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Selected AbstractsThe response to paired motor cortical stimuli is abolished at a spinal level during human muscle fatigueTHE JOURNAL OF PHYSIOLOGY, Issue 23 2009Chris J. McNeil During maximal exercise, supraspinal fatigue contributes significantly to the decline in muscle performance but little is known about intracortical inhibition during such contractions. Long-interval inhibition is produced by a conditioning motor cortical stimulus delivered via transcranial magnetic stimulation (TMS) 50,200 ms prior to a second test stimulus. We aimed to delineate changes in this inhibition during a sustained maximal voluntary contraction (MVC). Eight subjects performed a 2 min MVC of elbow flexors. Single test and paired (conditioning,test interval of 100 ms) stimuli were delivered via TMS over the motor cortex every 7,8 s throughout the effort and during intermittent MVCs in the recovery period. To determine the role of spinal mechanisms, the protocol was repeated but the TMS test stimulus was replaced by cervicomedullary stimulation which activates the corticospinal tract. TMS motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were recorded from biceps brachii. Unconditioned MEPs increased progressively with fatigue, whereas CMEPs increased initially but returned to the control value in the final 40 s of contraction. In contrast, both conditioned MEPs and CMEPs decreased rapidly with fatigue and were virtually abolished within 30 s. In recovery, unconditioned responses required <30 s but conditioned MEPs and CMEPs required ,90 s to return to control levels. Thus, long-interval inhibition increased markedly as fatigue progressed. Contrary to expectations, subcortically evoked CMEPs were inhibited as much as MEPs. This new phenomenon was also observed in the first dorsal interosseous muscle. Tested with a high intensity conditioning stimulus during a fatiguing maximal effort, long-interval inhibition of MEPs was increased primarily by spinal rather than motor cortical mechanisms. The spinal mechanisms exposed here may contribute to the development of central fatigue in human muscles. [source] The assessment of insulin resistance in manDIABETIC MEDICINE, Issue 7 2002T. M. Wallace Abstract Background Insulin resistance exists when a normal concentration of insulin produces a less than normal biological response. The ability to measure insulin resistance is important in order to understand the aetiopathology of Type 2 diabetes, to examine the epidemiology and to assess the effects of intervention. Methods We assess and compare methods of measurement and have undertaken a literature review from 1966 to 2001. Results Quantitative estimates of insulin resistance can be obtained using model assessments, clamps or insulin infusion sensitivity tests. There is considerable variation in the complexity and labour intensity of the various methods. The most well-established methods are the euglycaemic clamp, minimal model assessment and homeostatic model assessment (HOMA). No single test is appropriate under all circumstances. Conclusions There are a number of well-established tests used to measure insulin resistance: the choice of method depends on the size and type of study to be undertaken. Although the so-called ,gold-standard' test, the euglycaemic clamp, is useful for intensive physiological studies on small numbers of subjects, a simpler tool such as HOMA is more appropriate for large epidemiological studies. It is important to be aware that most techniques measure stimulated insulin resistance whereas HOMA gives an estimate of basal insulin resistance. Caution should be exercised when making comparisons between studies due to variations in infusion protocols, sampling procedures and hormone assays used in different studies. [source] Association tests using kernel-based measures of multi-locus genotype similarity between individualsGENETIC EPIDEMIOLOGY, Issue 3 2010Indranil Mukhopadhyay Abstract In a genetic association study, it is often desirable to perform an overall test of whether any or all single-nucleotide polymorphisms (SNPs) in a gene are associated with a phenotype. Several such tests exist, but most of them are powerful only under very specific assumptions about the genetic effects of the individual SNPs. In addition, some of the existing tests assume that the direction of the effect of each SNP is known, which is a highly unlikely scenario. Here, we propose a new kernel-based association test of joint association of several SNPs. Our test is non-parametric and robust, and does not make any assumption about the directions of individual SNP effects. It can be used to test multiple correlated SNPs within a gene and can also be used to test independent SNPs or genes in a biological pathway. Our test uses an analysis of variance paradigm to compare variation between cases and controls to the variation within the groups. The variation is measured using kernel functions for each marker, and then a composite statistic is constructed to combine the markers into a single test. We present simulation results comparing our statistic to the U -statistic-based method by Schaid et al. ([2005] Am. J. Hum. Genet. 76:780,793) and another statistic by Wessel and Schork ([2006] Am. J. Hum. Genet. 79:792,806). We consider a variety of different disease models and assumptions about how many SNPs within the gene are actually associated with disease. Our results indicate that our statistic has higher power than other statistics under most realistic conditions. Genet. Epidemiol. 34: 213,221, 2010. © 2009 Wiley-Liss, Inc. [source] NBT-PABA test to assess efficiency and kinetics of substituted proteolytic enzyme action in pancreatic duct ligated minipigs,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2008A. Mößeler Summary The NBT-PABA test is an established method for diagnosis of pancreatic exocrine insufficiency. In the present study the NBT-PABA test was used to test and compare the efficacy of two multienzyme preparations (product A and B) differing in galenic preparation in minipigs in which pancreatic exocrine insufficiency (PEI) was induced by pancreatic duct ligation. Without enzyme substitution no distinct increase in PABA was found in blood after oral administration of NBT-PABA. Administration of both enzyme preparations led to a clear dose dependent rise in PABA-concentrations in blood. Interestingly, the two preparations showed different time curves of serum PABA concentration, indicating differences in the kinetic of proteolytic enzyme action. It is concluded that the NBT-PABA test can be a very useful test for indirectly evaluating proteolytic enzyme efficacy in vivo, and also gives information about the kinetics of enzyme action, not only the end-result of enzyme action (like digestibility trials which were used traditionally). A single test is performed in a few hours and there is no need for fistulated animals. [source] S100A8/A9: A Potential New Diagnostic Aid for Acute AppendicitisACADEMIC EMERGENCY MEDICINE, Issue 3 2010John F. Bealer MD Abstract Objectives:, Diagnosing acute appendicitis is a daunting clinical challenge, as there is no single test that reliably distinguishes acute appendicitis from other etiologies of acute abdominal pain. In this study, the authors examined whether circulating levels of S100A8/A9 could be useful as a marker to aid in the diagnosis of acute appendicitis. Methods:, Plasma samples from emergency department (ED) patients with acute abdominal pain (n = 181) were tested using an immunoassay for S100A8/A9. Results:, The sensitivity and specificity for S100A8/A9 in diagnosing acute appendicitis were estimated to be 93% (95% confidence interval [CI] = 81% to 97%) and 54% (95% CI = 45% to 62%), respectively. Negative predictive value (NPV) was 96% (95% CI = 89% to 99%), and positive predictive value (PPV) was 37% (95% CI = 28% to 47%). Performance characteristics of elevated white blood cell (WBC) count were also estimated: sensitivity 63% (95% CI = 47% to 76%), specificity 67% (95% CI = 59% to 75%), NPV 86% (95% CI = 78% to 91%), and PPV 36% (95% CI = 26% to 47%). Conclusions:, This is the first report exploring the relationship between circulating S100A8/A9 and acute appendicitis and establishes proof of concept for this biomarker as a diagnostic test for acute appendicitis. Further studies are indicated to optimize the use of this biomarker, in conjunction with other established approaches. ACADEMIC EMERGENCY MEDICINE 2010; 17:333,336 © 2010 by the Society for Academic Emergency Medicine [source] Sarcoidosis of the skin , A dermatological puzzle: important differential diagnostic aspects and guidelines for clinical and histopathological recognitionJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2010G Tchernev Abstract Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of ,great imitator' and ,clinical chameleon' have long been used. There is, in fact, a large group of skin diseases that can enter the differential diagnosis with cutaneous sarcoid manifestations, either clinically or/and pathologically. As the clinical consequences and the prognosis of these groups of diseases are often very different, it is important to correctly plan the diagnostic workup. The diagnostic process in this case often presents a challenge as no single test is sufficiently specific, so that a certain diagnosis can be only made in the presence of a compatible clinical and radiographic picture, along with histopathological evidence of non-necrotizing, epithelioid cell granulomas, and exclusion of other potential aetiologies. For practical reasons, four main groups of skin conditions capable of mimicking sarcoidosis can be identified: (i) transmissible, infectious diseases; (ii) allergic and immunological manifestations of various aetiologies; (iii) granulomatous diseases of various aetiologies; and (iv) lymphomas and pseudolymphomas. The aim of this article is to describe the main clinical and histopathological findings of such disease entities, and to discuss the role of those features (morphological, pathological and laboratory) that can help distinguish them from sarcoidosis of the skin. [source] MMPI Profile as an Outcome "Predictor" in the Treatment of Noncancer Pain Patients Utilizing Intraspinal Opioid TherapyNEUROMODULATION, Issue 3 2001Daniel M. Doleys PhD Objective. To evaluate changes in Minnesota Multiphasic Personality Inventory (MMPI) profiles pre- and post-treatment involving intrathecal opioid therapy. Patients and Methods. This study reports on 30 patients that were evaluated pre- and post-intraspinal opioid therapy. Treatment duration was slightly more than four years. Each patient experienced chronic non-cancer pain deemed suitable for trialing and subsequent implantation of a drug administration system (DAS). On average the patients had experienced pain for 8.4 years and had a mean of 3.2 pain-related surgeries. Results. The patients could be divided into "positive change group" and "negative change group" based upon pre- and post-treatment MMPI profiles. Those patients in the negative change group had more "normal profiles" pretreatment. This group evidenced less reduction in pain and was found to be using slightly higher levels of intraspinal opioids. Conclusions. These results would suggest that the MMPI profile may not be a good "predictor" of long-term outcome utilizing intraspinal opioid therapy. Indeed, patients with the more normal profile pretreatment did not fare as well as those with the more elevated profile. A positive change in MMPI profile from pre- to post-treatment was associated with a higher level of pain reduction. Patient selection therefore should be based not on a single test such as the MMPI, but on consistency across multiple sources of information including physical examination, complaints of pain and disability, behavioral observations, and psychological testing. [source] Evaluating differences in linkage disequilibrium between populationsANNALS OF HUMAN GENETICS, Issue 3 2010Birgir Hrafnkelsson Summary We propose two methods to evaluate the statistical significance of differences in linkage disequilibrium (LD) between populations, where LD is measured by the standardised parameter D,. The first method is based on bootstrapping individuals within populations in order to test LD differences for each pair of loci. Using this approach we propose a solution to the problem of testing multiple locus-pairs by means of a single test for the number of pairs that exhibit significant LD differences among populations. The second method provides the Bayesian posterior probability that one population has greater LD than the other for each locus pair. Both methods can handle genotypes with unknown phase, and are demonstrated using two data sets. For the purpose of demonstration, we apply the methods to two different sets of data from humans. First, we explore the issue of LD differences between reproductively isolated populations using a new data set of twelve Xq25 microsatellites, typed in four European populations. Second, we examine evidence for LD differences between Alzheimer cases and controls from the Icelandic population using 19 single nucleotide polymorphisms (SNPs) from a 97 kb region flanking the Apolipoprotein E (APOE) gene on chromosome 19. [source] Value of anti,modified citrullinated vimentin and third-generation anti,cyclic citrullinated peptide compared with second-generation anti,cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2009Michael P. M. van der Linden Objective Autoantibodies such as rheumatoid factor (RF) and anti,citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti,cyclic citrullinated peptide (anti,CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti,CCP-3) and anti,modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD),free remission in RA. Methods Patients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti,CCP-2, anti,CCP-3, anti-MCV, and RF) and between combinations of these tests. Results Among the single tests performed in patients with UA, anti,CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. Conclusion For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA. [source] ESTIMATING THE FALSE NEGATIVE FRACTION FOR A MULTIPLE SCREENING TEST FOR BOWEL CANCER WHEN NEGATIVES ARE NOT VERIFIEDAUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 4 2004Chris J. Lloyd Summary This paper aims to estimate the false negative fraction of a multiple screening test for bowel cancer, where those who give negative results for six consecutive tests do not have their true disease status verified. A subset of these same individuals is given a further screening test, for the sole purpose of evaluating the accuracy of the primary test. This paper proposes a beta heterogeneity model for the probability of a diseased individual ,testing positive' on any single test, and it examines the consequences of this model for inference on the false negative fraction. The method can be generalized to the case where selection for further testing is informative, though this did not appear to be the case for the bowel-cancer data. [source] Do tests of malingering concur?BEHAVIORAL SCIENCES & THE LAW, Issue 5 2006Concordance among malingering measures Malingering test accuracy is increasingly a major issue in psychology and law. Integrating results across measures might offset limitations of a single test, but the practical benefits of using several tests depend on the extent to which they misclassify the same individuals. Data from 66 evaluatees were used to assess the degree of overlap and consistency of classification among several commonly used malingering instruments. Although correlative data indicated that measures were highly redundant even across symptom domains, classification accuracy analyses revealed that findings based on conjunctions of these scales may not overlap to the degree that the correlations might suggest. Copyright © 2006 John Wiley & Sons, Ltd. [source] A Comparison of Eight Methods for the Dual-Endpoint Evaluation of Efficacy in a Proof-of-Concept HIV Vaccine TrialBIOMETRICS, Issue 3 2006Devan V. Mehrotra Summary To support the design of the world's first proof-of-concept (POC) efficacy trial of a cell-mediated immunity-based HIV vaccine, we evaluate eight methods for testing the composite null hypothesis of no-vaccine effect on either the incidence of HIV infection or the viral load set point among those infected, relative to placebo. The first two methods use a single test applied to the actual values or ranks of a burden-of-illness (BOI) outcome that combines the infection and viral load endpoints. The other six methods combine separate tests for the two endpoints using unweighted or weighted versions of the two-part z, Simes', and Fisher's methods. Based on extensive simulations that were used to design the landmark POC trial, the BOI methods are shown to have generally low power for rejecting the composite null hypothesis (and hence advancing the vaccine to a subsequent large-scale efficacy trial). The unweighted Simes' and Fisher's combination methods perform best overall. Importantly, this conclusion holds even after the test for the viral load component is adjusted for bias that can be introduced by conditioning on a postrandomization event (HIV infection). The adjustment is derived using a selection bias model based on the principal stratification framework of causal inference. [source] Strategies for improving the diagnostic specificity of the frequency doubling perimeterACTA OPHTHALMOLOGICA, Issue 1 2005Govert P. Heeg Abstract. Purpose:,To evaluate various strategies designed to improve the specificity of the interpretation of results obtained with the frequency doubling technology perimeter (FDT) used in the full-threshold mode. Methods:,Three different strategies were compared using data from 452 glaucoma patients and 237 healthy subjects: combining several FDT parameters from a single test, combining the FDT test with a GDx test, and confirming an abnormal FDT test result with a repeat test. Results:,Confirming an abnormal FDT test result with a repeat test yielded a specificity increase of 0.10, from 0.80 to 0.90, at the expense of some loss of sensitivity for early but not for moderate or severe glaucoma. Combining several FDT parameters from a single test and combining FDT with GDx did not yield any noticeable increase in diagnostic performance. Conclusions:,A modest increase in FDT diagnostic performance can be obtained by the confirmation of an abnormal test result with a repeat test. [source] Targeted screening for undiagnosed diabetes reduces the number of diagnostic tests.DIABETIC MEDICINE, Issue 8 2004Inter99(8) Abstract Aims To determine the cost and performance of a Danish risk score, fasting plasma glucose (FPG), and HbA1c as single screening tests and in combination with targeted screening. Subjects and methods In the Inter99 study, 12 934 inhabitants of Copenhagen County were invited to participate. All participants underwent anthropometric measurements, blood samples, and a 75-g standardized oral glucose tolerance test [N = 6784 (52.5%)]. Results Of the 6117 individuals included in the analysis, 252 (4.1%) had previously undiagnosed diabetes. As a stand-alone test, the FPG had the highest performance expressed by a significantly higher area under the receiver,operating curve [0.89; 95% confidence interval (CI) 0.86, 0.99] compared with the Danish risk score (0.78; 95% CI 0.76, 0.81) and HbA1c (0.76; 95% CI 0.72, 0.80). Targeted screening where the initial test was a risk score reduced the FPG measurements by 72% (100% vs. 27.8%). Using FPG in population-based screening, the cost per newly diagnosed diabetic individual was 583 euro compared with 270 euro if screened by questionnaire followed by FPG. The sensitivity and specificity were 78.6% and 87.7% for FPG, and 61.5% and 89.2% for the combination of the questionnaire and FPG, respectively. Conclusions The performance of FPG was superior to a questionnaire and HbA1c used as single tests. However taking into account workload, the burden on the population and the cost per identified person with undiagnosed diabetes, targeted screening using a questionnaire followed by FPG appears to be the strategy of choice. Diabet. Med. (2004) [source] Value of anti,modified citrullinated vimentin and third-generation anti,cyclic citrullinated peptide compared with second-generation anti,cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2009Michael P. M. van der Linden Objective Autoantibodies such as rheumatoid factor (RF) and anti,citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti,cyclic citrullinated peptide (anti,CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti,CCP-3) and anti,modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD),free remission in RA. Methods Patients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti,CCP-2, anti,CCP-3, anti-MCV, and RF) and between combinations of these tests. Results Among the single tests performed in patients with UA, anti,CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. Conclusion For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA. [source] |