Intradermal DNA vaccine delivery using vacuum-controlled, needle-free electroporation.

Intradermal delivery of DNA vaccines via electroporation (ID-EP) has shown clinical promise, but the use of needle electrodes is typically required to achieve consistent results. Here, delivery of a DNA vaccine targeting the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is achieved using noninvasive intradermal vacuum-EP (ID-VEP), which functions by pulling a small volume of skin tissue into a vacuum chamber containing noninvasive electrodes to perform EP at the injection site. Gene expression and immunogenicity correlated with EP parameters and vacuum chamber geometry in guinea pigs. ID-VEP generated potent humoral and cellular immune responses across multiple studies, while vacuum (without EP) greatly enhanced localized transfection but did not improve immunogenicity. Because EP was performed noninvasively, the only treatment site reaction observed was transient redness, and ID-VEP immune responses were comparable to a clinical needle-based ID-EP device. The ID-VEP delivery procedure is straightforward and highly repeatable, without any dependence on operator technique. This work demonstrates a novel, reliable, and needle-free delivery method for DNA vaccines.

Machine learning prediction of the total duration of invasive and non-invasive ventilation During ICU Stay.

Predicting the duration of ventilation in the ICU helps in assessing the risk of ventilator-induced lung injury, ensuring sufficient oxygenation, and optimizing resource allocation. Prior models provided a prediction of total duration without distinguishing between invasive and non-invasive ventilation. This work proposes two independent gradient boosting regression models for predicting the duration of invasive and non-invasive ventilation based on commonly available ICU features. These models are trained on 2.6 million patient stays across 350 US hospitals between 2010 to 2019. The mean absolute error (MAE) for the prediction of duration was 2.08 days for invasive ventilation and 0.36 days for non-invasive ventilation. The total ventilation duration predicted by our model had MAE of 2.38 days, which outperformed the gold standard (APACHE) with MAE of 3.02 days. The feature importance analysis of the trained models showed that, for invasive ventilation, high average heart rate, diagnosis of respiratory infection and admissions from locations other than the operating room were associated with longer ventilation durations. For non-invasive ventilation, higher respiratory rates and having any GCS measurement were associated with longer durations.

Improving ICU Risk Predictive Models Through Automation Designed for Resiliency Against Documentation Bias.

OBJECTIVES: Electronic health records enable automated data capture for risk models but may introduce bias. We present the Philips Critical Care Outcome Prediction Model (CCOPM) focused on addressing model features sensitive to data drift to improve benchmarking ICUs on mortality performance. DESIGN: Retrospective, multicenter study of ICU patients randomized in 3:2 fashion into development and validation cohorts. Generalized additive models (GAM) with features designed to mitigate biases introduced from documentation of admission diagnosis, Glasgow Coma Scale (GCS), and extreme vital signs were developed using clinical features representing the first 24 hours of ICU admission. SETTING: eICU Research Institute database derived from ICUs participating in the Philips eICU telecritical care program. PATIENTS: A total of 572,985 adult ICU stays discharged from the hospital between January 1, 2017, and December 31, 2018, were included, yielding 509,586 stays in the final cohort; 305,590 and 203,996 in development and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model discrimination was compared against Acute Physiology and Chronic Health Evaluation (APACHE) IVa/IVb models on the validation cohort using the area under the receiver operating characteristic (AUROC) curve. Calibration assessed by actual/predicted ratios, calibration-in-the-large statistics, and visual analysis. Performance metrics were further stratified by subgroups of admission diagnosis and ICU characteristics. Historic data from two health systems with abrupt changes in Glasgow Coma Scale (GCS) documentation were assessed in the year prior to and after data shift. CCOPM outperformed APACHE IVa/IVb for ICU mortality (AUROC, 0.925 vs 0.88) and hospital mortality (AUROC, 0.90 vs 0.86). Better calibration performance was also attained among subgroups of different admission diagnoses, ICU types, and over unique ICU-years. The CCOPM provided more stable predictions compared with APACHE IVa within an external cohort of greater than 120,000 patients from two health systems with known changes in GCS documentation. CONCLUSIONS: These mortality risk models demonstrated excellent performance compared with APACHE while appearing to mitigate bias introduced through major shifts in GCS documentation at two large health systems. This provides evidence to support using automated capture rather than trained personnel for capture of GCS data used in benchmarking ICUs on mortality performance.

Accuracy and efficiency of digitally fabricated all-ceramic crowns from conventional impressions and intraoral scans: A single-blind clinical randomized controlled trial.

PURPOSE: To evaluate the accuracy of intraoral scanners by comparing the marginal fit of 70 all-ceramic crowns fabricated from both conventional impressions and intraoral scans. MATERIALS AND METHODS: A total of 70 posterior teeth requiring single-crown restorations randomly underwent either intraoral scanning or conventional impression-taking followed by laboratory scanning of the casts in a parallel-group RCT. Subsequently, 70 monolithic all-ceramic crowns were CAD/CAM fabricated; only the impression technique differed. Marginal fit, internal fit, adjustment time required for insertion and occlusal contacts, and visual analog scale (VAS) scores assessing dentists' satisfaction with all of the crowns were clinically evaluated by a blinded and calibrated examiner. Data were analyzed using independent-samples t test and likelihood ratio test or Fisher exact test. All tests were performed with α = .05. RESULTS: The mean marginal fit with intraoral scanning (57.94 ± 22.51 µm) was better than with diagnostic cast scanning (82.98 ± 21.72 µm). The difference was statistically significant (P = .000). The differences in internal fit, adjustment time for crown insertion and occlusal contacts, and VAS scores were also significant, and the secondary outcomes were in favor of intraoral scanning. CONCLUSION: Within the limitations of this clinical trial, CAD/CAM-fabricated single-tooth restorations in the posterior region produced by an intraoral scanning technique using TRIOS was found to be a more accurate and efficient alternative to restorations based on conventional impressions in combination with the laboratory scanning technique.

Impact of different axial wall designs on the fracture strength and stress distribution of ceramic restorations in mandibular first molar.

BACKGROUND: The purpose of this study was to investigate the fracture strength and stress distribution of four ceramic restorations. METHODS: Forty human mandibular first molars were collected and randomized into four groups after establishing the distal defect: full crown group with 4 mm axial wall height (AWH) (FC4); short AWH crown group with 2 mm AWH (SC2); occlusal veneer group with 0 mm AWH (OV0); occlusal distal veneer group with only the distal surface prepared, and 4 mm AWH (OD4). The teeth were prepared according to the groups and the ceramic restorations were completed using celtra duo ceramic blocks. The ceramic thickness of the occlusal surface is about 1.5 mm and the edge is about 1 mm. The failure load values and fracture modes of each group were detected by mechanical test in vitro. According to the groups to establish three-dimensional finite element analysis (FEA) models, a 600 N loading force was applied vertically using a hemispherical indenter with a diameter of 6 mm. and compare the stress distribution under the condition of different restorations. RESULTS: In vitro mechanical tests showed that the failure load values were SC2 (3232.80 ± 708.12 N) > OD4 (2886.90 ± 338.72 N) > VO0 (2133.20 ± 376.15 N) > FC4(1635.40 ± 413.05 N). The failure load values of the short AWH crown and occlusal distal veneer were significantly higher than that of occlusal veneer and full crown (P<0.05). The fracture modes of the full crown and occlusal veneer groups were mainly ceramic fractures and some were restorable tooth fractures. The short AWH crown and occlusal distal veneer groups presented with three fracture modes, the proportion of non-restorable tooth fracture was higher. The results of FEA show that under the spherical loading condition, the stress of ceramic was concentrated in the contact area of the loading head, the maximum von Mises stress values were FC4 (356.2 MPa) > VO0 (214.3 MPa) > OD4 (197.9 MPa) > SC2 (163.1 MPa). The stress of enamel was concentrated in the area where the remaining enamel was thinner, the maximum von Mises stress values was OD4 (246.2 MPa) ≈ FC4 (212.4 MPa) > VO0 (61.8 MPa) ≈ SC2 (45.81 MPa). The stress of dentin is concentrated in the root furcation and the upper third region of the root. However, stress concentration was observed at the tooth cervix in the full crown. CONCLUSION: Under certain conditions, the occlusal distal veneer shows better performance than the full crown.

Reliability of Cusp Angulation Using Three-Dimensional Digital Models: A Preliminary In Vitro Study.

BACKGROUND: Dental cusp angulation provides valuable insights into chewing efficiency and prosthesis safety. Artificial intelligence-enabled computing of cusp angles has potential important value, but there is currently no reliable digital measurement method as a cornerstone. OBJECTIVES: To establish a digital method for measuring cusp angles and investigate inter-rater and intra-rater reliabilities. METHODS: Two cusp angles (angles α and ß) of the first molar were measured on 21 plaster casts using a goniometer and on their corresponding digital models using PicPick software after scanning with a CEREC Bluecam three-dimensional (3D) intraoral scanner. Means ± standard deviations, as well as intraclass correlation coefficients (ICCs) and Pearson's correlation coefficients (PCCs) were calculated, and repeated measures analysis of variance was performed. The Bland-Altman method was used to calculate the difference and mean degree values of two measurement methods from both examiners, and the Bland-Altman diagram was drawn using MedCalc software. RESULTS: When the examiner was experienced, angle α was 139.19° ± 13.86°, angle ß was 19.25° ± 6.86°, and a very strong positive correlation between the two methods was found (r > 0.9; p < 0.001). No significant difference between the two methods was found using the repeated measures analysis of variance (p > 0.05). The Bland-Altman diagram showed that the two methods were highly consistent. For inter-rater assessments, the ICC and PCC values of the cusp angulation using the digital method were all higher than the corresponding values measured on traditional casts. For intra-rater assessments, the ICC values of cusp angulation using the digital method were higher than the corresponding values measured on traditional plaster casts for both examiners. However, repeated measurements of the angle ß of the inter-examiners revealed significant differences (p < 0.05) for both methods. CONCLUSIONS: Cusp angulation using 3D digital models is a clinical option and appears to improve the reliability of cusp angulation compared with measuring plaster casts using a goniometer. This variability was still evident when measuring small cusp angles using the digital model for inexperienced examiners.

Red Blood Cell Product Transfusion Thresholds and Clinical Outcomes.

OBJECTIVE: To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay. DESIGN: An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders. SETTING AND PATIENTS: This study included all adult patients discharged from 1 of 203 adult ICUs from 32 US health-care systems. The patients were from community hospitals, tertiary, and academic medical centers. INTERVENTION: Transfusion of allogenic packed RBCs or whole blood was prescribed at the discretion of the treating clinicians. MEASUREMENTS AND MAIN RESULTS: We found that 15% of adult ICU patients are transfused RBC products, and most transfusions for hemodynamically stable patients are administered above the guideline-specified pretransfusion Hb threshold of 7 g/dL. Hemodynamically stable patients transfused below this threshold were significantly more likely to survive their ICU stay than those not transfused (odds ratio [OR] 0.59, 95% confidence interval [CI], 0.43-0.81; P = .001), and patients transfused at thresholds above 9 g/dL were less likely to survive their ICU stay than those not transfused. Patients of the acute blood loss group who were transfused appeared to benefit or were not harmed by transfusion. CONCLUSION: Conservative RBC product transfusion practices for groups that are targeted by guidelines are justified by outcomes observed in clinical practice. This study provides evidence for the liberal administration of RBC products to critically ill adults with acute blood loss based on association with lower risk of mortality.

Cardiologist perceptions of family-centred rounds in cardiovascular clinical care.

Objective: Few data exist regarding physician attitudes and implementation of family-centred rounds (FCR) in cardiovascular care. This study aimed to assess knowledge and attitudes among cardiologists and cardiology fellows regarding barriers and benefits of FCRs. Methods: An electronic, web-based questionnaire was nationally distributed to cardiology fellows and attending cardiologists. Results: In total, 118 subjects were surveyed, comprising cardiologists (n=64, 54%) and cardiology fellows (n=54, 46%). Overall, 61% of providers reported participating in FCRs and 64% felt family participation on rounds benefits the patient. Both fellows and cardiologists agreed that family rounds eased family anxiety (fellows, 63%; cardiologists, 56%; p=0.53), improved communication between the medical team and the patient and family (fellows, 78%; cardiologists, 61%; p=0.18) and improved patient safety (fellows, 59%; cardiologists, 47%; p=0.43). Attitudes regarding enhancement of trainee education were similar (fellows, 69%; cardiologists, 55%; p=0.19). Fellows and cardiologists felt that family increased the duration of rounds (fellows, 78%; cardiologists, 80%; p=0.18) and led to less efficient rounds (fellows, 54%; cardiologists, 58%; p=0.27). Conclusion: The majority of cardiologists and fellows believed that FCRs benefited families, communication and patient safety, but led to reduced efficiency and longer duration of rounds.

Evaluation of ICU Risk Models Adapted for Use as Continuous Markers of Severity of Illness Throughout the ICU Stay.

OBJECTIVES: Evaluate the accuracy of different ICU risk models repurposed as continuous markers of severity of illness. DESIGN: Nonintervention cohort study. SETTING: eICU Research Institute ICUs using tele-ICU software calculating continuous ICU Discharge Readiness Scores between January 2013 and March 2016. PATIENTS: Five hundred sixty-one thousand four hundred seventy-eight adult ICU patients with an ICU length of stay between 4 hours and 30 days. INTERVENTIONS: Not available. MEASUREMENTS AND MAIN RESULTS: Hourly Acute Physiology and Chronic Health Evaluation IV, Sequential Organ Failure Assessment, and Discharge Readiness Scores were calculated beginning hour 4 of the ICU stay. Primary outcome was the area under the receiver operating characteristic curve for the mean score with ICU mortality. Secondary outcomes included area under the receiver operating characteristic curves for ICU mortality with admission, median, maximum and last scores, and for death within 24 hours. The trajectories of each score were visualized by plotting the hourly averages against time in the ICU, stratified by mortality and length of stay. The area under the receiver operating characteristic curves for mean Acute Physiology and Chronic Health Evaluation, Sequential Organ Failure Assessment, and Discharge Readiness Scores were 0.90 (0.89-0.90), 0.86 (0.86-0.86), and 0.94 (0.94-0.94), respectively. The area under the receiver operating characteristic curves for hourly Acute Physiology and Chronic Health Evaluation, Sequential Organ Failure Assessment, and Discharge Readiness Scores predicting 24-hour mortality were 0.81 (0.81-0.81), 0.76 (0.76-0.76), and 0.86 (0.86-0.86). Discharge Readiness Scores had a higher area under the receiver operating characteristic curve than both Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment for each metric. Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores increased throughout the first 24 hours in both survivors and nonsurvivors; Discharge Readiness Scores continuously decreased in survivors and temporarily decreased before increasing by hour 36 in nonsurvivors with longer length of stays. CONCLUSIONS: Acute Physiology and Chronic Health Evaluation, Sequential Organ Failure Assessment, and Discharge Readiness Scores all have relatively high discrimination for ICU mortality when used continuously; Discharge Readiness Scores tended to have slightly higher area under the receiver operating characteristic curves for each endpoint. These findings validate the use of these models on a population level for continuous risk adjustment in the ICU, although Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment appear slower to respond to improvements in patient status than Discharge Readiness Scores, and Discharge Readiness Scores may reflect physiologic improvement from interventions, potentially underestimating risk.

Reliability study in the measurement of the cusp inclination angle of a chairside digital model / 华西口腔医学杂志

OBJECTIVE@#This study aims to evaluate the reliability of the software Picpick in the measurement of the cusp inclination angle of a digital model.@*METHODS@#Twenty-one trimmed models were used as experimental objects. The chairside digital impression was then used for the acquisition of 3D digital models, and the software Picpick was employed for the measurement of the cusp inclination of these models. The measurements were repeated three times, and the results were compared with a gold standard, which was a manually measured experimental model cusp angle. The intraclass correlation coefficient (ICC) was calculated.@*RESULTS@#The paired t test value of the two measurement methods was 0.91. The ICCs between the two measurement methods and three repeated measurements were greater than 0.9. The digital model achieved a smaller coefficient of variation (9.9%).@*CONCLUSIONS@#The software Picpick is reliable in measuring the cusp inclination of a digital model.

Clinical and radiographic evaluation of pulpectomy in primary teeth: a 18-months clinical randomized controlled trial.

BACKGROUND: To avoid untoward changes when primary teeth are replaced by permanent teeth, resorption of the material used in primary teeth root canal filling should occur at the same rate as root resorption. The Aim of this study was to compare the success rates of a mixed primary root canal filling (MPRCF, ingredients: zinc oxide-eugenol [ZOE], iodoform, calcium hydroxide) to those of ZOE and Vitapex in pulpectomised primary molars. METHODS: One hundred and sixty primary molars from 155 children (average age 5.88 ± 1.27 years) underwent two-visit pulpectomy using one of the three materials. The clinical and radiographic findings at 6, 12 and 18 months were assessed. RESULTS: At 6 and 12 months, the MPRCF and ZOE success rates were 100%. The Vitapex group showed clinical success rate and radiographic success rate of 100 and 94.5% at 6 months, and 80.4 and 60.7% at 12 months. The 18-month clinical success rates of the MPRCF, ZOE and Vitapex were 96.2, 92.2 and 71.4% and radiographic success rates were 92.5, 88.2 and 53.6%, respectively. There was a statistically significant difference in the success rates between MPRCF and Vitapex and no significant differences between MPRCF and ZOE. More MPRCF were resorbed at same rate with roots than ZOE and Vitapex. Early resorption of root filling resulted in more failure. CONCLUSIONS: The mixture of ZOE, iodoform and calcium hydroxide can be considered an effective root canal filling material in pulp involved primary teeth and had no adverse effect on tooth replacement. TRIAL REGISTRATION: ChiCTR-TRC-14004938 . Registered 13 July 2014.

Five-Year Trends of Critical Care Practice and Outcomes.

BACKGROUND: Longitudinal analyses of large, detailed adult critical care datasets provide insights into practice trends and generate useful outcome and process benchmarks. METHODS: Data representing 991,571 consecutive critical care visits to 160 US adult ICUs from 2009 to 2013 from the eICU Research Institute clinical practice database were used to quantitate patient characteristics, APACHE IV-based acuity predictions, treatments, and outcomes. Analyses for changes over time were performed for patient characteristics, entry and discharge locations, primary admission diagnosis, treatments, adherence to consensus ICU best practices, length of stay (LOS), and inpatient mortality. RESULTS: We detected significant trends for increasing age, BMI, and risk of mortality, higher frequency of admission from an ED and stepdown unit, and more frequent hospital discharge to substance abuse centers and skilled nursing facilities. Significantly more patients were admitted for sepsis, emphysema, coma, congestive heart failure, diabetic ketoacidosis, and fewer were admitted for asthma, unspecified chest pain, coronary artery bypass graft, and stroke care. The frequency of noninvasive mechanical ventilation and adherence to critical care best practices significantly increased, whereas the duration of renal replacement therapies, frequency of transfusions, antimicrobial use, critical care complications, LOS, and inpatient mortality decreased. CONCLUSIONS: Analyses of patients, practices, and outcomes from a large geographically dispersed sample of adult ICUs revealed trends of increasing age and acuity, higher rates of adherence to best practice, use of noninvasive mechanical ventilation, and decreased use of antimicrobials, transfusions, and duration of renal replacement therapies. Acuity-adjusted LOS and in hospital mortality decreased.

The Obesity Paradox Is Not Observed in Critically Ill Patients on Early Enteral Nutrition.

OBJECTIVES: To investigate the association between body mass index and mortality in a large, ICU population and determine if the relationship is observed among a subgroup of patients ordered early enteral nutrition. DESIGN: Retrospective cohort study within a national clinical mixed ICU database of patients admitted between January 1, 2008, and June 30, 2015. SETTING: Initial ICU admissions among patients monitored by tele-ICU programs and recorded in the Philips eICU Research Institute database. PATIENTS: A total of 1,042,710 adult patient stays with ICU length of stay more than 24 hours, of which 74,771 were ordered enteral nutrition within the first 48 hours. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patient stays from 409 ICUs were included. The average age, Acute Physiology and Chronic Health Evaluation IV score, and hospital mortality were 63.6 years, 56.7, and 9.0%, respectively. Hospital mortality among body mass index categories was estimated by multivariable modified Poisson regression models. Compared with the body mass index category 25.0-29.9 kg/m, hospital mortality was higher among underweight (body mass index, < 18.5; relative risk, 1.35; 95% CI, 1.32-1.39), normal weight (body mass index, 18.5-24.9; relative risk, 1.10; 95% CI, 1.09-1.12), and the extremely obese (body mass index, ≥ 50.0; relative risk, 1.10; 95% CI, 1.05-1.15). However, the risk was not statistically different from patients with body mass index 30.0-49.9 kg/m. Among patients ordered early enteral nutrition, the risk of mortality in the body mass index category 25.0-29.9 kg/m was not statistically different from those in the normal weight or extremely obese groups. CONCLUSIONS: A survival advantage for overweight and obese patients was observed in this large cohort of critically ill patients. However, among those ordered early enteral nutrition, the survival disadvantage for body mass index categories less than 25.0 kg/m was minimal or unobservable when compared with higher body mass index categories.

[Composition and Environmental Adaptation of Microbial Community in Shibahe Copper Tailing in Zhongtiao Mountain in Shanxi].

In order to reveal the effects of heavy metal pollution on microbial community compositions and microbial community diversity in tailing area,we conducted an experiment by examining the microbial community in tailing water,sediments and tailing sand in Shibahe copper tailing in Zhongtiao Mountain.Differences in microbial community compositions in different habitats and their relationships with environmental parameters were analyzed.The results showed that the richness and diversity of microbial community were the largest in tailing sand,but the lowest in tailing water.Microbial community compositions were similar between tailing water and sediments.There were significant positive correlations between the relative abundance of the dominant family (Sphingomonadaceae) and contents of heavy metals (Cd,Cu,Mn,Ni,Pb,Zn),while there were significant negative correlations between relative abundances of aulobacteraceae, Methylobacteriaceae, Nocardioidaceae, Microbacteriaceae, Micrococcaceae, Streptococcaceae and Paenibacillaceae and heavy metal contents.It showed that most of the bacteria were inhibited by heavy metals,but Sphingomonadaceae had a higher tolerance to heavy metals which may indicate that it has a potential for remediation of heavy metal contamination.

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT): Design of a Phase IIb, placebo-controlled, double-blind, randomized clinical trial of doxycycline for the reduction of growth of small abdominal aortic aneurysm.

OBJECTIVES: The Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT) is a Phase IIb randomized, placebo-controlled clinical trial, testing doxycycline (100mg bid) for inhibition of growth in the greatest transverse, orthogonal diameter of small abdominal aortic aneurysms (AAA). METHODS: We will enroll 258 patients, ≥55years of age who have AAA, men: 3.5-5.0cm and women: 3.5-4.5cm on CT scans confirmed centrally. The primary outcome is growth in maximal transverse, orthogonal diameter from baseline to 24-month follow-up. Secondary analyses address doxycycline effects on clinical events, aneurysm volume, and biomarkers. Primary analysis will be performed according to the principle of intention-to-treat accounting for death and ruptures by use of normal scores in analysis of covariance. At the time of the data file reported, 200 subjects have been randomized. We started enrollment in mid-2013 and will complete enrollment by mid-2016. RESULTS: Participant average age=70.9years, (SD=7.6years) and maximum transverse diameter=4.3cm for men (SD=0.4) and 4.0cm for women (SD=0.3). CONCLUSION: N-TA(3)CT is a critical experiment to determine whether doxycycline reduces growth of small AAA and systemic markers of inflammation previously seen in bench experiments and observational human studies to be associated with AAA growth. Our patient population baseline measurements agree with the design assumptions supporting our expectation of 90% power or greater to reject a null hypothesis in favor of an alternative hypothesis when growth is reduced by at least 40%. REGISTRATION: clinicaltrials.gov #NCT01756833.