A series of cryogenic, layered deuterium-tritium (DT) implosions have produced, for the first time, fusion energy output twice the peak kinetic energy of the imploding shell. These experiments at the ...National Ignition Facility utilized high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums, resulting in a peak hohlraum radiative temperature ∼290 eV. The imploding shell, composed of the nonablated high density carbon and the DT cryogenic layer, is, thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic energy of ∼21 kJ, which once stagnated produced a total DT neutron yield of 1.9×10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ. Time dependent low mode asymmetries that limited further progress of implosions have now been controlled, leading to an increased compression of the hot spot. It resulted in hot spot areal density (ρr∼0.3 g/cm^{2}) and stagnation pressure (∼360 Gbar) never before achieved in a laboratory experiment.
In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, ...dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the “four D’s” of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are “When to start intravenous fluids?”, “When to stop intravenous fluids?”, “When to start de-resuscitation or active fluid removal?” and finally “When to stop de-resuscitation?” In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.
Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of ...these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA).
Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately.
Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities.
Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.
1 MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK
2 Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, USA
3 Twincore ...Center for Experimental and Clinical Infection Research, Department of Experimental Virology, Hannover, Germany
4 Helmholtz Center for Infection Research, Braunschweig, Germany
5 Medizinische Hochschule Hannover, Germany
6 Okairòs-Ceinge, Naples, Italy
7 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
Correspondence Arvind H. Patel a.patel{at}mrcvu.gla.ac.uk
Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1 E1E2 -transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1 W529A was unaffected by the presence of neutralizing antibodies that inhibit E2–CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission.
Published online ahead of print on 3 October 2008 as DOI 10.1099/vir.0.2008/006700-0.
Supplementary material is available with the online version of this paper.
Persistent postoperative pain (PPP) is common after total knee arthroplasty (TKA). The primary aim of this prospective cohort study was to identify important predictors of moderate to severe PPP 6 ...and 12 months after TKA.
Consenting patients (n=300) undergoing primary unilateral TKA attended a preoperative session to collect clinical information (age, gender, BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and psychological variables (depression, anxiety, catastrophising, expected pain). Quantitative sensory testing (pressure pain thresholds, temporal summation, conditioned pain modulation) was performed, and blood samples were obtained for subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at rest and during movement. Surgical factors (surgery time, patella resurfacing, anaesthetic type) were collected after operation. Follow-up questionnaires were sent 6 and 12 months after surgery. Multivariate logistic regression was used to identify predictors of PPP.
The prevalence of moderate to severe PPP was 21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60% (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of preoperative pain intensity, expected pain, trait anxiety, and temporal summation (Akaike information criterion, 309.9; area under receiver operating characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative pain intensity, expected pain, and trait anxiety (Akaike information criterion, 286.8; area under ROC curve, 0.66) correctly classified 66% of patients.
Findings from this study highlight several factors that may be targeted in future intervention studies to reduce the development of PPP.
ACTRN12612001089820.
Producing a burning plasma in the laboratory has been a long-standing milestone for the plasma physics community. A burning plasma is a state where alpha particle deposition from deuterium-tritium ...(DT) fusion reactions is the leading source of energy input to the DT plasma. Achieving these high thermonuclear yields in an inertial confinement fusion (ICF) implosion requires an efficient transfer of energy from the driving source, e.g., lasers, to the DT fuel. In indirect-drive ICF, the fuel is loaded into a spherical capsule which is placed at the center of a cylindrical radiation enclosure, the hohlraum. Lasers enter through each end of the hohlraum, depositing their energy in the walls where it is converted to x-rays that drive the capsule implosion. Maintaining a spherically symmetric, stable, and efficient drive is a critical challenge and focus of ICF research effort. Our program at the National Ignition Facility has steadily resolved challenges that began with controlling ablative Rayleigh-Taylor instability in implosions, followed by improving hohlraum-capsule x-ray coupling using low gas-fill hohlraums, improving control of time-dependent implosion symmetry, and reducing target engineering feature-generated perturbations. As a result of this program of work, our team is now poised to enter the burning plasma regime.
Background
While promising, there are mixed findings for the efficacy of transcranial direct current stimulation (tDCS) for the management of chronic pain. The goal of this study was to evaluate the ...effect of anodal tDCS on pain and function in people with upper limb neuropathic pain.
Methods
The study was a double‐blinded, randomized controlled trial. Thirty participants were randomly allocated into active and sham tDCS groups. Baseline assessments of pain and function, as well as quantitative sensory testing (QST) to probe the function of the nociceptive system, were undertaken prior to participants receiving 5 days of active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome measures were re‐assessed 1, 3 and 8 weeks following the intervention.
Results
Group analyses revealed no significant improvement in pain, function, or QST measures over time in either group. However, there were significantly more individual responders (≥30% change in pain) in the active compared to the sham tDCS group at the final follow‐up. In the active group, there was a significant correlation indicating those with higher baseline pain had greater pain relief.
Conclusions
On group analyses, no evidence was provided that 1 mA tDCS is beneficial for people with upper limb neuropathic pain, although it may provide lasting pain relief for some individuals.
Significance
At the group level, we found no evidence that 5 days of active 1 mA tDCS is effective for people with upper limb neuropathic pain. However, there were more individual responders in the active tDCS group compared to sham, and those who responded early after treatment experienced sustained pain relief.
Summary
Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was ...performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty‐nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre‐operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9–5.4)). The median (IQR range) oral morphine equivalent daily dose was 3.6 (0.9–10.5 0–100.0) mg pre‐operatively, 35.0 (22.5–52.5 4.6–180.0) mg in hospital, 12.8 (5.1–24.8 0–57.9) mg from discharge to 3 months and 5.9 (4.5–12.0 0–44.5) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65–1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99–1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre‐operative quantitative sensory testing results or psychological distress. Pre‐operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.
We examined the social network composition among newly homeless youth over time and assessed how pro-social and problematic peers affected sexual and drug-using HIV/AIDS risk-behaviours among 183 ...youth in Los Angeles County, California. The percentage of newly homeless youth who reported that 'most' or 'all' of their friends were attending school, had jobs, and got along with their families was 73%, 24%, and 50% respectively. Logistic regression models indicated that presence of these pro-social peers reduced HIV risk behaviours at two years; odds of HIV-risk were lower with a greater number of peers who attend school, have a job, or have positive family relationships or if networks change over time to include more of these peers. Presence of problematic peers increased the likelihood of HIV risk-taking; odds of HIV risk behaviours increased with a greater number of peers at baseline who steal, have overdosed, have been arrested, or are in a gang, or if networks change to include more of these peers. Interventions should target newly homeless youth in networks that contain problematic peers, but should strive to harness the naturally occurring pro-social peer influences present in these networks.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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