2,745 research outputs found
Signal transducer and activator of transcription 3 (STAT3) controls susceptibility to Epstein-Barr virus reactivation in B cells
Colloidal stabilization via nanoparticle haloing
We present a detailed numerical study of effective interactions between
micron-sized silica spheres, induced by highly charged zirconia nanoparticles.
It is demonstrated that the effective interactions are consistent with a
recently discovered mechanism for colloidal stabilization. In accordance with
the experimental observations, small nanoparticle concentrations induce an
effective repulsion that counteracts the intrinsic van der Waals attraction
between the colloids and thus stabilizes the suspension. At higher nanoparticle
concentrations an attractive potential is recovered, resulting in reentrant
gelation. Monte Carlo simulations of this highly size-asymmetric mixture are
made possible by means of a geometric cluster Monte Carlo algorithm. A
comparison is made to results obtained from the Ornstein-Zernike equations with
the hypernetted-chain closure
Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC50 values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC50 values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC50 of 75 µM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine
Trajectories of Pain and Function after Primary Hip and Knee Arthroplasty:The ADAPT Cohort Study
BACKGROUND AND PURPOSE:Pain and function improve dramatically in the first three months after hip and knee arthroplasty but the trajectory after three months is less well described. It is also unclear how pre-operative pain and function influence short- and long-term recovery. We explored the trajectory of change in function and pain until and beyond 3-months post-operatively and the influence of pre-operative self-reported symptoms. METHODS:The study was a prospective cohort study of 164 patients undergoing primary hip (n = 80) or knee (n = 84) arthroplasty in the United Kingdom. Self-reported measures of pain and function using the Western Ontario and McMaster Universities Osteoarthritis index were collected pre-operatively and at 3 and 12 months post-operatively. Hip and knee arthroplasties were analysed separately, and patients were split into two groups: those with high or low symptoms pre-operatively. Multilevel regression models were used for each outcome (pain and function), and the trajectories of change were charted (0-3 months and 3-12 months). RESULTS:Hip: Most improvement occurred within the first 3 months following hip surgery and patients with worse pre-operative scores had greater changes. The mean changes observed between 3 and twelve months were statistically insignificant. One year after surgery, patients with worse pre-operative scores had post-operative outcomes similar to those observed among patients with less severe pre-operative symptoms. Knee: Most improvement occurred in the first 3 months following knee surgery with no significant change thereafter. Despite greater mean change during the first three months, patients with worse pre-operative scores had not 'caught-up' with those with less severe pre-operative symptoms 12 months after their surgery. CONCLUSION:Most symptomatic improvement occurred within the first 3 months after surgery with no significant change between 3-12 months. Further investigations are now required to determine if patients with severe symptoms at the time of their knee arthroplasty have a different pre-surgical history than those with less severe symptoms and if they could benefit from earlier surgical intervention and tailored rehabilitation to achieve better post-operative patient-reported outcomes
Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults
<p>Abstract</p> <p>Background</p> <p>Supplemental vitamin D modulates inflammatory cytokines and skeletal muscle function, but results are inconsistent. It is unknown if these inconsistencies are dependent on the supplemental dose of vitamin D. Therefore, the purpose of this study was to identify the influence of different doses of supplemental vitamin D on inflammatory cytokines and muscular strength in young adults.</p> <p>Methods</p> <p>Men (<it>n </it>= 15) and women (<it>n </it>= 15) received a daily placebo or vitamin D supplement (200 or 4000 IU) for 28-d during the winter. Serum 25-hydroxyvitamin D (25(OH)D), cytokine concentrations and muscular (leg) strength measurements were performed prior to and during supplementation. Statistical significance of data were assessed with a two-way (time, treatment) analysis of variance (ANOVA) with repeated measures, followed by a Tukey's Honestly Significant Difference to test multiple pairwise comparisons.</p> <p>Results</p> <p>Upon enrollment, 63% of the subjects were vitamin D sufficient (serum 25(OH)D ≥ 30 ng/ml). Serum 25(OH)D and interleukin (IL)-5 decreased (<it>P </it>< 0.05) across time in the placebo group. Supplemental vitamin D at 200 IU maintained serum 25(OH)D concentrations and increased IL-5 (<it>P </it>< 0.05). Supplemental vitamin D at 4000 IU increased (<it>P </it>< 0.05) serum 25(OH)D without altering IL-5 concentrations. Although serum 25(OH)D concentrations correlated (<it>P </it>< 0.05) with muscle strength, muscle strength was not changed by supplemental vitamin D.</p> <p>Conclusion</p> <p>In young adults who were vitamin D sufficient prior to supplementation, we conclude that a low-daily dose of supplemental vitamin D prevents serum 25(OH)D and IL-5 concentration decreases, and that muscular strength does not parallel the 25(OH)D increase induced by a high-daily dose of supplemental vitamin D. Considering that IL-5 protects against viruses and bacterial infections, these findings could have a broad physiological importance regarding the ability of vitamin D sufficiency to mediate the immune systems protection against infection.</p
Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement:The APEX randomised controlled trials
Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: −0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR
The Atacama Cosmology Telescope: A Measurement of the Thermal Sunyaev-Zel'dovich Effect Using the Skewness of the CMB Temperature Distribution
We present a detection of the unnormalized skewness induced by the
thermal Sunyaev-Zel'dovich (tSZ) effect in filtered Atacama Cosmology Telescope
(ACT) 148 GHz cosmic microwave background temperature maps. Contamination due
to infrared and radio sources is minimized by template subtraction of resolved
sources and by constructing a mask using outlying values in the 218 GHz
(tSZ-null) ACT maps. We measure = -31 +- 6 \mu K^3 (measurement error
only) or +- 14 \mu K^3 (including cosmic variance error) in the filtered ACT
data, a 5-sigma detection. We show that the skewness is a sensitive probe of
sigma_8, and use analytic calculations and tSZ simulations to obtain
cosmological constraints from this measurement. From this signal alone we infer
a value of sigma_8= 0.79 +0.03 -0.03 (68 % C.L.) +0.06 -0.06 (95 % C.L.). Our
results demonstrate that measurements of non-Gaussianity can be a useful method
for characterizing the tSZ effect and extracting the underlying cosmological
information.Comment: 9 pages, 5 figures. Replaced with version accepted by Phys. Rev. D,
with improvements to the likelihood function and the IR source treatment;
only minor changes in the result
Computing prime factors with a Josephson phase qubit quantum processor
A quantum processor (QuP) can be used to exploit quantum mechanics to find
the prime factors of composite numbers[1]. Compiled versions of Shor's
algorithm have been demonstrated on ensemble quantum systems[2] and photonic
systems[3-5], however this has yet to be shown using solid state quantum bits
(qubits). Two advantages of superconducting qubit architectures are the use of
conventional microfabrication techniques, which allow straightforward scaling
to large numbers of qubits, and a toolkit of circuit elements that can be used
to engineer a variety of qubit types and interactions[6, 7]. Using a number of
recent qubit control and hardware advances [7-13], here we demonstrate a
nine-quantum-element solid-state QuP and show three experiments to highlight
its capabilities. We begin by characterizing the device with spectroscopy.
Next, we produces coherent interactions between five qubits and verify bi- and
tripartite entanglement via quantum state tomography (QST) [8, 12, 14, 15]. In
the final experiment, we run a three-qubit compiled version of Shor's algorithm
to factor the number 15, and successfully find the prime factors 48% of the
time. Improvements in the superconducting qubit coherence times and more
complex circuits should provide the resources necessary to factor larger
composite numbers and run more intricate quantum algorithms.Comment: 5 pages, 3 figure
Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM):pragmatic, parallel group, open label, randomised controlled trial
OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Unknow
Infection after total joint replacement of the hip and knee:research programme including the INFORM RCT
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