Publications by authors named "Yijian Huang"

78 Publications

A varying-coefficient model for gap times between recurrent events.

Lifetime Data Anal 2021 Jul 8;27(3):437-459. Epub 2021 May 8.

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.

Recurrent events often arise in follow-up studies where a subject may experience multiple occurrences of the same type of event. Most regression models for recurrent events consider the time scale measured from the study origin and assume constant effects of covariates. In many applications, however, gap times between recurrent events are of natural interest and moreover the effects may actually vary over time. In this article, we propose a marginal varying-coefficient model for gap times between recurrent events that allows for the intra-individual correlation between events. Estimation and inference procedures are developed for the varying coefficients. Consistency and weak convergence of the proposed estimator are established. Monte Carlo simulation studies demonstrate that the proposed method works well with practical sample sizes. The proposed method is illustrated with an analysis of bladder tumor clinical data.
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http://dx.doi.org/10.1007/s10985-021-09523-7DOI Listing
July 2021

Genomics of response to porcine reproductive and respiratory syndrome virus in purebred and crossbred sows: antibody response and performance following natural infection vs. vaccination.

J Anim Sci 2021 May;99(5)

Department of Animal Science, Iowa State University, Ames, IA 50011, USA.

Antibody response, measured as sample-to-positive (S/P) ratio, to porcine reproductive and respiratory syndrome virus (PRRSV) following a PRRSV-outbreak (S/POutbreak) in a purebred nucleus and following a PRRSV-vaccination (S/PVx) in commercial crossbred herds have been proposed as genetic indicator traits for improved reproductive performance in PRRSV-infected purebred and PRRSV-vaccinated crossbred sows, respectively. In this study, we investigated the genetic relationships of S/POutbreak and S/PVx with performance at the commercial (vaccinated crossbred sows) and nucleus level (non-infected and PRRSV-infected purebred sows), respectively, and tested the effect of previously identified SNP for these indicator traits. Antibody response was measured on 541 Landrace sows ~54 d after the start of a PRRSV outbreak, and on 906 F1 (Landrace × Large White) gilts ~50 d after vaccination with a commercial PRRSV vaccine. Reproductive performance was recorded for 711 and 428 Landrace sows before and during the PRRSV outbreak, respectively, and for 811 vaccinated F1 animals. The estimate of the genetic correlation (rg) of S/POutbreak with S/PVx was 0.72 ± 0.18. The estimates of rg of S/POutbreak with reproductive performance in vaccinated crossbred sows were low to moderate, ranging from 0.05 ± 0.23 to 0.30 ± 0.20. The estimate of rg of S/PVx with reproductive performance in non-infected purebred sows was moderate and favorable with number born alive (0.50 ± 0.23) but low (0 ± 0.23 to -0.11 ± 0.23) with piglet mortality traits. The estimates of rg of S/PVx were moderate and negative (-0.38 ± 0.21) with number of mummies in PRRSV-infected purebred sows and low with other traits (-0.30 ± 0.18 to 0.05 ± 0.18). Several significant associations (P0 > 0.90) of previously reported SNP for S/P ratio (ASGA0032063 and H3GA0020505) were identified for S/P ratio and performance in non-infected purebred and PRRSV-exposed purebred and crossbred sows. Genomic regions harboring the major histocompatibility complex class II region significantly contributed to the genetic correlation of antibody response to PRRSV with most of the traits analyzed. These results indicate that selection for antibody response in purebred sows following a PRRSV outbreak in the nucleus and for antibody response to PRRSV vaccination measured in commercial crossbred sows are expected to increase litter size in purebred and commercial sows.
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http://dx.doi.org/10.1093/jas/skab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118356PMC
May 2021

Evidence for recombination variability in purebred swine populations.

J Anim Breed Genet 2021 Mar 25;138(2):259-273. Epub 2020 Sep 25.

Department of Animal Science, North Carolina State University, Raleigh, NC, USA.

This study aimed to investigate interpopulation variation due to sex, breed and age, and the intrapopulation variation in the form of genetic variance for recombination in swine. Genome-wide recombination rate and recombination occurrences (RO) were traits studied in Landrace (LR) and Large White (LW) male and female populations. Differences were found for sex, breed, sex-breed interaction, and age effects for genome-wide recombination rate and RO at one or more chromosomes. Dams were found to have a higher genome-wide recombination rate and RO at all chromosomes than sires. LW animals had higher genome-wide recombination rate and RO at seven chromosomes but lower at two chromosomes than LR individuals. The sex-breed interaction effect did not show any pattern not already observable by sex. Recombination increased with increasing parity in females, while in males no effect of age was observed. We estimated heritabilities and repeatabilities for both investigated traits and obtained the genetic correlation between male and female genome-wide recombination rate within each of the two breeds studied. Estimates of heritability and repeatability were low (h  = 0.01-0.26; r = 0.18-0.42) for both traits in all populations. Genetic correlations were high and positive, with estimates of 0.98 and 0.94 for the LR and LW breeds, respectively. We performed a GWAS for genome-wide recombination rate independently in the four sex/breed populations. The results of the GWAS were inconsistent across the four populations with different significant genomic regions identified. The results of this study provide evidence of variability for recombination in purebred swine populations.
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http://dx.doi.org/10.1111/jbg.12510DOI Listing
March 2021

[F]Fluciclovine Positron Emission Tomography/Computerized Tomography for Preoperative Staging in Patients with Intermediate to High Risk Primary Prostate Cancer.

J Urol 2020 10 29;204(4):734-740. Epub 2020 Apr 29.

Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia.

Purpose: Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [F]fluciclovine positron emission tomography/computerized tomography is an early indicator of subclinical metastasis among patients with high risk prostate cancer.

Materials And Methods: A total of 68 patients with unfavorable intermediate to very high risk prostate cancer without systemic disease on conventional imaging were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection. Diagnostic performance of [F]fluciclovine positron emission tomography/computerized tomography and conventional imaging for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined.

Results: Overall 57 of 68 patients completed the protocol, of whom 31 had nodal metastasis on histology. [F]Fluciclovine positron emission tomography/computerized tomography sensitivity and specificity in detecting nodal metastasis was 55.3% and 84.8% per patient, and 54.8% and 96.4% per region (right and left pelvis, presacral and nonregional), respectively. Compared with conventional imaging [F]Fluciclovine positron emission tomography/computerized tomography had significantly higher sensitivity on patient based (55.3% vs 33.3%, p <0.01) and region based (54.8% vs 19.4%, p <0.01) analysis, detecting metastasis in 7 more patients and 22 more regions, with similar high specificity. Four additional patients had distant disease or other cancer detected on [F] fluciclovine positron emission tomography/computerized tomography which precluded surgery. Detection of metastasis was related to size of metastatic deposits within lymph nodes and overall metastatic burden.

Conclusions: [F]Fluciclovine positron emission tomography/computerized tomography detects occult metastases not identified on conventional imaging and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.
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http://dx.doi.org/10.1097/JU.0000000000001095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059474PMC
October 2020

Helicity Enhanced Torsion Sensor Based on Liquid Filled Twisted Photonic Crystal Fibers.

Sensors (Basel) 2020 Mar 9;20(5). Epub 2020 Mar 9.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

A highly sensitive torsion sensor can be constructed by combining a twisted photonic crystal fiber with a liquid-filled waveguide in its air-hole cladding. The torsion sensitivity of this type of sensor is determined directly by the phase-matching conditions between the fiber core mode and the liquid waveguide mode, which can be improved by tuning the helicity (denoted by the initial twist rate, ) of the twisted photonic crystal fiber. The enhancement mechanism of on the sensitivity of the proposed torsion sensor is investigated theoretically, followed by experimental verifications, and a torsion sensitivity as high as 446 nm∙mm∙rad can be obtained by tailoring these parameters. Experimental results show that the torsion sensitivity increases with decreasing from 3.142 to 3.925 rad/mm, which are in consistence with that of the numerical predictions. The demonstrated torsion sensor is expected to contribute to the development of highly sensitive torsion-related photonic crystal fiber devices.
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http://dx.doi.org/10.3390/s20051490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085693PMC
March 2020

Comparison of Rates of Central Line-Associated Bloodstream Infections in Patients With 1 vs 2 Central Venous Catheters.

JAMA Netw Open 2020 03 2;3(3):e200396. Epub 2020 Mar 2.

School of Medicine, Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia.

Importance: National Healthcare Safety Network methods for central line-associated bloodstream infection (CLABSI) surveillance do not account for potential additive risk for CLABSI associated with use of 2 central venous catheters (CVCs) at the same time (concurrent CVCs); facilities that serve patients requiring high acuity care with medically indicated concurrent CVC use likely disproportionally incur Centers for Medicare & Medicaid Services payment penalties for higher CLABSI rates.

Objective: To quantify the risk for CLABSI associated with concurrent use of a second CVC.

Design, Setting, And Participants: This retrospective cohort study included adult patients with 2 or more days with a CVC at 4 geographically separated general acute care hospitals in the Atlanta, Georgia, area that varied in size from 110 to 580 beds, from January 1, 2012, to December 31, 2017. Variables included clinical conditions, central line-days, and concurrent CVC use. Patients were propensity score-matched for likelihood of concurrence (limited to 2 CVCs), and conditional logistic regression modeling was performed to estimate the risk of CLABSI associated with concurrence. Episodes of CVC were categorized as low or high risk and single vs concurrent use to evaluate time to CLABSI with Cox proportional hazards regression models. Data were analyzed from January to June 2019.

Exposures: Two CVCs present at the same time.

Main Outcomes And Measures: Hospitalizations in which a patient developed a CLABSI, allowing estimation of patient risk for CLABSI and daily hazard for a CVC episode ending in CLABSI.

Results: Among a total of 50 254 patients (median [interquartile range] age, 59 [45-69] years; 26 661 [53.1%] women), 64 575 CVCs were used and 647 CLABSIs were recorded. Concurrent CVC use was recorded in 6877 patients (13.7%); the most frequent indications for concurrent CVC use were nutrition (554 patients [14.1%]) or hemodialysis (1706 patients [43.4%]). In the propensity score-matched cohort, 74 of 3932 patients with concurrent CVC use (1.9%) developed CLABSI, compared with 81 of 7864 patients with single CVC use (1.0%). Having 2 CVCs for longer than two-thirds of a patient's CVC use duration was associated with increased likelihood of developing a CLABSI, adjusting for central line-days and comorbidities (adjusted risk ratio, 1.62; 95% CI, 1.10-2.33; P = .001). In survival analysis adjusting for sex, receipt of chemotherapy or total parenteral nutrition, and facility, compared with a single CVC, the daily hazard for 2 low-risk CVCs was 1.78 (95% CI, 1.35-2.34; P < .001), while the daily hazard for 1 low-risk and 1 high-risk CVC was 1.80 (95% CI, 1.42-2.28; P < .001), and the daily hazard for 2 high-risk CVCs was 1.78 (95% CI, 1.14-2.77; P = .01).

Conclusions And Relevance: These findings suggest that concurrent CVC use is associated with nearly 2-fold the risk of CLABSI compared with use of a single low-risk CVC. Performance metrics for CLABSI should change to account for variations of this intrinsic patient risk among facilities to reduce biased comparisons and resultant penalties applied to facilities that are caring for more patients with medically indicated concurrent CVC use.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.0396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057131PMC
March 2020

Renshen Shouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 signaling pathway following ischemic stroke in rats.

J Ethnopharmacol 2020 May 31;253:112616. Epub 2020 Jan 31.

Guangdong Province Research Centre for Chinese Integrative Medicine Against Metabolic Disease, PR China; Guangdong TCM Key Laboratory Against Metabolic Diseases, PR China; Key Unit of Modulating Liver to Treat Hyperlipemia State Administration of Traditional Chinese Medicine, PR China; Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou, 510006, PR China. Electronic address:

Ethnopharmacological Relevance: Renshen Shouwu extract (RSSW) is a patented Traditional Chinese Medicine included in Chinese Pharmacopoeia for neurasthenia, forgetfulness, insomnia, inappetence and excessive fatigue. Our previous study had demonstrated the neuroprotective effect of RSSW against ischemic stroke in rats with middle cerebral artery occlusion (MCAO). However, its underlying mechanism remains unknown.

Aim Of The Study: In this study, we investigated the neurogenesis and angiogenesis effects of RSSW in ischemic stroke rats, and further revealed its underlying mechanism focused on TLR4/NF-κB/NLRP3 signaling pathway.

Materials And Methods: Firstly, active compounds of RSSW were determined by High Performance Liquid Chromatography (HPLC). Secondly, Middle cerebral artery occlusion (MCAO) was performed to induce ischemic stroke in rats and 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was employed to evaluate whether MCAO surgery was successfully established. Neurological deficit evaluation was conducted according to the Zea Longa' method. Then, we explored the neurogenesis and angiogenesis effects after oral administration of RSSW (50 mg/kg, 100 mg/kg) in MCAO-induced rats by Immunofluorescence Staining. Moreover, the proteins involved in TLR4/NF-κB/NLRP3 signaling pathway (TLR4, p-NF-κB p65, NF-κB p65, NLRP3, pro-IL-1β, IL-1β, pro-Caspase-1, Caspase-1) were determined by western blotting.

Results: It was observed that RSSW treatment significantly increased the number of newborn neurons and brain microvessel density (MVD) after ischemic stroke. What's more, RSSW treatment significantly downregulated TLR4, p-NF-κB p65/p65, NLRP3, pro-IL-1β, IL-1β, pro-Caspase-1, Caspase-1 proteins involved in TLR4/NF-κB/NLRP3 signaling pathway.

Conclusions: RSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.
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http://dx.doi.org/10.1016/j.jep.2020.112616DOI Listing
May 2020

Changes in genetic parameters for fitness and growth traits in pigs under genomic selection.

J Anim Sci 2020 Feb;98(2)

Department of Animal and Dairy Science, University of Georgia, Athens, GA.

Genomic selection increases accuracy and decreases generation interval, speeding up genetic changes in the populations. However, intensive changes caused by selection can reduce the genetic variation and can strengthen undesirable genetic correlations. The purpose of this study was to investigate changes in genetic parameters for fitness traits related with prolificacy (FT1) and litter survival (FT2 and FT3), and for growth (GT1 and GT2) traits in pigs over time. The data set contained 21,269 (FT1), 23,246 (FT2), 23,246 (FT3), 150,492 (GT1), and 150,493 (GT2) phenotypic records obtained from 2009 to 2018. The pedigree file included 369,776 animals born between 2001 and 2018, of which 39,103 were genotyped. Genetic parameters were estimated with bivariate models (FT1-GT1, FT1-GT2, FT2-GT1, FT2-GT2, FT3-GT1, and FT3-GT2) using 3-yr sliding subsets. With a Bayesian implementation using the GIBBS3F90 program computations were performed as genomic analysis (GEN) or pedigree-based analysis (PED), that is, with or without genotypes, respectively. For GEN (PED), the changes in heritability from the first to the last year interval, that is, from 2009-2011 to 2015-2018 were 8.6 to 5.6 (7.9 to 8.8) for FT1, 7.8 to 7.2 (7.7 to 10.8) for FT2, 11.4 to 7.6 (10.1 to 7.5) for FT3, 35.1 to 16.5 (32.5 to 23.7) for GT1, and 35.9 to 16.5 (32.6 to 24.1) for GT2. Differences were also observed for genetic correlations as they changed from -0.31 to -0.58 (-0.28 to -0.73) for FT1-GT1, -0.32 to -0.50 (-0.29 to -0.74) for FT1-GT2, -0.27 to -0.45 (-0.30 to -0.65) for FT2-GT1, -0.28 to -0.45 (-0.32 to -0.66) for FT2-GT2, 0.14 to 0.17 (0.11 to 0.04) for FT3-GT1, and 0.14 to 0.18 (0.11 to 0.05) for FT3-GT2. Strong selection in pigs reduced heritabilities and emphasized the antagonistic genetic relationships between fitness and growth traits. With genotypes considered, heritability estimates were smaller and genetic correlations were greater than estimates with only pedigree and phenotypes. When selection is based on genomic information, genetic parameters estimated without this information can be biased because preselection is not accounted for by the model.
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http://dx.doi.org/10.1093/jas/skaa032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039409PMC
February 2020

Self-Imaging Effect in Liquid-Filled Hollow-Core Capillary Waveguide for Sensing Applications.

Sensors (Basel) 2019 Dec 24;20(1). Epub 2019 Dec 24.

Guangdong and Hong Kong Joint Research Centre for Optical Fibre Sensors, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

A high sensitivity fiber-optic sensor based on self-imaging effect in a hollow-core capillary waveguide (HCCW) is presented for sensing applications. The sensor is composed of a section of HCCW fusion spliced between single mode fibers (SMFs). The self-imaging effect in the HCCW is investigated with different fiber lengths and arc-fusion parameters. By infiltrating the hollow core with index matching liquids, the peak wavelength of the proposed device shifts towards longer wavelengths. The temperature and refractive index (RI) responses of the sensor are studied systematically. When temperature is increased from 25 °C to 75 °C, the temperature sensitivity of the device can be improved significantly with the infiltrated structure, and reaches -0.49 nm/°C, compared with that of the un-filled device, which is 9.8 pm/°C. For the RI response, the liquid-filled structure achieves sensitivity of 12,005 nm/RIU in the range between 1.448 and 1.450, slightly higher than the 11,920 nm/RIU achieved by the un-filled one. The proposed sensor exhibits the advantages of simple structure, high sensitivity and low cost, which may find potential applications in physical and chemical sensing.
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http://dx.doi.org/10.3390/s20010135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982897PMC
December 2019

Liquid-Crystal-Filled Side-hole Fiber for High-Sensitivity Temperature and Electric Field Measurement.

Micromachines (Basel) 2019 Nov 10;10(11). Epub 2019 Nov 10.

Guangdong and Hong Kong Joint Research Centre for Optical Fibre Sensors, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

We propose a highly sensitive sensor based on a nematic liquid-crystal-filled side-hole fiber. The liquid crystal is precisely filled into an air hole of the optical fiber using a method of manually gluing in the fusion splicer. Due to the coupling between the liquid crystal waveguide and the fiber core, multiple response dips appear in the transmission spectrum of the device. When an external temperature or electric field variation is applied to the liquid crystal and its refractive index changes, the transmission spectrum of this device will shift accordingly. Temperature and electric field response tests were performed on the device in the experiment, and the obtained temperature and electric field sensitivities were as high as -1.5 nm/°C and 3.88 nm/V, respectively. For the exhibited advantages of being easy to manufacture, low cost, and high sensitivity, the proposed sensor is very promising for actual application in temperature or weak electric field monitoring.
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http://dx.doi.org/10.3390/mi10110761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915413PMC
November 2019

Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway.

J Ethnopharmacol 2020 Jan 18;246:112243. Epub 2019 Sep 18.

Guangdong Province Research Centre for Chinese Integrative Medicine Against Metabolic Disease, China; Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), China; Guangdong TCM Key Laboratory for Metabolic Diseases, China; The Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, China. Electronic address:

Ethnopharmacological Relevance: Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease.

Aim Of The Study: To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms.

Materials And Methods: The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope.

Results: LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist.

Conclusions: EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.
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http://dx.doi.org/10.1016/j.jep.2019.112243DOI Listing
January 2020

Gamma models for estimating the odds ratio for a skewed biomarker measured in pools and subject to errors.

Biostatistics 2021 04;22(2):250-265

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, USA.

Measuring a biomarker in pooled samples from multiple cases or controls can lead to cost-effective estimation of a covariate-adjusted odds ratio, particularly for expensive assays. But pooled measurements may be affected by assay-related measurement error (ME) and/or pooling-related processing error (PE), which can induce bias if ignored. Building on recently developed methods for a normal biomarker subject to additive errors, we present two related estimators for a right-skewed biomarker subject to multiplicative errors: one based on logistic regression and the other based on a Gamma discriminant function model. Applied to a reproductive health dataset with a right-skewed cytokine measured in pools of size 1 and 2, both methods suggest no association with spontaneous abortion. The fitted models indicate little ME but fairly severe PE, the latter of which is much too large to ignore. Simulations mimicking these data with a non-unity odds ratio confirm validity of the estimators and illustrate how PE can detract from pooling-related gains in statistical efficiency. These methods address a key issue associated with the homogeneous pools study design and should facilitate valid odds ratio estimation at a lower cost in a wide range of scenarios.
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http://dx.doi.org/10.1093/biostatistics/kxz028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035988PMC
April 2021

Classifying Depression Severity in Recovery From Major Depressive Disorder via Dynamic Facial Features.

IEEE J Biomed Health Inform 2020 03 23;24(3):815-824. Epub 2019 Jul 23.

Major depressive disorder is a common psychiatric illness. At present, there are no objective, non-verbal, automated markers that can reliably track treatment response. Here, we explore the use of video analysis of facial expressivity in a cohort of severely depressed patients before and after deep brain stimulation (DBS), an experimental treatment for depression. We introduced a set of variability measurements to obtain unsupervised features from muted video recordings, which were then leveraged to build predictive models to classify three levels of severity in the patients' recovery from depression. Multiscale entropy was utilized to estimate the variability in pixel intensity level at various time scales. A dynamic latent variable model was utilized to learn a low-dimensional representation of factors that describe the dynamic relationship between high-dimensional pixels in each video frame and over time. Finally, a novel elastic net ordinal regression model was trained to predict the severity of depression, as independently rated by standard rating scales. Our results suggest that unsupervised features extracted from these video recordings, when incorporated in an ordinal regression predictor, can discriminate different levels of depression severity during ongoing DBS treatment. Objective markers of patient response to treatment have the potential to standardize treatment protocols and enhance the design of future clinical trials.
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http://dx.doi.org/10.1109/JBHI.2019.2930604DOI Listing
March 2020

Dynamic regression with recurrent events.

Biometrics 2019 12 12;75(4):1264-1275. Epub 2019 Sep 12.

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Recurrent events often arise in follow-up studies where a subject may experience multiple occurrences of the same event. Most regression models with recurrent events tacitly assume constant effects of covariates over time, which may not be realistic in practice. To address time-varying effects, we develop a dynamic regression model to target the mean frequency of recurrent events. We propose an estimation procedure which fully exploits observed data. Consistency and weak convergence of the proposed estimator are established. Simulation studies demonstrate that the proposed method works well, and two real data analyses are presented for illustration.
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http://dx.doi.org/10.1111/biom.13105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895398PMC
December 2019

Genetic relationships among sperm quality traits of Duroc boars collected during the summer season.

Anim Reprod Sci 2019 Jul 24;206:85-92. Epub 2019 May 24.

University of Nebraska-Lincoln, Department of Animal Science, Lincoln, NE, USA. Electronic address:

The goals of the study were to estimate the heritability and repeatability of boar sperm quality traits during the summer season, estimate phenotypic and genetic correlations between sperm quality traits, and assess the effect of these traits on total number born (TNB). Semen samples were collected and individually processed from Duroc boars (n = 363) from May through October 2017. Single sire litter information was available for 121 of the boars. Heritability, repeatability, genetic correlations, and phenotypic correlations were estimated for and among the following traits: total percentage of motile cells (MOT), total percentage of progressively motile cells (PROG), percentage of cells with a distal droplet (DIST), percentage of cells with a proximal droplet (PROX), percentage of cells with a bent tail (BENT), percentage of cells with a distal midpiece reflex (DMR), mean sperm head elongation (ELON), and total sperm cells per ejaculate (TOTSP). Heritability estimates ranged from 0.08 to 0.24 and repeatability estimates ranged from 0.21 to 0.62. The phenotypic and genetic correlations between sperm motility traits and morphological defects indicated a negative relationship. Sperm morphological defects had positive phenotypic and genetic correlations with each other. Total sperm per ejaculate showed positive genetic correlations with the motility traits. Positive phenotypic and genetic correlations existed between ELON and the motility traits. Total sperm motility (P <  0.001) positively affected TNB while DIST (P < 0.001), PROX (P < 0.001), BENT (P = 0.05) and DMR (P = 0.002) negatively affected TNB. Results indicate genetic selection could enhance sperm quality during the summer season in boars.
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http://dx.doi.org/10.1016/j.anireprosci.2019.05.012DOI Listing
July 2019

A genome-wide single nucleotide polymorphism and copy number variation analysis for number of piglets born alive.

BMC Genomics 2019 Apr 27;20(1):321. Epub 2019 Apr 27.

Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.

Background: In this study we integrated the CNV (copy number variation) and WssGWAS (weighted single-step approach for genome-wide association) analyses to increase the knowledge about number of piglets born alive, an economically important reproductive trait with significant impact on production efficiency of pigs.

Results: A total of 3892 samples were genotyped with the Porcine SNP80 BeadChip. After quality control, a total of 57,962 high-quality SNPs from 3520 Duroc pigs were retained. The PennCNV algorithm identified 46,118 CNVs, which were aggregated by overlapping in 425 CNV regions (CNVRs) ranging from 2.5 Kb to 9718.4 Kb and covering 197 Mb (~ 7.01%) of the pig autosomal genome. The WssGWAS identified 16 genomic regions explaining more than 1% of the additive genetic variance for number of piglets born alive. The overlap between CNVR and WssGWAS analyses identified common regions on SSC2 (4.2-5.2 Mb), SSC3 (3.9-4.9 Mb), SSC12 (56.6-57.6 Mb), and SSC17 (17.3-18.3 Mb). Those regions are known for harboring important causative variants for pig reproductive traits based on their crucial functions in fertilization, development of gametes and embryos. Functional analysis by the Panther software identified 13 gene ontology biological processes significantly represented in this study such as reproduction, developmental process, cellular component organization or biogenesis, and immune system process, which plays relevant roles in swine reproductive traits.

Conclusion: Our research helps to improve the understanding of the genetic architecture of number of piglets born alive, given that the combination of GWAS and CNV analyses allows for a more efficient identification of the genomic regions and biological processes associated with this trait in Duroc pigs. Pig breeding programs could potentially benefit from a more accurate discovery of important genomic regions.
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http://dx.doi.org/10.1186/s12864-019-5687-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487013PMC
April 2019

Chinese Medicine Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress.

Evid Based Complement Alternat Med 2019 3;2019:6378786. Epub 2019 Mar 3.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory against Metabolic Diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China.

Objective: To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms.

Methods: We used a cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h.

Result: The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group.

Conclusion: FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected -cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.
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http://dx.doi.org/10.1155/2019/6378786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421024PMC
March 2019

High-sensitivity gas pressure sensor based on hollow-core photonic bandgap fiber Mach-Zehnder interferometer.

Opt Express 2018 Nov;26(23):30108-30115

We propose and experimentally demonstrate a highly sensitive gas pressure sensor based on a near-balanced Mach-Zehnder interferometer (MZI) and constructed by hollow-core photonic bandgap fiber (HC-PBF) in this paper. The MZI is simply constructed by fusion splicing two HC-PBFs, which are of slightly different lengths, between two 3-dB couplers. The two output ends of each coupler are approximately equal in length, to ensure that the optical path variations of the MZI only result from the differences in the lengths between the two HC-PBFs. To apply the MZI for gas pressure sensing, a femtosecond laser is employed to drill a micro-channel in one of the two HC-PBF arms. The experiment result shows that the proposed MZI based gas pressure sensor achieves an ultrahigh sensitivity, up to 2.39 nm/kPa, which is two orders of magnitude higher than that of the previously reported MZI-based gas pressure sensors. Additionally, the effects resulting from the absolute length and relative length of the two HC-PBFs on gas pressure sensing performance are also investigated experimentally and theoretically, respectively. The ultra-high sensitivity and ease of fabrication make this device suitable for gas pressure sensing in the field of industrial and environmental safety monitoring.
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http://dx.doi.org/10.1364/OE.26.030108DOI Listing
November 2018

Logistic regression with a continuous exposure measured in pools and subject to errors.

Stat Med 2018 11 18;37(27):4007-4021. Epub 2018 Jul 18.

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.

In a multivariable logistic regression setting where measuring a continuous exposure requires an expensive assay, a design in which the biomarker is measured in pooled samples from multiple subjects can be very cost effective. A logistic regression model for poolwise data is available, but validity requires that the assay yields the precise mean exposure for members of each pool. To account for errors, we assume the assay returns the true mean exposure plus a measurement error (ME) and/or a processing error (PE). We pursue likelihood-based inference for a binary health-related outcome modeled by logistic regression coupled with a normal linear model relating individual-level exposure to covariates and assuming that the ME and PE components are independent and normally distributed regardless of pool size. We compare this approach with a discriminant function-based alternative, and we demonstrate the potential value of incorporating replicates into the study design. Applied to a reproductive health dataset with pools of size 2 along with individual samples and replicates, the model fit with both ME and PE had a lower AIC than a model accounting for ME only. Relative to ignoring errors, this model suggested a somewhat higher (though still nonsignificant) adjusted log-odds ratio associating the cytokine MCP-1 with risk of spontaneous abortion. Simulations modeled after these data confirm validity of the methods, demonstrate how ME and particularly PE can reduce the efficiency advantage of a pooling design, and highlight the value of replicates in improving stability when both errors are present.
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http://dx.doi.org/10.1002/sim.7891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204302PMC
November 2018

Mechanism and Characteristics of Humidity Sensing with Polyvinyl Alcohol-Coated Fiber Surface Plasmon Resonance Sensor.

Sensors (Basel) 2018 Jun 25;18(7). Epub 2018 Jun 25.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

A surface plasmon resonance (SPR) sensor based on a side-polished single mode fiber coated with polyvinyl alcohol (PVA) is demonstrated for relative humidity (RH) sensing. The SPR sensor exhibits a resonant dip in the transmission spectrum in ambient air after PVA film coating, and the resonant wavelength shifts to longer wavelengths as the thickness of the PVA film increases. When RH changes, the resonant dip of the sensor with different film-thicknesses exhibits interesting characteristics for optical spectrum evolution. For sensors with initial wavelengths between 550 nm and 750 nm, the resonant dip shifts to longer wavelengths with increasing RH. The averaged sensitivity increases firstly and then drops, and shows a maximal sensitivity of 1.01 nm/RH%. Once the initial wavelength of the SPR sensor exceeds 850 nm, an inflection point of the resonant wavelength shift can be observed with RH increasing, and the resonant dip shifts to shorter wavelengths for RH values exceeding this point, and sensitivity as high as −4.97 nm/RH% can be obtained in the experiment. The sensor is expected to have potential applications in highly sensitive and cost effective humidity sensing.
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http://dx.doi.org/10.3390/s18072029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068613PMC
June 2018

[Geographic spatial pattern of digestive system cancers in Yiwu city].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2017 May;46(5):537-545

Ocean College, Zhejiang University, Zhoushan 316021, Zhejiang Province, China.

Objective: To analyze the geographic spatial patterns and risk areas of main digestive system cancers in Yiwu city.

Methods: Newly diagnosed cases of esophageal, gastric and colorectal cancer during 2010-2014 were obtained from Yiwu Center for Disease Control and Prevention (CDC). The household registration population data in 2013 were obtained from public security bureau. Hierarchy clustering and partitioning regionalization method was used to generate geographic units. Global Moran's I was used to evaluate whether cancer incidence was significantly clustered in space, Anselin Local Moran's I was used to identify statistically significant hot spots, cold spots, and spatial outliers, and Spatial Scan Statistics was implemented to analyze the relative risk of cancers in different areas.

Results: The 5-year average incidence of esophageal, gastric and colorectal cancers were 9.99/100 000, 34.01/100 000 and 31.46/100 000, respectively. Males showed significantly higher incidence than females. The incidence was heterogeneous throughout the study area. Spatial Scan analysis revealed that southern Yiwu presented a significantly higher male esophageal cancer (=1.78) and gastric cancer (=1.87) risk. The central area of Yiwu showed a significantly lower female esophageal cancer risk (=0.00) and male stomach cancer risk (=0.63) and the northern Yiwu exhibited a significantly lower female colorectal cancer risk (=0.48).

Conclusions: The incidence of main digestive tract cancers shows a heterogeneous distribution in Yiwu city.
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May 2017

Highly sensitive surface plasmon resonance biosensor based on a low-index polymer optical fiber.

Opt Express 2018 Feb;26(4):3988-3994

A highly sensitive refractive index sensor based on surface plasmon resonance in a side-polished low-index polymer optical fiber is proposed for biosensing. Benefitting from the low refractive index of the fiber core, the sensitivity of the device can reach ~44567 nm/RIU theoretically for aqueous solutions, at the expense of a lowered upper detection limit that is down to ~1.340. The sensor is fabricated by coating 55-nm-thick Au-film on the polished surface of a graded-index perfluorinated polymer optical fiber. Results show that the sensor exhibits a sensitivity of ~22779 nm/RIU at 1.335 with a figure of merit of 61.2. When employed for glucose sensing, the sensor presents an averaged sensitivity of 24.50 nm/wt%, or 0.46 nm/mM. This device is expected to have potential applications in cost-effective bio- and chemical-sensing.
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http://dx.doi.org/10.1364/OE.26.003988DOI Listing
February 2018

Magnetic resonance imaging safety in nonconditional pacemaker and defibrillator recipients: A meta-analysis and systematic review.

Heart Rhythm 2018 07 17;15(7):1001-1008. Epub 2018 Feb 17.

Department of Medicine, Section of Cardiac Electrophysiology, Emory University School of Medicine, Atlanta, Georgia.

Background: Recommendations regarding performance of magnetic resonance imaging (MRI) in non-MRI conditional pacemaker and defibrillator recipients are evolving. Previous studies have suggested low adverse event rates with MRI in nonconditional cardiac implantable electronic device (CIED) recipients, but low power limits optimal characterization of risk.

Objective: The purpose of this study was to perform a systematic review and meta-analysis to characterize the clinical risk associated with MRI in CIED recipients in order to improve power.

Methods: PubMed and CINAHL indexed articles from 1990 to 2017 were queried. A random effects model was used for meta-analysis of continuous variables. Safety outcomes were evaluated with descriptive statistics.

Results: Seventy studies of non-MRI conditional devices undergoing MRI were identified, allowing for analysis of 5099 patients who underwent a total of 5908 MRI studies. Heterogeneity in lead parameter changes was observed within studies, although smaller variances were noted between studies. All lead characteristics and battery voltages showed very small, clinically insignificant changes when assessed as a pooled cohort, although cases of clinically relevant outcomes were also noted (lead failure 3, implantable cardioverter-defibrillator shock 1, electrical reset 94). Electrical resets were found only in older devices. Defibrillator function was unchanged, and inappropriate shocks were avoided with pre-MRI programming changes.

Conclusion: This review demonstrated low lead failure and clinical event rates in non-MRI conditional pacemaker and defibrillator recipients undergoing MRI. Observed changes were small and interstudy variance was low, suggesting that the composite event rates offer a reasonable estimate of true effect. The observed adverse events reinforce the need for ongoing vigilance and caution, particularly with older devices.
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http://dx.doi.org/10.1016/j.hrthm.2018.02.019DOI Listing
July 2018

Restoration of Monotonicity Respecting in Dynamic Regression.

Authors:
Yijian Huang

J Am Stat Assoc 2017 30;112(518):613-622. Epub 2017 Mar 30.

Professor, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322.

Dynamic regression models, including the quantile regression model and Aalen's additive hazards model, are widely adopted to investigate evolving covariate effects. Yet lack of monotonicity respecting with standard estimation procedures remains an outstanding issue. Advances have recently been made, but none provides a complete resolution. In this article, we propose a novel adaptive interpolation method to restore monotonicity respecting, by successively identifying and then interpolating nearest monotonicity-respecting points of an original estimator. Under mild regularity conditions, the resulting regression coefficient estimator is shown to be asymptotically equivalent to the original. Our numerical studies have demonstrated that the proposed estimator is much more smooth and may have better finite-sample efficiency than the original as well as, when available as only in special cases, other competing monotonicity-respecting estimators. Illustration with a clinical study is provided.
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http://dx.doi.org/10.1080/01621459.2016.1149070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800531PMC
March 2017

Surface plasmon resonance biosensor based on gold-coated side-polished hexagonal structure photonic crystal fiber.

Opt Express 2017 Aug;25(17):20313-20322

The refractive index sensing characteristics of the side-polished photonic crystal fiber (PCF) surface plasmon resonance (SPR) sensor are detailed investigated in this paper. We used the finite element method (FEM) to study the influences of the side-polished depth, air hole size, lattice constant, and the refractive index (RI) of the PCF material on sensing performance. The simulation results show that the side-polished depth, air hole size, lattice pitch have significant influence on the coupling strength between core mode and surface plasmon polaritons (SPPs), but have little influence on sensitivity; the coupling strength and sensitivity will significant increase with the decrease of RI of the PCF material. The sensitivity of the D-shaped PCF sensor is obtained to be as high as 21700 nm/RIU in the refractive index environment of 1.33-1.34, when the RI of the PCF material is controlled at 1.36. It revealed a new method of making ultra-high sensitivity SPR fiber sensor. Then we experimental demonstrated a SPR refractive sensor based on the side-polished single mode PCF and investigated the sensing performance. The experimental results of the plasmon resonance wavelength sensitivity agree well with the theoretical results. The presented gold-coated D-shaped PCF SPR sensor could be used as a simple, cost-effective, high sensitivity device in bio-chemical detection.
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http://dx.doi.org/10.1364/OE.25.020313DOI Listing
August 2017

Cox regression with dependent error in covariates.

Biometrics 2018 03 6;74(1):118-126. Epub 2017 Jul 6.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, U.S.A.

Many survival studies have error-contaminated covariates due to the lack of a gold standard of measurement. Furthermore, the error distribution can depend on the true covariates but the structure may be difficult to characterize; heteroscedasticity is a common manifestation. We suggest a novel dependent measurement error model with minimal assumptions on the dependence structure, and propose a new functional modeling method for Cox regression when an instrumental variable is available. This proposal accommodates much more general error contamination than existing approaches including nonparametric correction methods of Huang and Wang (2000, Journal of the American Statistical Association 95, 1209-1219; 2006, Statistica Sinica 16, 861-881). The estimated regression coefficients are consistent and asymptotically normal, and a consistent variance estimate is provided for inference. Simulations demonstrate that the procedure performs well even under substantial error contamination. Illustration with a clinical study is provided.
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http://dx.doi.org/10.1111/biom.12741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756534PMC
March 2018

A Minority of Patients Newly Diagnosed with AIDS Are Started on Antiretroviral Therapy at the Time of Diagnosis in a Large Public Hospital in the Southeastern United States.

J Int Assoc Provid AIDS Care 2017 Mar/Apr;16(2):174-179. Epub 2017 Feb 15.

1 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Prompt antiretroviral therapy (ART) initiation after AIDS diagnosis, in the absence of certain opportunistic infections such as tuberculosis and cryptococcal meningitis, delays disease progression and death, but system barriers to inpatient ART initiation at large hospitals in the era of modern ART have been less studied. We reviewed hospitalizations for persons newly diagnosed with AIDS at Grady Memorial Hospital in Atlanta, Georgia in 2011 and 2012. Individual- and system-level variables were collected. Logistic regression models were used to estimate the odds ratios (ORs) for ART initiation prior to discharge. With Georgia Department of Health surveillance data, we estimated time to first clinic visit, ART initiation, and viral suppression. In the study population (n = 81), ART was initiated prior to discharge in 10 (12%) patients. Shorter hospital stay was significantly associated with lack of ART initiation at the time of HIV diagnosis (8 versus 24 days, OR: 1.14, 95% confidence interval: 1.04-1.25). Reducing barriers to ART initiation for newly diagnosed HIV-positive patients with short hospital stays may improve time to viral suppression.
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http://dx.doi.org/10.1177/2325957417692679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192024PMC
December 2017

Characterization and management of long runs of homozygosity in parental nucleus lines and their associated crossbred progeny.

Genet Sel Evol 2016 11 24;48(1):91. Epub 2016 Nov 24.

Department of Animal Science, North Carolina State University, Raleigh, NC, 27695-7627, USA.

Background: In nucleus populations, regions of the genome that have a high frequency of runs of homozygosity (ROH) occur and are associated with a reduction in genetic diversity, as well as adverse effects on fitness. It is currently unclear whether, and to what extent, ROH stretches persist in the crossbred genome and how genomic management in the nucleus population might impact low diversity regions and its implications on the crossbred genome.

Methods: We calculated a ROH statistic based on lengths of 5 (ROH5) or 10 (ROH10) Mb across the genome for genotyped Landrace (LA), Large White (LW) and Duroc (DU) dams. We simulated crossbred dam (LA × LW) and market [DU × (LA × LW)] animal genotypes based on observed parental genotypes and the ROH frequency was tabulated. We conducted a simulation using observed genotypes to determine the impact of minimizing parental relationships on multiple diversity metrics within nucleus herds, i.e. pedigree-(A), SNP-by-SNP relationship matrix or ROH relationship matrix. Genome-wide metrics included, pedigree inbreeding, heterozygosity and proportion of the genome in ROH of at least 5 Mb. Lastly, the genome was split into bins of increasing ROH5 frequency and, within each bin, heterozygosity, ROH5 and length (Mb) of ROH were evaluated.

Results: We detected regions showing high frequencies of either ROH5 and/or ROH10 across both LW and LA on SSC1, SSC4, and SSC14, and across all breeds on SSC9. Long haplotypes were shared across parental breeds and thus, regions of ROH persisted in crossbred animals. Averaged across replicates and breeds, progeny had higher levels of heterozygosity (0.0056 ± 0.002%) and lower proportion of the genome in a ROH of at least 5 Mb (-0.015 ± 0.003%) than their parental genomes when genomic relationships were constrained, while pedigree relationships resulted in negligible differences at the genomic level. Across all breeds, only genomic data was able to target low diversity regions.

Conclusions: We show that long stretches of ROH present in the parents persist in crossbred animals. Furthermore, compared to using pedigree relationships, using genomic information to constrain parental relationships resulted in maintaining more genetic diversity and more effectively targeted low diversity regions.
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http://dx.doi.org/10.1186/s12711-016-0269-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123398PMC
November 2016

Time Course of Subsequent Shocks After Initial Implantable Cardioverter-Defibrillator Discharge and Implications for Driving Restrictions.

JAMA Cardiol 2016 05;1(2):181-8

Cardiology Division, Department of Medicine, Emory University School of Medicine, Emory University Hospital Midtown, Atlanta, Georgia.

Importance: Although guidelines recommend driving restrictions for 3 to 6 months after appropriate implantable cardioverter-defibrillator (ICD) shocks, contemporary data to support these recommendations are lacking.

Objective: To define the time course of subsequent shocks after an initial ICD discharge.

Design, Setting, And Participants: Retrospective analysis of a nationwide cohort of 14 230 ICD recipients enrolled in a remote monitoring program. Participants underwent ICD implantation from October 1, 2008, to December 31, 2013, and experienced at least 1 shock. The risk of driving after an ICD shock was estimated using the risk for harm (RH) formula, and an annual RH of less than 5 events per 100 000 ICD recipients was deemed safe. The likelihood of loss of consciousness associated with an ICD shock was estimated using a cautious value of 32% and an estimate of 14% based on contemporary data. Data were extracted and analyzed from December 17, 2014, to October 31, 2015.

Main Outcomes And Measures: Time course of subsequent shocks after an initial ICD discharge.

Results: Of 73 503 ICD recipients who underwent remote monitoring, 14 230 (19.4%) experienced at least 1 ICD shock and were included in this analysis (10 870 men [76.4%]; 3360 women [23.6%]; median age at device implantation, 68 years; interquartile range [IQR], 60-76 years). The cumulative incidence of receiving a second shock was 14.5% (IQR, 13.9%-15.1%) at 1 month and 28.7% (IQR, 27.9%-29.5%) at 6 months. The time from implantation to initial shock had an inverse association with the likelihood of receiving a second shock (lowest quartile of time at 6 months, 31.6% [95% CI, 30.2%-33.2]; highest quartile of time at 6 months, 25.3% [95% CI, 23.8%-26.9%]). The number of ICD therapy zones was also significantly associated with the incidence of a second shock (1 therapy zone, 20.8% [95% CI, 19.4%-22.3%] at 3 months to 51.5% [95% CI, 48.5%-53.7%] at 3 years; 3 therapy zones, 26.9% [95% CI, 24.8%-29.0%] at 3 months to 57.3% [95% CI, 54.1%-60.5%] at 3 years). When a likelihood of loss of consciousness of 32% associated with an ICD shock was used, the RH while driving fell below the accepted threshold at 4 to 6 months after an initial shock. However, when a contemporary estimate for loss of consciousness associated with an ICD shock of 14% was used, the RH fell below the threshold at 1 month after an initial shock.

Conclusions And Relevance: In this large cohort of ICD recipients, the incidence of a second shock after an initial ICD discharge was lower than previously reported and depended on several programmed ICD variables. These data, with future research to derive contemporary estimates of the likelihood of fatality resulting from an ICD shock while driving, should support the development of evidence-based guidelines for driving restrictions in ICD recipients.
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http://dx.doi.org/10.1001/jamacardio.2015.0386DOI Listing
May 2016

Generalizing Quantile Regression for Counting Processes with Applications to Recurrent Events.

J Am Stat Assoc 2016 5;111(513):145-156. Epub 2016 May 5.

Departments of Nutritional Sciences, Pediatrics, and Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706 ( ).

In survival analysis, quantile regression has become a useful approach to account for covariate effects on the distribution of an event time of interest. In this paper, we discuss how quantile regression can be extended to model counting processes, and thus lead to a broader regression framework for survival data. We specifically investigate the proposed modeling of counting processes for recurrent events data. We show that the new recurrent events model retains the desirable features of quantile regression such as easy interpretation and good model flexibility, while accommodating various observation schemes encountered in observational studies. We develop a general theoretical and inferential framework for the new counting process model, which unifies with an existing method for censored quantile regression. As another useful contribution of this work, we propose a sample-based covariance estimation procedure, which provides a useful complement to the prevailing bootstrapping approach. We demonstrate the utility of our proposals via simulation studies and an application to a dataset from the US Cystic Fibrosis Foundation Patient Registry (CFFPR).
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http://dx.doi.org/10.1080/01621459.2014.995795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872875PMC
May 2016
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