scholarly journals Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay

2019 ◽  
Vol 4 (1) ◽  
pp. 30-39 ◽  
Author(s):  
Adrienne Tin ◽  
Bing Yu ◽  
Jianzhong Ma ◽  
Kunihiro Masushita ◽  
Natalie Daya ◽  
...  

Abstract Background There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. Methods We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4–9 weeks) and long-term (approximately 20 years) variability using paired t-tests with log-transformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). Results The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs < 5.0%, Spearman correlations > 0.89, and ICCs > 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P < 1.4 × 10−5, 681 increased, 185 decreased). PC1 had high correlations with age (−0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31). Conclusions Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan.

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Janice E Williams ◽  
Sharon B Wyatt ◽  
Kathryn M Rose ◽  
David J Couper ◽  
Anna Kucharska-Newton

Though several large epidemiologic studies have demonstrated the positive association of anger with coronary heart disease (CHD) onset, a dearth of population-based evidence exists regarding the relationship of anger to the clinical course of CHD among people with established disease. Trait anger is conceptualized as a stable personality trait and defined as the tendency to experience frequent and intense anger. Therefore, it is plausible that the effects of trait anger on CHD are long standing. We assessed the hypothesis that trait anger predicts short-term and long-term risk for recurrent CHD among middle-aged men and women. Participants were 611 black or white men and women, ages 48 - 67, who had a history of CHD at the second clinical examination (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. They were followed for the recurrence of CHD (myocardial infarction or fatal CHD) from 1990 through three different time intervals: 1995, 2003, and 2009 (maximum follow-up = 19.0 years). Trait anger (measured at Visit 2) was assessed using the Spielberger Trait Anger Scale, with scores categorized as high, moderate, and low. Cox proportional hazards regression analyses were adjusted for age, sex, race-center, educational level, waist-to-hip ratio, plasma LDL-and HDL-cholesterol levels, hypertension, diabetes, cigarette smoking status, and pack-years of cigarette smoking. After 3 - 5 years of follow-up, the risk for recurrent CHD among participants with high trait anger was more than twice that of their counterparts with low trait anger (2.24 [95% C.I: 1.14 to 4.40]). After 11 - 13 years, the risk was 80% greater (1.80 [95% C.I: 1.17 to 2.78]) and after 17 - 19 years, it was 70% greater (1.70 [95% C.I: 1.15 to 2.52]). The risk for recurrent CHD was strongest in the first time interval but remained strong and statistically significant through 19 years of follow-up. In conclusion, the experience of frequent and intense anger increases short-term and long-term risk for recurrent CHD in middle-aged men and women.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245459
Author(s):  
Qinying Huang ◽  
Jinying Li

Background Although previously published meta-analyses have compared the surgical effects between the methods of Idiopathic epiretinal membrane (iERM) removal with or without ILM peeling, they did not reach an agreement. Purpose We aimed to provide more evidence for the treatment of iERM and whether additional ILM peeling was better or not by analyzing more updated studies and randomized control trials (RCTs). Method The search was conducted in Pubmed, Embase, Cochrane Library, Web of Science and Open Grey without language limitation and the studies included were from inception to December 2019. All studies of iERM with or without ILM peeling showed at least one of outcomes, such as best-corrected visual acuity (BCVA), central macular thickness (CMT) and recurrence of ERM. The pooled results between above groups were showed by the mean differences (MDs) and risk ratios (RR) with corresponding 95% confidence intervals (CIs). Result In total, 1645 eyes of five randomized controlled trials (RCTs) and fifteen retrospective studies were included. The short-term (<12 months) BCVA improvement in both groups showed no significant difference (MD = -0.01; 95% CI = -0.02 to 0.01; P = 0.36). However, the BCVA improvement was significantly better in ILM peeling eyes than in those without ILM peeling when considering the risk bias (MD = -0.04; 95% CI = -0.07 to -0.01; P = 0.008). The short-term (<12 months) CMT had a higher reduction in non ILM peeling group (MD = -9.02; 95% CI = -12.51 to -5.54; P < 0.00001) and the recurrence of ERM in ILM peeling group was lower (P < 0.00001). The long-term (≥12months) BCVA improvement ((MD = -0.00; 95% CI = -0.03 to 0.03; P = 0.97) and reduction of long-term (≥12months) CMT (MD = -1.14; 95% CI = -7.14 to -4.86; P = 0.71) were similar in both groups. Conclusion By considering the risk of bias, we should determine whether ILM peeling is beneficial for short-term changes in BCVA in patients with iERM. Nevertheless, further studies are needed to confirm this. iERM removal without ILM peeling can improve the short-term decrease in CMT and ILM peeling decreases the recurrence of ERM, but the long-term changes in BCVA and CMT are similar with or without ILM peeling. There is a need for a true large scale randomized trial that will also include microperimetry and other functional measures.


Electronics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 534
Author(s):  
Huogen Wang

The paper proposes an effective continuous gesture recognition method, which includes two modules: segmentation and recognition. In the segmentation module, the video frames are divided into gesture frames and transitional frames by using the information of hand motion and appearance, and continuous gesture sequences are segmented into isolated sequences. In the recognition module, our method exploits the spatiotemporal information embedded in RGB and depth sequences. For the RGB modality, our method adopts Convolutional Long Short-Term Memory Networks to learn long-term spatiotemporal features from short-term spatiotemporal features obtained from a 3D convolutional neural network. For the depth modality, our method converts a sequence into Dynamic Images and Motion Dynamic Images through weighted rank pooling and feed them into Convolutional Neural Networks, respectively. Our method has been evaluated on both ChaLearn LAP Large-scale Continuous Gesture Dataset and Montalbano Gesture Dataset and achieved state-of-the-art performance.


2019 ◽  
Vol 17 (12) ◽  
pp. 1497-1504
Author(s):  
Lucas K. Vitzthum ◽  
Chris Straka ◽  
Reith R. Sarkar ◽  
Rana McKay ◽  
J. Michael Randall ◽  
...  

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer–specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. Results: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85–1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93–1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57–0.95) and OS (SHR, 0.82; 95% CI, 0.73–0.93). Conclusions: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wendy Wang ◽  
Riccardo M Inciardi ◽  
Faye L Norby ◽  
Michael J Zhang ◽  
Jorge L Reyes ◽  
...  

Introduction: Black Americans have more atrial fibrillation (AF) risk factors but lower AF risk than whites. Left atrial (LA) enlargement, impaired LA function, frequent premature atrial contractions (PAC), and atrial tachycardia (AT) are risk factors for AF. Racial differences in LA size and function, PAC, or AT may exist that could explain the difference in AF risk. Hypothesis: Whites have higher PAC and AT frequency than blacks. Additionally, whites have larger LA size and lower LA function than blacks, which may contribute to the racial difference in AF. Methods: We included 1,623 ARIC participants free of AF who had 2D-echocardiograms at visit 5 (2011-2013) and wore a 2-week continuous heart monitor, the Zio ® XT Patch, at visit 6 (2016-2017). Weighted linear regression was used to analyze the association of race with LA size and function, as well as runs of AT per day and PAC per hour. Results: At visit 5, participants were 74 (4) years old, 58% were female, and 26% were black. AT runs were detected in 87% of blacks and 92% of whites, respectively (p=0.002). Among participants with >0 runs of AT per day (n=1480), blacks had 48% (95% CI: 21%-66%) fewer runs of AT per day than whites after adjustment for cardiovascular (CV) risk factors † . There was no significant difference in PAC frequency between blacks and whites. After adjusting for age and sex, blacks had greater LA size and lower LA function than whites; these differences attenuated after adjusting for CV risk factors (Table). Conclusion: Blacks have greater age and sex-adjusted abnormality in LA size and function than whites, likely due to higher prevalence of CV risk factors. Yet, blacks have lower propensity for AT. More research is needed to elucidate the mechanisms underlying the resistance to atrial arrhythmogenesis in blacks despite greater adverse LA remodeling.


2016 ◽  
Vol 13 (24) ◽  
pp. 6651-6667 ◽  
Author(s):  
Jing Tang ◽  
Guy Schurgers ◽  
Hanna Valolahti ◽  
Patrick Faubert ◽  
Päivi Tiiva ◽  
...  

Abstract. The Arctic is warming at twice the global average speed, and the warming-induced increases in biogenic volatile organic compounds (BVOCs) emissions from Arctic plants are expected to be drastic. The current global models' estimations of minimal BVOC emissions from the Arctic are based on very few observations and have been challenged increasingly by field data. This study applied a dynamic ecosystem model, LPJ-GUESS, as a platform to investigate short-term and long-term BVOC emission responses to Arctic climate warming. Field observations in a subarctic tundra heath with long-term (13-year) warming treatments were extensively used for parameterizing and evaluating BVOC-related processes (photosynthesis, emission responses to temperature and vegetation composition). We propose an adjusted temperature (T) response curve for Arctic plants with much stronger T sensitivity than the commonly used algorithms for large-scale modelling. The simulated emission responses to 2 °C warming between the adjusted and original T response curves were evaluated against the observed warming responses (WRs) at short-term scales. Moreover, the model responses to warming by 4 and 8 °C were also investigated as a sensitivity test. The model showed reasonable agreement to the observed vegetation CO2 fluxes in the main growing season as well as day-to-day variability of isoprene and monoterpene emissions. The observed relatively high WRs were better captured by the adjusted T response curve than by the common one. During 1999–2012, the modelled annual mean isoprene and monoterpene emissions were 20 and 8 mg C m−2 yr−1, with an increase by 55 and 57 % for 2 °C summertime warming, respectively. Warming by 4 and 8 °C for the same period further elevated isoprene emission for all years, but the impacts on monoterpene emissions levelled off during the last few years. At hour-day scale, the WRs seem to be strongly impacted by canopy air T, while at the day–year scale, the WRs are a combined effect of plant functional type (PFT) dynamics and instantaneous BVOC responses to warming. The identified challenges in estimating Arctic BVOC emissions are (1) correct leaf T estimation, (2) PFT parameterization accounting for plant emission features as well as physiological responses to warming, and (3) representation of long-term vegetation changes in the past and the future.


Author(s):  
Nick Perham ◽  
Toni Howell ◽  
Andy Watt

AbstractFunding to support students with dyslexia in post-compulsory education is under pressure and more efficient assessments may offset some of this shortfall. We tested potential tasks for screening dyslexia: recall of adjective-noun, compared to noun-adjective, pairings (syntax) and recall of high versus low frequency letter pairings (bigrams). Students who reported themselves as dyslexic failed to show a normal syntax effect (greater recall of adjective-noun compared to noun-adjective pairings) and no significant difference in recall between the two types of bigrams whereas students who were not dyslexic showed the syntax effect and a bias towards recalling high frequency bigrams. Findings are consistent with recent explanations of dyslexia suggesting that those affected find it difficult to learn and utilise sequential long-term order information (Szmalec et al. Journal of Experimental Psychology: Learning, Memory & Cognition, 37(5) ,1270-1279, 2011). Further, ROC curve analyses revealed both tasks showed acceptable diagnostic properties as they were able to discriminate between the two groups of participants.


2020 ◽  
Vol 11 (4) ◽  
pp. 192-197
Author(s):  
Gavin Goldsbrough ◽  
Helen Reynolds

Background: Meloxicam is an analgesic agent with anti-inflammatory properties, commonly used in veterinary practices to treat a variety of different long-term medical conditions and is also used as a short-term pain relief following particularly traumatic surgeries. Aims: An observational study was conducted to determine whether meloxicam provides adequate pain management as a post-operative analgesic for canine ovariohysterectomies. Methods: 13 canines were admitted for ovariohysterectomy. Each patient was assessed using the Glasgow composite pain scale (CMPS) prior to surgery during the admission procedure, 15 minutes post-operatively, at discharge and at their post-operative check (POC) 3–5 days after surgery. Results: Data were statistically analysed to determine the overall effectiveness of meloxicam in reducing pain following canine ovariohysterectomy. The results showed a statistically significant difference (Kruskal-Wallis test: H3 =12.98, p=0.005) in pain scores between admission, 15 minutes post operatively, discharge and 3–5 days POC. The greatest decrease in pain score was between 15 minutes post-operatively and POC (Mann-Whitney U test: W=236, n=13, 13, p=0.0014) and between discharge and POC (Mann-Whitney U test: W=227, n=13, 13, p=0.0060). Overall, this demonstrated that there was an improvement in pain suggesting meloxicam is effective between these time frames. In addition, 69.2% (n=9) of patients in the study showed a pain score of 0, indicating an absence of pain, on their final POC. Statistical analysis was also used to determine if there was any difference in pain score between the 3, 4 or 5 day POC pain score. The results show there was no significant difference (Kruskal-Wallis test: H2 =0.090, p=0.638) suggesting that meloxicam's effectiveness was similar across this range of time post surgery. Conclusion: The results from the study indicate that meloxicam is an effective post-operative analgesic for canine patients undergoing an ovariohysterectomy.


2020 ◽  
Vol 133 (5) ◽  
pp. 1450-1459
Author(s):  
Yu Chen ◽  
Li Ma ◽  
Junlin Lu ◽  
Xiaolin Chen ◽  
Xun Ye ◽  
...  

OBJECTIVEPostoperative hemorrhage during the acute phase is rarely observed after revascularization surgery for moyamoya disease (MMD) but can have severe complications. Its risk factors and outcomes are still unclear. The aim of this study was to investigate the predictors of postoperative hemorrhage during the acute phase in MMD and examine the outcomes of the hemorrhage.METHODSThe authors reviewed the preoperative clinical characteristics and radiographic features of 465 consecutive MMD cases (518 procedures) that had undergone direct or combined bypass surgery at their institution between 2009 and 2015. Patients with postoperative intracerebral hemorrhage (ICH) or ICH plus intraventricular hemorrhage (IVH) during the acute phase were screened, and then the incidence, location, and risk factors of hemorrhage in these patients were analyzed. Short-term and long-term outcomes (modified Rankin Scale scores) for these patients were also collected. Outcomes were compared between patients with and those without postoperative ICH using propensity score analysis to reduce the between-group differences in baseline characteristics.RESULTSPostoperative hemorrhage occurred in 11 (2.1%; ICH = 9, IVH = 2) of 518 procedures (mean patient age 39.82 ± 8.8 years). Hemorrhage occurred in the first 24 hours after the operation in 8 cases (72.7%). In the ICH group, most of the hemorrhage sites (77.8%) were located beneath the anastomosed area, and the mean hematoma volume was 16.98 ± 22.45 ml (range 3–57 ml). One case from the ICH group required hematoma evacuation. Among the adult patients (463 procedures [89.4%]), preoperative hypertension (p = 0.008), CT perfusion (CTP) stage > III (p = 0.013), and posterior circulation involvement (p = 0.022) were significantly associated with postoperative ICH. No significant differences between the postoperative ICH group and the no-hemorrhage group were detected in terms of postoperative neurofunctional status at discharge (p = 0.569) or at the last follow-up (p = 1.000). Neither was there a significant difference in future stroke risk (p = 0.538) between these two groups.CONCLUSIONSPreoperative hypertension, CTP stage > III, and posterior circulation involvement are independent risk factors for postoperative ICH after direct or combined revascularization for MMD. After appropriate perioperative management, postoperative ICH has no significant correlations with the postoperative short-term and long-term neurofunctional status.


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