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991.
Nathaniel J. Rhodes Joseph L. Kuti David P. Nicolau Scott Van Wart Anthony M. Nicasio Jiajun Liu Benjamin J. Lee Michael N. Neely Marc H. Scheetz 《Antimicrobial agents and chemotherapy》2016,60(3):1401-1410
The percentage of time that free drug concentrations remain above the MIC (fT>MIC) that is necessary to prevent mortality among cefepime-treated patients with Gram-negative bloodstream infections (GNBSI) is poorly defined. We conducted a retrospective study of adult patients with GNBSI. Eligible cases were frequency matched to ensure categorical representation from all MICs. Organism, MIC, infection source, gender, age, serum creatinine, weight, antibiotic history, and modified APACHE II score were collected from hospital records. Two population pharmacokinetic models (models 1 and 2) were used to impute exposures over the first 24 h in each patient from mean model parameters, covariates, and dosing history. From the imputed exposures, survival thresholds for fT>MIC were identified using classification and regression tree (CART) analysis and analyzed as nominal variables for univariate and multivariate regressions. A total of 180 patients were included in the analysis, of whom 13.9% died and 86.1% survived. Many patients (46.7% [n = 84/180]) received combination therapy with cefepime. Survivors had higher mean (standard deviation [SD]) fT>MIC than those who died (model 1, 74.2% [29.6%] versus 52.1% [33.8%], P < 0.001; model 2, 85.9% [24.0%] versus 64.4% [31.4%], P < 0.001). CART identified fT>MIC threshold values for greater survival according to models 1 and 2 at >68% and >74%, respectively. Survival was improved for those with fT>MIC of >68% (model 1 adjusted odds ratio [aOR], 7.12; 95% confidence interval [CI], 1.90 to 26.7; P = 0.004) and >74% (model 2 aOR, 6.48; 95% CI, 1.90 to 22.1) after controlling for clinical covariates. Similarly, each 1% increase in cefepime fT>MIC resulted in a 2% improvement in multivariate survival probability (P = 0.015). Achieving a cefepime fT>MIC of 68 to 74% was associated with a higher odds of survival for patients with GNBSI. Regimens targeting this exposure should be aggressively pursued. 相似文献
992.
Patrick R. Gonzales Erica F. Andersen Teneille R. Brown Vanessa L. Horner Juli Horwitz Catherine W. Rehder Natasha L. Rudy Nathaniel H. Robin Erik C. Thorland 《Genetics in medicine》2022,24(2):255-261
Genomic testing, including single-nucleotide variation (formerly single-nucleotide polymorphism)–based chromosomal microarray and exome and genome sequencing, can detect long regions of homozygosity (ROH) within the genome. Genomic testing can also detect possible uniparental disomy (UPD). Platforms that can detect ROH and possible UPD have matured since the initial American College of Medical Genetics and Genomics (ACMG) standard was published in 2013, and the detection of ROH and UPD by these platforms has shown utility in diagnosis of patients with genetic/genomic disorders. The presence of these segments, when distributed across multiple chromosomes, may indicate a familial relationship between the proband’s parents. This technical standard describes the detection of possible consanguinity and UPD by genomic testing, as well as the factors confounding the inference of a specific parental relationship or UPD. Current bioethical and legal issues regarding detection and reporting of consanguinity are also discussed. 相似文献
993.
994.
Ezra N. Teitelbaum Nathaniel J. Soper John E. Pandolfino Peter J. Kahrilas Lubomyr Boris Frédéric Nicodème Zhiyue Lin Eric S. Hungness 《Surgical endoscopy》2014,28(10):2840-2847
Background
For laparoscopic Heller myotomy (LHM), the optimal myotomy length proximal to the esophagogastric junction (EGJ) is unknown. In this study, we used a functional lumen imaging probe (FLIP) to measure EGJ distensibility changes resulting from variable proximal myotomy lengths during LHM and peroral esophageal myotomy (POEM).Methods
Distensibility index (DI) (defined as the minimum cross-sectional area at the EGJ divided by pressure) was measured with FLIP after each operative step. During LHM and POEM, each patient’s myotomy was performed in two stages: first, a myotomy ablating only the EGJ complex was created (EGJ-M), extending from 2 cm proximal to the EGJ, to 3 cm distal to it. Next, the myotomy was lengthened 4 cm further cephalad to create an extended proximal myotomy (EP-M).Results
Measurements were performed in 12 patients undergoing LHM and 19 undergoing POEM. LHM resulted in an overall increase in DI (1.6 ± 1 vs. 6.3 ± 3.4 mm2/mmHg, p < 0.001). Creation of an EGJ-M resulted in a small increase (1.6–2.3 mm2/mmHg, p < 0.01) and extension to an EP-M resulted in a larger increase (2.3–4.9 mm2/mmHg, p < 0.001). This effect was consistent, with 11 (92 %) patients experiencing a larger increase after EP-M than after EGJ-M. Fundoplication resulted in a decrease in DI and deinsufflation an increase. POEM resulted in an increase in DI (1.3 ± 1 vs. 9.2 ± 3.9 mm2/mmHg, p < 0.001). Both creation of the submucosal tunnel and performing an EGJ-M increased DI, whereas lengthening of the myotomy to an EP-M had no additional effect. POEM resulted in a larger overall increase from baseline than LHM (7.9 ± 3.5 vs. 4.7 ± 3.3 mm2/mmHg, p < 0.05).Conclusions
During LHM, an EP-M was necessary to normalize distensibility, whereas during POEM, a myotomy confined to the EGJ complex was sufficient. In this cohort, POEM resulted in a larger overall increase in EGJ distensibility. 相似文献995.
Lawrence S. Engel Jessie P. Buckley Gong Yang Linda M. Liao Jaya Satagopan Antonia M. Calafat Charles E. Matthews Qiuyin Cai Bu-Tian Ji Hui Cai Stephanie M. Engel Mary S. Wolff Nathaniel Rothman Wei Zheng Yong-Bing Xiang Xiao-Ou Shu Yu-Tang Gao Wong-Ho Chow 《Environmental health perspectives》2014,122(7):733-740
Background: Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations.Objectives: We sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults.Methods: We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997–2006 from 50 participants of the Shanghai Women’s Health Study cohort and during 2002–2006 from 50 participants of the Shanghai Men’s Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs).Results: Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54–0.60, SCC = 0.43–0.56), but lower for other analytes (ICC = 0.20–0.29). Reproducibility among women was low (ICC = 0.13–0.39), but increased when restricted to morning-only urine samples.Conclusions: Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women.Citation: Engel LS, Buckley JP, Yang G, Liao LM, Satagopan J, Calafat AM, Matthews CE, Cai Q, Ji BT, Cai H, Engel SM, Wolff MS, Rothman N, Zheng W, Xiang YB, Shu XO, Gao YT, Chow WH. 2014. Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men. Environ Health Perspect 122:733–740; http://dx.doi.org/10.1289/ehp.1306830 相似文献
996.
997.
Evangelina López de Maturana Stephen J. Chanok Antoni C. Picornell Nathaniel Rothman Jesús Herranz M. Luz Calle Montserrat García‐Closas Gaëlle Marenne Angela Brand Adonina Tardón Alfredo Carrato Debra T. Silverman Manolis Kogevinas Daniel Gianola Francisco X. Real Núria Malats 《Genetic epidemiology》2014,38(5):467-476
To build a predictive model for urothelial carcinoma of the bladder (UCB) risk combining both genomic and nongenomic data, 1,127 cases and 1,090 controls from the Spanish Bladder Cancer/EPICURO study were genotyped using the HumanHap 1M SNP array. After quality control filters, genotypes from 475,290 variants were available. Nongenomic information comprised age, gender, region, and smoking status. Three Bayesian threshold models were implemented including: (1) only genomic information, (2) only nongenomic data, and (3) both sources of information. The three models were applied to the whole population, to only nonsmokers, to male smokers, and to extreme phenotypes to potentiate the UCB genetic component. The area under the ROC curve allowed evaluating the predictive ability of each model in a 10‐fold cross‐validation scenario. Smoking status showed the highest predictive ability of UCB risk (AUCtest = 0.62). On the other hand, the AUC of all genetic variants was poorer (0.53). When the extreme phenotype approach was applied, the predictive ability of the genomic model improved 15%. This study represents a first attempt to build a predictive model for UCB risk combining both genomic and nongenomic data and applying state‐of‐the‐art statistical approaches. However, the lack of genetic relatedness among individuals, the complexity of UCB etiology, as well as a relatively small statistical power, may explain the low predictive ability for UCB risk. The study confirms the difficulty of predicting complex diseases using genetic data, and suggests the limited translational potential of findings from this type of data into public health interventions. 相似文献
998.
999.
Nathaniel A. Bates Kevin R. Ford Gregory D. Myer Timothy E. Hewett 《Clinical biomechanics (Bristol, Avon)》2013
Background
Rapid impulse loads imparted on the lower extremity from ground contact when landing from a jump may contribute to ACL injury prevalence in female athletes. The drop jump and drop landing tasks enacted in the first and second landings of drop vertical jumps, respectively, have been shown to elicit separate neuromechanical responses. We examined the first and second landings of a drop vertical jump for differences in landing phase duration, time to peak force, and rate of force development.Methods
239 adolescent female basketball players completed drop vertical jumps from an initial height of 31 cm. In-ground force platforms and a three dimensional motion capture system recorded force and positional data for each trial.Findings
Between the first and second landing, rate of force development experienced no change (P > 0.62), landing phase duration decreased (P = 0.01), and time to peak ground reaction force increased (P < 0.01). Side-by-side asymmetry in rate of force development was not present in either landing (P > 0.12).Interpretation
The current results have important implications for the future assessment of ACL injury risk behaviors. Rate of force development remained unchanged between first and second landings from equivalent fall height, while time to peak reaction force increased during the second landing. Neither factor was dependent on the total time duration of landing phase, which decreased during the second landing. Shorter time to peak force may increase ligament strain and better represent the abrupt joint loading that is associated with ACL injury risk. 相似文献1000.
Byron P. Olson Nathaniel I. Matter Marwood N. Ediger Edward L. Hull John D. Maynard 《Journal of diabetes science and technology》2013,7(4):990-1000