methods: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded. Results: We randomized 379 participants; 335 and 243 patients (EX n = 127; CON n = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: −0.1 to 4.8) arbitrary units (P = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US1092 per participant per year. The number of participants with harms was similar between EX (n = 69) and CON (n = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments. Conclusions: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD
The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.
BACKGROUND: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK.
METHODS: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke’s Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team.
RESULTS: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry.
CONCLUSIONS: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally.
TRIAL REGISTRATION: ISRCTN N83508514; registered on 17 December 2014
Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth
Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins
Deterrence in Cyberspace: An Interdisciplinary Review of the Empirical Literature
The popularity of the deterrence perspective across multiple scientific disciplines has sparked a lively debate regarding its relevance in influencing both offenders and targets in cyberspace. Unfortunately, due to the invisible borders between academic disciplines, most of the published literature on deterrence in cyberspace is confined within unique scientific disciplines. This chapter therefore provides an interdisciplinary review of the issue of deterrence in cyberspace. It begins with a short overview of the deterrence perspective, presenting the ongoing debates concerning the relevance of deterrence pillars in influencing cybercriminals’ and cyberattackers’ operations in cyberspace. It then reviews the existing scientific evidence assessing various aspects of deterrence in the context of several disciplines: criminology, law, information systems, and political science. This chapter ends with a few policy implications and proposed directions for future interdisciplinary academic research
Measurement of the Lambda_b Lifetime in Lambda_b --> J/psi Lambda0 in p-pbar Collisions at sqrt(s)=1.96 TeV
We report a measurement of the Lambda_b lifetime in the exclusive decay
Lambda_b --> J/psi Lambda0 in p-pbar collisions at sqrt(s) = 1.96 TeV using an
integrated luminosity of 1.0 fb^{-1} of data collected by the CDF II detector
at the Fermilab Tevatron. Using fully reconstructed decays, we measure
tau(Lambda_b) = 1.593 ^{+0.083}_{-0.078} (stat.) +- 0.033 (syst.) ps. This is
the single most precise measurement of tau(Lambda_b) and is 3.2 sigma higher
than the current world average.Comment: 7 Pages, 2 Figures, 1 Table. Submitted to Phys. Rev. Let
Precision measurement of the top quark mass from dilepton events at CDF II
We report a measurement of the top quark mass, M_t, in the dilepton decay
channel of
using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected
with the CDF II detector. We apply a method that convolutes a leading-order
matrix element with detector resolution functions to form event-by-event
likelihoods; we have enhanced the leading-order description to describe the
effects of initial-state radiation. The joint likelihood is the product of the
likelihoods from 78 candidate events in this sample, which yields a measurement
of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.})
\mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to
publication by journa
Cross Section Measurements of High- Dilepton Final-State Processes Using a Global Fitting Method
We present a new method for studying high- dilepton events
(, , ) and simultaneously
extracting the production cross sections of , , and p\bar{p} \to \ztt at a center-of-mass energy of TeV. We perform a likelihood fit to the dilepton data in a parameter
space defined by the missing transverse energy and the number of jets in the
event. Our results, which use of data recorded with the CDF
II detector at the Fermilab Tevatron Collider, are pb, pb, and
\sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R
Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)
Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions
at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully
reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the
first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) /
B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our
measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23
(syst) improving the statistical uncertainty by more than a factor of two. We
find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs
-> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure
Observation of WZ Production
We report the first observation of the associated production of a W boson and
a Z boson. This result is based on 1.1 fb-1 of integrated luminosity from ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We observe 16 WZ candidates passing our event selection with
an expected background of 2.7 +/- 0.4 events. A fit to the missing transverse
energy distribution indicates an excess of events compared to the background
expectation corresponding to a significance equivalent to six standard
deviations. The measured cross section is sigma(ppbar -> WZ) =
5.0^{+1.8}_{-1.6} pb, consistent with the standard model expectation.Comment: 7 pages, 3 figures. Submitted to Phys. Rev. Let
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