Quantitative sensory testing (QST) is an instrument to assess positive and negative sensory signs, helping to identify mechanisms underlying pathologic pain conditions. In this study, we evaluated ...the test-retest reliability (TR-R) and the interobserver reliability (IO-R) of QST in patients with sensory disturbances of different etiologies. In 4 centres, 60 patients (37 male and 23 female, 56.4±1.9years) with lesions or diseases of the somatosensory system were included. QST comprised 13 parameters including detection and pain thresholds for thermal and mechanical stimuli. QST was performed in the clinically most affected test area and a less or unaffected control area in a morning and an afternoon session on 2 consecutive days by examiner pairs (4 QSTs/patient). For both, TR-R and IO-R, there were high correlations (r=0.80-0.93) at the affected test area, except for wind-up ratio (TR-R: r=0.67; IO-R: r=0.56) and paradoxical heat sensations (TR-R: r=0.35; IO-R: r=0.44). Mean IO-R (r=0.83, 31% unexplained variance) was slightly lower than TR-R (r=0.86, 26% unexplained variance, P<.05); the difference in variance amounted to 5%. There were no differences between study centres. In a subgroup with an unaffected control area (n=43), reliabilities were significantly better in the test area (TR-R: r=0.86; IO-R: r=0.83) than in the control area (TR-R: r=0.79; IO-R: r=0.71, each P<.01), suggesting that disease-related systematic variance enhances reliability of QST. We conclude that standardized QST performed by trained examiners is a valuable diagnostic instrument with good test-retest and interobserver reliability within 2days. With standardized training, observer bias is much lower than random variance. Quantitative sensory testing performed by trained examiners is a valuable diagnostic instrument with good interobserver and test-retest reliability for use in patients with sensory disturbances of different etiologies to help identify mechanisms of neuropathic and non-neuropathic pain.
Most studies using gas permeation to characterize physical aging in thin polymer films have focused on polymers of interest as membrane materials, such as polysulfone (PSF) and Matrimid. Many other ...physical aging studies, using techniques other than gas permeation, focus on polystyrene (PS). In this work, physical aging in bulk PS films and PDMS-coated thin PS films was studied using well-established gas permeation techniques. The ∼400 nm PS films aged slightly faster than bulk PS. However, the difference between rates of aging in thin and thick films was much less than that reported in PSF and Matrimid films of similar thicknesses. The ∼800 nm films aged in a manner generally similar to bulk PS. Comparison of the normalized oxygen permeability of ∼400 nm films of PS, PSF, and Matrimid revealed that a ∼400 nm PS film experiences a slower decline in relative permeability than a PSF or Matrimid film does. Unlike what has been observed previously in studies of PSF and Matrimid films, PS films do not appear to show aging behavior that is strongly dependent on film thickness or highly accelerated relative to bulk. Because it would be difficult to use the results of PS aging studies to predict the aging behavior of typical gas separation polymers, we suggest that PS is not a good model for the aging behavior of commercially useful gas separation membrane materials.
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Evidence for age-related effects on wound healing have been derived for the most part from empirical observations without adjustment for confounders other than age. Age-related changes in the ...structure and function of the skin do occur. Some of these changes result from chronic solar radiation exposure rather than chronological age per se. The tensile strength of wounds, accumulation of wound healing factors and rate of wound closure have all been examined in relation to chronological aging. However, the clinical impact of these changes in acute wound healing appears to be small. Poor healing in chronic wounds is more often related to comorbid conditions rather than age alone. Since the majority of these chronic wounds occur in elderly populations, this has contributed to the conclusion that aging itself may influence healing. Progress in understanding the role that growth factors play in wound healing and the ability to synthesise adequate quantities of these factors for clinical use has led to clinical trials evaluating their use in wound healing. The results of these studies, with the possible exception of those in diabetic wounds, have been disappointing. Insight into the wound healing process indicates that growth factors interact during wound healing in a sequential and orderly process. Improved wound healing may require different clinical designs or the use of these factors in a precisely timed sequential administration.
The role of the immune system in schizophrenia remains controversial despite numerous studies to date. Most studies have profiled expression of select genes or proteins in peripheral blood, but none ...have focused on the expression of canonical pathways that mediate overall immune response. The current study used a systematic genetic approach to investigate the role of the immune system in a large sample of post-mortem brain of patients with schizophrenia: RNA sequencing was performed to assess the differential expression of 561 immune genes and 20 immune pathways in dorsolateral prefrontal cortex (DLPFC) (144 schizophrenia and 196 control subjects) and hippocampus (83 schizophrenia and 187 control subjects). The effect of RNA quality on gene expression was found to be highly correlated with the effect of diagnosis even after adjustment for observable RNA quality parameters (i.e. RNA integrity), thus this confounding relationship was statistically controlled using principal components derived from the gene expression matrix. In DLPFC, 23 immune genes were found to be differentially expressed (false discovery rate <0.05), of which seven genes replicated in both directionality and at nominal significance (P<0.05) in an independent post-mortem DLPFC data set (182 schizophrenia and 212 control subjects), although notably at least five of these genes have prominent roles in pathways other than immune function and overall the effect sizes were minimal (fold change <1.1). In the hippocampus, no individual immune genes were identified to be differentially expressed, and in both DLPFC and hippocampus none of the individual immune pathways were relatively differentially expressed. Further, genomic schizophrenia risk profiles scores were not correlated with the expression of individual immune pathways or differentially expressed genes. Overall, past reports claiming a primary pathogenic role of the immune system intrinsic to the brain in schizophrenia could not be confirmed.
Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or ...surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids.
All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse.
Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) responded to steroids. Admission C-reactive protein (CRP) (P = 0.009, odds ratio OR 1.006), albumin (P < 0.001, OR 0.894) and endoscopic severity (P < 0.001, OR 3.166) differed significantly between responders and nonresponders. A simple UC severity score (area under the curve AUC 0.754, P < 0.001) was derived from these variables; 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician's global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value PPV 78.1%, negative predictive value NPV 87.1%).
More than three quarters of patients scoring 3 (albumin ≤30 g/L, CRP ≥50 mg/L, and increased endoscopic severity) did not respond to IV steroids. This combination of parameters (ACE) identifies on admission a high-risk population who may benefit from earlier second-line medical treatment or surgical intervention.
In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women ...who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.
Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.
In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.
Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
The deregulated electricity market calls for robust optimal power flow (OPF) tools that can provide a) deterministic convergence; b) accurate computation of nodal prices; c) support of both smooth ...and nonsmooth costing of a variety of resources and services, such as real energy, reactive energy, voltages support, etc.; d) full active and reactive power flow modeling of large-scale systems; and e) satisfactory worst-case performance that meets the real-time dispatching requirement. Most prior research on OPF has focused on performance issues in the context of regulated systems, without giving much emphasis to requirements a)-c). This paper discusses the computational challenges brought up by the deregulation and attempts to address them through the introduction of new OPF formulations and algorithms. Trust-region- based augmented Lagrangian method (TRALM), step-controlled primal-dual interior point method (SCIPM), and constrained cost variable (CCV) OPF formulation are proposed. The new formulations and algorithms, along with several existing ones, are tested and compared using large-scale power system models.
At-sea movements and activity patterns of brown skuas Stercorarius antarcticus lonnbergi from South Georgia were analysed in 2 winters, a decade apart, to examine the degree of consistency in ...migration strategies and habitat preferences during the non-breeding and prelaying exodus periods. Oceanographic habitat preferences of tracked skuas were determined using a robust model accounting for availability. At the population level, brown skuas were broadly consistent in their choice of wintering areas and habitat preferences, although the distribution extended farther east in 2012 than in 2002. Skuas preferred areas associated with static oceanography (bathymetric features) both during the non-breeding and pre-laying periods, which may explain the consistency between years in habitat use. There was no significant effect of year on departure dates from South Georgia, but birds returned earlier to the colony in 2002. Migration schedules varied according to breeding status, with failed birds departing earlier than birds that bred successfully. Although failed birds travelled farther from the colony, there was little variation in dates of return. In general the timing of movements was similar between sexes, but females were more likely than males to engage in a pre-laying exodus. Brown skuas spent a much higher proportion of time sitting on the water than other seabirds during both the non-breeding and prelaying exodus periods, and the number of flight bouts per day was surprisingly low. The selection of static features by brown skuas may indicate that skuas may have less flexibility to track environmental changes than species that use dynamic cues.
Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated ...prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.
In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival.
The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001).
The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).
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