Serum autoantibody measurement for the detection of hepatocellular carcinoma

Background: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC.Methods: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA.Results: Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel.Conclusions: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung)

Paraoxonase 1 (PON1) Polymorphisms, Haplotypes and Activity in Predicting CAD Risk in North-West Indian Punjabis

Human serum paraoxonase-1 (PON1) prevents oxidation of low density lipoprotein cholesterol (LDL-C) and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD) risk. As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.350 angiographically proven (≥ 70% stenosis) CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase) and phenylacetate (Arylesterase; AREase) substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide -PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57-4.72)) and RR (OR, 16.24 (6.41-41.14)) genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02-4.21)) genotype of -162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72-6.16)) and L-T-G-R-G (OR: 2.82 (1.01-7.80)) were also significantly associated with CAD.In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter -162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

An open-standard file format for forensic audio

In this paper we discuss a proposal for an open standard for a forensic audio file format, to be used in the acquisition, processing, and archival of audio data as forensic evidence. This is an open file format deriving from and extending existing wave file formats, while remaining fully compatible with them. This standard can be used by audio specialists as well as vendors of audio recording hardware to include additional information that is useful for forensic and law enforcement purposes. In conducting forensic audio analysis, the forensic expert has to take care to ensure the integrity of the audio data under consideration as evidence, and maintain records pertaining to the analysis. With modern audio-editing software it has become increasingly easy, inadvertently or otherwise, to alter an audio recording in ways that may make it unacceptable in the courts as evidence. In addition, searching for and retrieving specific desired audio recordings is becoming increasingly difficult as storage of digital audio evidence becomes more prevalent. There is a need, therefore, for standardization of an audio format that takes into consideration the requirements of forensic analysis, search and retrieval. These requirements include, among other things, checks to ensure that the integrity of the original sample is maintained, that the details of the case and the specialist examining the sample are logged at every stage, and that the audio data is appropriately tagged. This ope

Bilateral Comparison And Reliability Of Ground Reaction Forces During Single Leg Hop Test

PURPOSE: To compare single leg horizontal hop ground reaction forces (GRF) between the dominant (DOM) and non-dominant (NDOM) limbs and to determine the reliability GRF based variables. METHODS: After a standardized warm-up, 20 (10 men, 10 women) physically active (Tegner score = 6.5 +/- 1.7, range 4-9) young adults (21.7 +/- 2.1 yrs) performed three DOM and three NDOM single leg horizontal hops in random order during two sessions 72 hours apart. In addition to recording hop distance, GRF were used to calculate 10 variables using the vertical (vGRF) and anterior-posterior (apGRF) GRF: peak, peak to ground off (GO), impulse, average force, and impulse time. Reliability was assessed across session one trials (intrasession) and between sessions one and two (intersession) using intraclass correlation coefficients (ICC) and standard error of measurement. Separate two factor analysis of variance were conducted to assess interactions between limb (DOM, NDOM) and direction (vGRF, apGRF) using the session one three trial average. The relationship between hop distance and GRF variables were established using correlational analyses. RESULTS: No significant hop distance difference was found (t19 = -.840, P =.412) between the NDOM (1.07 ±.12 % ht, 95% CI: 1.03 - 1.09)(and DOM (1.06 ±.11 % ht, 95% 1.02 - 1.08) limbs. Similarly there were no significant limb differences (interactions or main effects) for any of the GRF variables (P\u3e.05). A significant direction main effect was observed for peak (vGRF\u3eaGRF, PaGRF, P\u3c.001), average force (vGRF\u3eaGRF, PvGRF, P.75) with the exception of intrasession vGRF peak to GO (both limbs). Four GRF variables significantly related to hop distance: DOM vGRF impulse (r =.480, P =.032), DOM aGRF peak (r =.524, P =.018), DOM aGRF impulse (r =.677, P =.001) and NDOM aGRF impulse (r =.765, P\u3c.001). CONCLUSION: Equal hop distances and underlying GRF may be expected between DOM and NDOM in healthy individuals. Except vGRF peak to GO, all GRF based variables were reliable. Further research is needed to determine if GRF analyses increases the sensitivity of the single leg hop test in identifying performance deficits, and/or injury predisposition

Bilateral Comparison and Reliability of Ground Reaction Forces During Single Leg Hop Test

Presentation given at the Annual Meeting of the American College of Sports Medicine

Bilateral Comparison of Propulsion Mechanics During Single-Leg Vertical Jumping

McElveen, MT, Riemann BL, and Davies GJ. Bilateral comparison of propulsion mechanics during single-leg vertical jumping. J Strength Cond Res 24(2): 375-381, 2010. The primary purpose of this investigation was to compare single leg vertical jump performance and several performance characteristics derived from vertical ground reaction forces (vGRF) between the dominant (DOM) and nondominant (NDOM) legs. Secondary purposes included determining the relationship between the kinetic and temporal characteristics and single leg vertical jump performance and establishing the intrasession and intersession reliability of the characteristics considered. After a standardized warm-up, 20 physically active young adults (10 men, 10 women) performed three single leg DOM and three single leg NDOM vertical jumps in a random order during two sessions separated by three days. vGRF collected during each trial were used to calculate jump height, peak vertical power, peak vGRF, vGRF impulse, ratio between negative to positive vGRF impulse, time between maximum peak power to takeoff and countermovement depth. There were no significant differences between DOM and NDOM for jump height (p = .145) as well as the six characteristics considered (p \u3e .05). There was a strong, direct relationship between jump height and peak vertical power for both DOM (r = .915, p \u3c .001) and NDOM (r = .944, p \u3c .001). With the exception of vGRF negative/positive impulse ratio, all dependent variables demonstrated moderate to high intrasession and intersession reliability. These results support using a single leg vertical jump protocol for conducting bilateral lower extremity functional assessments. With the exception of impulse ratio, the reliability results support using the protocol for serial assessments. In conclusion, healthy individuals can be expected to exhibit near equal single leg vertical jumping performance bilaterally, providing practitioners with a basis to interpret performance

Bilateral Comparison of Propulsion Mechanics During Single Leg Vertical Jumping

Presentation given at the Annual Meeting of the American College of Sports Medicine