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Aim of study This study aims to quantify the relative impact of Dispatcher-Initiated Telephone cardiopulmonary resuscitation (TCPR) on survival and survival with favorable functional outcome after out-of-hospital cardiac arrest (OHCA) in a population of patients served by multiple emergency dispatch centers and more than 130 emergency medical services (EMS) agencies. Methods We conducted a retrospective, observational study of EMS-treated adult (≥18 years) patients with OHCA of presumed cardiac origin in Arizona, between January 1, 2011, and December 31, 2014. We compared survival and functional outcome among three distinct groups of OHCA patients: those who received no CPR before EMS arrival (no CPR group); those who received BCPR before EMS arrival and prior to or without telephone CPR instructions (BCPR group); and those who received TCPR (TCPR group). Results In this study, 2310 of 4391 patients met the study criteria (median age, 62 years; IQR 50, 74; 1540 male). 32.8% received no CPR, 23.8% received Bystander-Initiated CPR and 43.4% received TCPR. Overall survival was 11.5%. Using no CPR as the reference group, the multivariate adjusted odds ratio for survival at hospital discharge was 1.51 (95% confidence interval [CI], 1.04, 2.18) for BCPR and 1.64 (95% CI, 1.16, 2.30) for TCPR. The multivariate adjusted odds ratio of favorable functional outcome at discharge was 1.58 (95% CI 1.05, 2.39) for BCPR and 1.56 (95% CI, 1.06, 2.31) for TCPR. Conclusion TCPR is independently associated with improved survival and improved functional outcome after OHCA.

The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR deacetylation, vitamin-d-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kidney and TE85 bone cells, co-transfection of low amounts (1-5ng) of a SIRT1-expression vector elicits a reproducible and statistically significant enhancement (1.3- to 2.6-fold) in transcription mediated by VDREs from the CYP3A4 and cyp24a1 genes, where the magnitude of response to 1,25D-ligand is 6- to 30-fold. Inhibition of SIRT1 via EX-527, or utilization of a SIRT1 loss-of-function mutant (H363Y), resulted in abrogation of SIRT1-mediated VDR potentiation. Studies with a novel, non-acetylatable VDR mutant (K413R) showed that the mutant VDR possesses enhanced responsiveness to 1,25D, in conjunction with reduced, but still significant, sensitivity to exogenous SIRT1, indicating that acetylation of lysine 413 is relevant, but that other acetylated residues in VDR contribute to modulation of its activity. We conclude that the acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This regulatory loop is reversed by SIRT1-catalyzed deacetylation of VDR to amplify VDR signaling and 1,25D actions.

Objectives To determine whether the relationship between anthropometric measurements of obesity and mortality varies according to age, race, and ethnicity in older women. Design Prospective cohort study of multiethnic postmenopausal women. Setting Women's Health Initiative (WHI) observational study and clinical trials in 40 clinics. Participants Postmenopausal women aged 50–79 participating in WHI (N = 161,808). Measurements Baseline height, weight, and waist circumference (WC) were measured, and body mass index (BMI) was calculated based on height and weight. Demographic, health, and lifestyle data from a baseline questionnaire were used as covariates. The outcome was adjudicated death (n = 18,320) during a mean follow-up of 11.4 ± 3.2 years. Results Hazard ratios (HRs) and 95% confidence intervals (95% CIs) indicated that ethnicity and age modified (P < .01) the relationship between obesity and mortality. Underweight was associated with higher mortality, but overweight or slight obesity was not a risk factor for mortality in most ethnic groups except for Hispanic women in the obesity I category (HR = 1.42, 95% CI = 1.04–1.95). BMI was not or was only weakly associated with mortality in individuals aged 70–79 (HR = 0.90, 95% CI = 0.85–0.95 for overweight; HR = 0.98, 95 CI = 0.92–1.06 for obese I; HR = 1.11, 95% CI = 1.00–1.23 for obese II; HR = 1.08, 95% CI = 0.92–1.26 for obese III). In contrast, higher central obesity measured using WC was consistently associated with higher mortality in all groups. Conclusion Underweight is a significant risk factor for mortality in older women, and healthy BMI ranges may need to be specific for age, race, and ethnicity. The findings support a consistent relationship between central obesity and mortality.

Study objective Survival is significantly reduced by either hypotension or hypoxia during the out-of-hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out-of-hospital hypotension and hypoxia separately and in combination. Methods All moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out-of-hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: 200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure Results Among the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death. Conclusion In this statewide analysis of major traumatic brain injury, combined out-of-hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death for patients with both hypotension and hypoxia were more than 2 times greater than for those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current emergency medical services traumatic brain injury treatment guidelines but clearly reveal the need for further study to determine their influence on outcome.

Emergency medical telecommunicators can play a key role in improving outcomes from out-of-hospital cardiac arrest (OHCA) by providing instructions for cardiopulmonary resuscitation (CPR) to callers. Telecommunicators, however, frequently encounter barriers that obstruct the Telephone CPR (TCPR) process. The nature and frequency of these barriers in public and residential locations have not been well investigated. The aim of this study is to identify the barriers to TCPR in public and residential locations.We conducted a retrospective study of audio recordings of EMS-confirmed OHCAs from eight regional 9-1-1 dispatch centers between January 2012 and December 2013.We reviewed 1850 eligible cases (public location OHCAs: N=223 and residential location OHCAs: N=1627). Telecommunicators less frequently encountered barriers such as inability to calm callers in public than in residential locations (2.1% vs 8.5%, p=0.002) or inability to place victims on a hard flat surface (13.9% vs 25.4%, p0.001). However, the barrier where callers were not with patients was more frequently observed in public than in residential locations (11.8% vs 2.7%, p0.001).This study revealed that barriers to TCPR are distributed differently across public and residential locations. Understanding these differences can aid in the development of strategies to enhance bystander CPR and improve overall patient outcomes.

Background The study of circulating biomarkers and their association with disease outcomes has become progressively complex due to advances in the measurement of these biomarkers through multiplex technologies. The Least Absolute Shrinkage and Selection Operator (LASSO) is a data analysis method that may be utilized for biomarker selection in these high dimensional data. However, it is unclear which LASSO-type method is preferable when considering data scenarios that may be present in serum biomarker research, such as high correlation between biomarkers, weak associations with the outcome, and sparse number of true signals. The goal of this study was to compare the LASSO to five LASSO-type methods given these scenarios. Methods A simulation study was performed to compare the LASSO, Adaptive LASSO, Elastic Net, Iterated LASSO, Bootstrap-Enhanced LASSO, and Weighted Fusion for the binary logistic regression model. The simulation study was designed to reflect the data structure of the population-based Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD), specifically the sample size (N = 1000 for total population, 500 for sub-analyses), correlation of biomarkers (0.20, 0.50, 0.80), prevalence of overweight (40%) and obese (12%) outcomes, and the association of outcomes with standardized serum biomarker concentrations (log-odds ratio = 0.05–1.75). Each LASSO-type method was then applied to the TESAOD data of 306 overweight, 66 obese, and 463 normal-weight subjects with a panel of 86 serum biomarkers. Results Based on the simulation study, no method had an overall superior performance. The Weighted Fusion correctly identified more true signals, but incorrectly included more noise variables. The LASSO and Elastic Net correctly identified many true signals and excluded more noise variables. In the application study, biomarkers of overweight and obesity selected by all methods were Adiponectin, Apolipoprotein H, Calcitonin, CD14, Complement 3, C-reactive protein, Ferritin, Growth Hormone, Immunoglobulin M, Interleukin-18, Leptin, Monocyte Chemotactic Protein-1, Myoglobin, Sex Hormone Binding Globulin, Surfactant Protein D, and YKL-40. Conclusions For the data scenarios examined, choice of optimal LASSO-type method was data structure dependent and should be guided by the research objective. The LASSO-type methods identified biomarkers that have known associations with obesity and obesity related conditions.

Background Structural joint pathology on MRI has been found in knees without radiographic evidence of osteoarthritis (OA). We have previously shown that structural abnormalities on MRI may be precursors of disease and associated with the detection of incident radiographic knee OA (ROA) up to 2 years later, and in some circumstances up to seven years later. The prognostic value of structural abnormalities on MRI for knee OA, however, is unknown. Objectives Estimate the probability of incident ROA over 10 years of follow-up, according to structural abnormalities detected on baseline MRIs. Methods A subcohort of participants (862 knees, one knee/person) from the Osteoarthritis Initiative (OAI) with at least one knee at risk of developing ROA (i.e., Kellgren-Lawrence (KL) 0,1 at baseline) was randomly selected. MRI-detected structural features of the knee were assessed by expert readers using the MRI Osteoarthritis Knee Score (MOAKS). Participants underwent bilateral posteroanterior fixed-flexion weight-bearing knee radiography at baseline and annually through year 4, and then every two years until year 10. Radiographs were centrally read for KL grade, with ROA defined as KL≥2. Survival was estimated with the Turnbull non-parametric maximum likelihood estimator, a generalization of Kaplan Meier curves for interval censored data. Survival curves were compared using a log rank permutation test available in the R package interval. Hazard ratios were estimated using Cox models fit using the R package icenReg, designed for interval censored data. Features were considered one at a time, with no adjustments. Results Knees with any of the following structural abnormalities had higher estimated probabilities for the development of radiographic OA within two, four and 10 years of follow-up: effusion-synovitis, Hoffa-synovitis, bone marrow lesions in the medial compartment and whole knee, surface area and full thickness cartilage damage in the medial compartment and whole knee, and medial meniscal extrusion (Table 1). Differences in the probability for the development of ROA within two, four, and 10 years of follow-up were significant (pointwise 95% confidence intervals did not include 0), between knees without the abnormality and knees in the most severe category for all features, with one exception at the two-year follow-up. All of these abnormalities were significantly associated with time to ROA over 10 years of follow-up. Conclusion Our results demonstrate the prognostic value of effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage damage, and meniscal extrusion for the development of ROA up to 10 years later. Future directions include developing a predictive model that incorporates multiple features. Disclosure of Interests C. Kent Kwoh Grant/research support from: EMD Serono and Abbvie, Consultant for: EMD Serono, Fidia, Regulus, GSK, Taiwan Lipopsome Company, Inc, Kolon Tissue Gene, Express Scripts, Frank Roemer Shareholder of: Boston Imaging Core Lab (BICL), LLC., Leena Sharma: None declared, Erin Ashbeck Consultant for: EMD Serono, Chengcheng Hu: None declared, Ali Guermazi Shareholder of: Boston Imaging Core Lab (BICL), LLC., Consultant for: Pfizer, AstraZeneca, MerckSerono, TissueGene, Galapagos and Roche

To compare obstetric and surgical outcomes of transabdominal cerclage (TAC) via laparotomy (TAC-LAP) versus robotic-assisted (TAC-RA) approaches.Retrospective cohort study.An academic medical center.Sixty-nine women with acquired or congenital cervical insufficiency.All women underwent TAC either by laparotomy or robotic-assisted approaches by 2 primary surgeons between January 2003 and July 2018. Women with a preconceptional TAC without a subsequent pregnancy were excluded.A total of 69 women met inclusion criteria in the 15-year study period with 40 in the historical TAC-LAP group and 29 in the TAC-RA group. Gestational age at delivery was similar in the 2 groups (36 weeks 3 days vs 37 weeks; median difference -1 day, 95% confidence interval [CI] -6 to 2, p = .36). There were no differences in birth weight, Apgar scores, neonatal intensive care unit admission, or neonatal survival. Estimated blood loss and length of stay were significantly greater in the TAC-LAP group (50 mL vs 20 mL; median difference 25, 95% CI 5-40, p = .007 and 76 hours vs 3 hours; median difference 71, 95% CI 65-75, p.001, respectively). Operative time was significantly shorter in the TAC-LAP group (65 minutes vs 132 minutes; median difference -64.7, 95% CI -79 to -49, p.001). There was one intra-operative complication and 4 minor postoperative complications in the TAC-LAP group and none observed in the TAC-RA group. All outcomes were similar when comparing postconceptional TAC alone, except there was no longer a difference in blood loss. When comparing pre- versus postconceptional robotic TAC, there were no differences in surgical outcomes.Robotic TAC has similar favorable obstetric outcomes to traditional laparotomy and is associated with reduced blood loss and shorter hospital stays. Despite longer operative times, the robotic group did not experience any intra-operative or postoperative complications, which speaks to the benefits of this minimally invasive approach to TAC.

Emergency service vehicle incidents are a leading cause of firefighter fatalities and are also hazardous to civilian road users. Modifiable driving behaviors may be associated with emergency service vehicle incidents. The goal of this study was to use telematics to identify driving behaviors associated with crashes in the fire service.Forty-three emergency service vehicles in 2 fire departments were equipped with telematics devices (12 in Department A and 31 in Department B). The devices collected vehicle coordinates, speed, and g forces, which were monitored for exceptions to driving rules established by the fire departments regarding speeding, harsh braking, and hard cornering. Fire department administrative reports were used to identify vehicles involved in crashes and merged with daily telematics data. Penalized logistic regression was used to identify driving rules associated with crashes. Least absolute shrinkage and selection operator (LASSO) regression was used to generate a telematics-based risk index for emergency service vehicle incidents.Nearly 1.1 million km of driving data and 44 crashes were recorded among the 2 departments during the study. Harsh braking was associated with increased odds of crash in Department A (odds ratio [OR] = 2.22; 95% confidence interval [CI], 1.09-4.51) and Department B (OR = 1.55; 95% CI, 1.12-2.15). For every kilometer of nonemergency speeding, the odds of crash increased by 35% in Department A (OR = 1.35; 95% CI, 1.03-1.77) and by over 2-fold in Department B (OR = 2.09; 95% CI, 1.19-3.66). In Department B, hard cornering (OR = 1.14; 95% CI, 1.03-1.26) and emergency speeding (OR = 1.65; 95% CI, 1.06-2.57) were also associated with increased odds of crash. The final LASSO risk index model had a sensitivity of 73% and specificity of 57%.Harsh braking and excessive speeding were driving behaviors most associated with crash in the fire service. Telematics may be a useful tool for monitoring driver safety in the fire service.

Conidiation and sexual development are critical for reproduction, dispersal and better-adapted survival in many filamentous fungi. The Neurospora crassa gene ada-6 encodes a Zn(II)2Cys6-type transcription factor, whose deletion resulted in reduced conidial production and female sterility. In this study, we confirmed the positive contribution of ada-6 to conidiation and sexual development by detailed phenotypic characterization of its deletion mutant and the complemented mutant. To understand the regulatory mechanisms of ADA-6 in conidiation and sexual development, transcriptomic profiles generated by RNA-seq from the Δada-6 mutant and wild type during conidiation and sexual development were compared. During conidial development, differential expressed genes (DEGs) between the Δada-6 mutant and wild type are mainly involved in oxidation-reduction process and single-organism metabolic process. Several conidiation related genes are positively regulated by ADA-6, including genes that positively regulate conidiation (fluffy and acon-3), and genes preferentially expressed during conidial development (eas, con-6, con-8, con-10, con-13, pcp-1, and NCU9357), as the expression of these genes were lower in the Δada-6 mutant compared to wild type during conidial development. Phenotypic observation of deletion mutants for other genes with unknown function down-regulated by ada-6 deletion revealed that deletion mutants for four genes (NCU00929, NCU05260, NCU00116, and NCU04813) produced less conidia than wild type. Deletion of ada-6 resulted in female sterility, which might be due to that ADA-6 affects oxidation-reduction process and transmembrane transport process, and positively regulates the transcription of pre-2, poi-2, and NCU05832, three key genes participating in sexual development. In both conidiation and the sexual development process, ADA-6 regulates the transcription of cat-3 and other genes participating in reactive oxygen species production according to RNA-seq data, indicating a role of ADA-6 in oxidative stress response. This was further confirmed by the results that deletion of ada-6 led to hypersensitivity to oxidants H2O2 and menadione. Together, these results proved that ADA-6, as a global regulator, plays a crucial role in conidiation, sexual development, and oxidative stress response of N. crassa.

Background: Higher chest compression release velocity (CCRV) is associated with better outcomes after OHCA. Patient age and gender have been associated with variations in chest wall compliance and compressibility which may impact outcomes. Hypothesis: To evaluate the association between CCRV and OHCA patient age, weight, and gender. Methods: Observational study of prospectively collected OHCA quality improvement data in two suburban EMS agencies in Arizona between 10/1/2008 and 12/31/2016. Patient age and weight were categorized into quartiles for the analysis. CCRV was summarized at each level of the categorical variable by median and inter-quartile range (IQR), and was then compared between different levels by the Kruskal-Wallis test. Results: During the study period, 2,661 OHCA cases were treated. After exclusion criteria, 1,140 cases remained for analysis. Median duration of compressions was 8.70 minutes. Mean CCRV was negatively correlated with age and positively correlated with weight (Table). Male patients exhibited a greater mean CCRV compared to female patients [344.4 mm/s (IQR 307.3-384.6) vs. 331.5 (285.3-385.5), p=0.0133]. Conclusion: Patient characteristics including younger age, male gender, and increased weight were associated with a higher CCRV during OHCA resuscitation.

Background: Traumatic brain injury (TBI) studies with extensive prehospital data linked to trauma center (TC) outcomes have been small. Thus, risk adjusters like age and systolic BP have been treated dichotomously (e.g. age ≥55, SBP Hypothesis: The interactions between age, SBP, and mortality are neither simple nor dichotomous. Methods and Inclusion: Major TBI cases, age ≥10, in EPIC (NIH 1R01NS071049) before TBI guideline implementation (1/07-3/14). Logistic regression was used to associate death with age and lowest EMS SBP, adjusted for confounders, and fitted nonparametrically using penalized thin plate regression splines through the generalized additive model. Results: Included were 13,435 cases (Excl: 6.2% missing data; Med. age 46; 67.8% male). The Figure shows 3D planar images of the associations between adjusted risk of death (vertical axis), age and SBP. Fig A reveals: 1) there is no “hypotension threshold” below 120 mmHg at any age and this inflection point increases to 135 in older adults; 2) the optimal SBP vs outcome “valley” is very broad (e.g. ~120-180 in the young) and increases with age (~135-190 in the elderly). Figs B/C reveal: 1) mortality increases across the entire spectrum of age, 2) in hypotensive cases (SBP linearly with increasing age, 3) in non -hypotensive patients, the adjusted risk of death increases much more rapidly after age 40. Conclusion: Due to the small size of extant EMS studies, the evidence supporting parameters in triage guidelines (e.g. “older adults”) and EMS treatment guidelines (e.g. SBP

Background: The advent of highly sensitive End-Tidal CO2 (ETCO2) sensors allows effective monitoring of intubated patients in many emergency care settings, including EMS. Previous work has explored the use of ETCO2 monitoring in non-intubated patients with sensors placed in the nares. However, nothing is known about the effect of passive oxygen delivery [nasal cannula (NC) or non-rebreather mask (NRB)] on ETCO2 measurement. Objective: To compare ETCO2 measurements in non-intubated Traumatic Brain Injury (TBI) patients receiving O2 via NC vs NRB in the prehospital setting. Methods: A subset of major TBI cases (CDC Barell Matrix Type-1) in the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS-1R01NS071049; ClinicalTrials.gov-NCT01339702) were evaluated 4/13-3/17). Non-intubated cases from 6 EMS agencies providing monitor data (Philips MRx) were included when continuous ETCO2 data were available. Statistics: Two-tailed t test, α = 0.05. Results: The 104 included cases had median age of 50.5 (range: 9-91; male: 67%). 39 (37.5%) received O2 via NC and 65 (62.5%) via NRB. Mean ETCO2: NC cases: 27.7 mmHg (95% CI: 25.7, 29.8); NRB: 30.0 (28.1, 31.8; p=0.132). There were also no significant differences among the mean lowest recorded values (p=0.449) or the mean highest values (p=0.275). Conclusion: We believe this is the first report comparing ETCO2 values based upon the method of passive O2 delivery in non-intubated patients. The minor differences between NC vs NRB-oxygenated patients was neither statistically nor clinically significant. This is surprising since: 1) the O2 flow rates and 2) the open-air (NC) vs mask (NRB) delivery methods are so dramatically different. Future study is needed to identify the clinical implications of using noninvasive ETCO2 measurement as a tool for monitoring ventilatory status and changes in non-intubated TBI (and other) patients.

Background: In hospital-based studies, hypotension (HT, SBP Hypothesis: Prehospital HT is associated with differential effects in MTBI and ITBI and these effects are influenced by the severity of primary brain injury. Methods: Inclusion: TBI cases in the EPIC Study (NIH 1R01NS071049) before TBI guideline implementation (1/07-3/14). ITBI: Major TBI cases (CDC Barell Matrix Type 1) that had no injury with ICD9-based Regional Severity Score [RSS (AIS equivalent)] ≥3 in any other body region. MTBI: Type 1 TBI plus at least one non-head region injury with RSS ≥3. Results: Included were 13,435 cases [Excl: age Conclusion: Among major TBI patients with prehospital HT, those with MTBI were much more likely to die than those with ITBI. However, this association varied dramatically with TBI severity. In mod/severe TBI cases with HT, MTBI mortality was 2.4 times higher than in ITBI. In contrast, in very/extremely severe TBI with HT, there was no identifiable mortality difference. Thus, in cases with substantial potential to survive the primary brain injury (mod/severe), outcome is markedly worse in patients with multisystem injuries. However, in very/extremely severe TBI, non-head region injuries have no apparent association with mortality. This may be because the TBI is the primary factor leading to death in these cases. The main EPIC study is evaluating whether this severity-based difference in “effect” has implications for TBI guideline treatment effectiveness.

Background: End-Tidal CO2 (ETCO2) monitoring is valuable in the management of traumatic brain injury (TBI). In intubated patients it helps prevent hyper/over-ventilation. In non-intubated patients, placing a sensor in the nares allows accurate monitoring of respiratory rate and has other promising uses (e.g. monitoring ETCO2 trends in worsening TBI, COPD, etc). Study Objective: To identify how accurately EMS providers document ETCO2, we compared the values recorded in EMS patient care records (PCR) to monitor data in non-intubated TBI patients. Methods: Cases from 6 EMS agencies reporting continuous monitor data (Philips MRx) in the EPIC Study (NIH 1R01NS071049) were evaluated (4/13-3/17). All ETCO2 data available for this post-hoc review were displayed and accessible to the EMS providers during care. Concordance was defined in two ways (for both highest and lowest ETCO2): ≤5 and ≤3 mmHg difference between the monitor data and PCR-documented values. Results: 106 cases were included [median age: 47 (range: 9-91), 66% male]. The figure shows concordance between PCR documentation and monitor data for both the lowest and highest recorded ETCO2 values. Conclusion: The highest PCR-recorded vs monitor ETCO2 values had excellent concordance for a difference ≤5 mmHg (85.9%) and it was good (76.4%) even when defined at the limits of instrument precision (≤3 for ETCO2 compared to actual pCO2). However, for lowest ETCO2, concordance was very poor (only 42.5% for ≤5). The failure to accurately document low ETCO2 in a “passive-ventilation” setting may also have significant implications for improving ventilatory care among intubated patients because identifying and correcting hypocapnia/hyperventilation in actively-ventilated cases is extraordinarily important. The low concordance rates may be due to the emphasis on discreet, intermittent vital sign documentation rather than ongoing identification and documentation of significant ETCO2 variation.

Myeloid malignancies, including myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia, are characterized by abnormal proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). Reports on analysis of bone marrow samples from patients have revealed a high incidence of mutations in splicing factors in early stem and progenitor cell clones, but the mechanisms underlying transformation of HSPCs harboring these mutations remain unknown. Using ex vivo cultures of primary human CD34+ cells as a model, we find that mutations in splicing factors SRSF2 and U2AF1 exert distinct effects on proliferation and differentiation of HSPCs. SRSF2 mutations cause a dramatic inhibition of proliferation via a G2-M phase arrest and induction of apoptosis. U2AF1 mutations, conversely, do not significantly affect proliferation. Mutations in both SRSF2 and U2AF1 cause abnormal differentiation by skewing granulo-monocytic differentiation toward monocytes but elicit diverse effects on megakaryo-erythroid differentiation. The SRSF2 mutations skew differentiation toward megakaryocytes whereas U2AF1 mutations cause an increase in the erythroid cell populations. These distinct functional consequences indicate that SRSF2 and U2AF1 mutations have cell context-specific effects and that the generation of myeloid disease phenotype by mutations in the genes coding these two proteins likely involves different intracellular mechanisms.

Azoles are the most widely used antifungals for controlling fungal infections in clinic and agriculture. Fungi can adapt to azole stress by rapidly activating the transcription of a number of genes, and some of these genes can elevate resistance to azoles. We had reported the transcription factor CCG-8 as a new regulator in the adaptation to antifungal azole stress in Neurospora crassa and Fusarium verticillioides. In this study, we further investigate the mechanisms by which CCG-8 promotes fungal adaptation to azole stress using N. crassa as a model. While deletion of ccg-8 made N. crassa hypersensitive to azoles, ccg-8 overexpression strain was more resistant to azoles than wild type, which further confirmed the positive role of ccg-8 in the adaptation to antifungal azoles. Liquid chromatography–mass spectrometry analysis showed that deletion of ccg-8 resulted in decrease of ergosterol biosynthesis, and high accumulation of toxic sterol 14α-methyl-3,6-diol and ketoconazole (KTC) in the cells, whereas intracellular accumulation of ketoconazole was decreased in the ccg-8 overexpression strain as compared to wild type. For analyzing the effect of CCG-8 on azole export, we tested the contribution of predicted multidrug transporters to azole resistance and found that CDR4 is the major contributor for azole efflux in N. crassa. Interestingly, overexpression of cdr4 or erg11 in the ccg-8 deletion mutant restored its hypersensitive phenotype and overexpression of cdr4 can reduce the level of intracellular KTC. However, the double mutant of ccg-8 and cdr4 was more sensitive than each single mutant, suggesting that drug efflux pump CDR4 plays less contribution for intracellular azole accumulation in the ccg-8 deletion mutant, and CCG-8 may regulate drug uptake. Together, our results revealed that CCG-8 plays a pivotal role in azole adaptive responses of N. crassa by regulating the drug accumulation in the cells.

Study Objective To investigate the impact of transversus abdominis plane (TAP) blocks on postoperative pain management after laparoscopic hysterectomy. Design A retrospective cohort study. Setting An academic medical center. Patients or Participants All women who underwent laparoscopic or robotic-assisted hysterectomy at a single institution. Interventions Anesthesia delivered TAP block administered in the operating room immediately following laparoscopic hysterectomy between 2018 and 2020. Measurements and Main Results In our initial analysis, we included 115 women who underwent laparoscopic or robotic-assisted hysterectomy. Thirty patients (26%) received a postoperative TAP block and 85 patients (74%) did not receive a TAP block. Demographics, preoperative, and intraoperative variables were similar between the two groups. However, the TAP block group received significantly more intraoperative morphine milliequivalents (MMEs) (75 MMEs versus 60 MMEs, p=0.008) and less local anesthetic administered at the skin incisions and the cervix (p Conclusion Our preliminary results do not show a significant reduction in postoperative opioids or recovery room pain scores for patients who received a TAP block compared to those who did not. Our next step will be to increase our sample size, perform a regression analysis, and complete a sub-analysis of patients with chronic pelvic pain.

BACKGROUND Children undergoing treatment for acute lymphoblastic leukemia (ALL) often present to the emergency department (ED) with a fever. They are at high risk of bacteremia secondary to being immunocompromised. Recent reports indicate that procalcitonin (PCT) is a useful marker of bacteremia in children. OBJECTIVE Our objective was to evaluate the clinical utility of PCT as a rapid marker of bacteremia in children with ALL presenting to the ED with a fever. In addition, we compared the results of PCT with white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). METHODS Retrospective chart reviews were conducted of 492 patients with a total of 735 visits presenting to the ED from January 2009 to June 2012 with fever and a history of ALL where a PCT and a blood culture (BC) were obtained,. Positive BCs determined to be contaminants were excluded. The predictive powers of PCT, WBC, ESR, and CRP for bacteremia were evaluated using the area under the receiver operating characteristic curve with 95% confidence intervals (CI). In addition, each of the 4 markers were also examined in a logistic regression model as a potential predictor of the BC result. RESULTS A total of 735 PCT values were correlated with BC results. There were 76 (10.3%) true-positive BCs. The area under the receiver operating characteristic curve was 0.729 (95% CI, 0.661-0.792) for PCT, 0.685 (95% CI, 0.531-0.823) for ESR, 0.622 (95% CI, 0.460-0.796) for CRP, and 0.567 (95% CI, 0.483-0.649) for WBC. When logistic regression was used, the transformation log PCT was significantly associated with BC result whereas each of the other 3 markers, after appropriate transformation to remove heavy skewness, was not significant (all P > 0.1). A doubling of PCT was associated with an odds ratio of 1.32 for positive BCs (95% CI, 1.15-1.53). CONCLUSIONS Procalcitonin value was significantly associated with positive BC (P < 0.0001). The diagnostic performance of PCT was better than the other markers of inflammation. Its use in the ED in a select population of patients may be of significant value in identifying bacteremia. This has the potential to lead to a decrease in unwarranted use of antibiotics, hospital length of stay, and health care expenditures.

Introduction: Low lean mass (LM) is a risk factor for chronic disease, a major cause of disability and diminished quality of life, and is a heritable trait. However, relatively few specific genetic factors have been identified as potentially influencing this trait. Methods: In this study, we selected 1493 single-nucleotide polymorphisms (SNP) in 155 candidate genes involved in anabolic, catabolic, growth hormone, and other related pathways and examined their association with LM, assessed by dual-energy x-ray absorptiometry, in a sample of 2760 non-Hispanic and Hispanic white postmenopausal women from the Women’s Health Initiative (WHI) Observational Study. We assessed the replication of our top findings in a meta-analysis of 20 genome-wide association studies (n = 38,292) conducted by the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Musculoskeletal Working Group. Results: We identified 32 SNPs that had nominally significant associations with LM in the WHI cohort. In the replication stage, we find that SNP rs2276541 in the activin A receptor, type IIB (ACVR2B), was significantly associated with LM (β = 0.15, P = 2.17 × 10−5). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, myostatin, and has previously been identified in a candidate gene study as a determinant of skeletal muscle mass. Conclusions: Our findings support a previously proposed role of ACVR2B allelic variation as a determinant of muscle mass and extend prior findings in men and women. Additional large-scale studies will be needed to confirm our findings in different populations.

T cell-mediated immunity has the ability to produce durable anti-melanoma responses resulting in improved survival of patients with advanced melanoma. Antigen presentation is a key determinant of T cell responses. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens to CD4+ T cells. However, GILT expression in melanoma has not been defined. We evaluated GILT and MHC class II expression in human primary and metastatic melanomas and nevi using immunohistochemistry. GILT staining in melanocytes was observed in 70% of primary and 58% of metastatic melanomas versus 0% of nevi. When present, the GILT staining intensity in melanocytes was typically faint. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT staining in antigen presenting cells was detected in 100% of primary and metastatic melanomas versus 31% of nevi and was typically intense. GILT expression was increased in antigen presenting cells of primary and metastatic melanomas compared to nevi, whereas MHC class II had equivalent high expression in antigen presenting cells of all melanocytic lesions. GILT staining in keratinocytes was detected in 67% of primary melanomas versus 14% of nevi and 6% of metastatic melanomas. GILT, but not MHC class II, expression was increased in keratinocytes of primary melanomas compared to nevi and metastases. GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective anti-melanoma T cell responses. GILT expression may be a biomarker of immune recognition of melanoma.

Measurement error is well known to cause bias in estimated regression coefficients and a loss of power for detecting associations. Methods commonly used to correct for bias often require auxiliary data. We develop a solution for investigating associations between the change in an imprecisely measured outcome and precisely measured predictors, adjusting for the baseline value of the outcome when auxiliary data are not available. We require the specification of ranges for the reliability or the measurement error variance. The solution allows one to investigate the associations for change and to assess the impact of the measurement error.

The purpose of this article is to describe a statistical approach for predicting a respirator user's fit factor in the future based upon results from initial tests. A statistical prediction model was developed based upon joint distribution of multiple fit factor measurements over time obtained from linear mixed effect models. The model accounts for within-subject correlation as well as short-term (within one day) and longer-term variability. As an example of applying this approach, model parameters were estimated from a research study in which volunteers were trained by three different modalities to use one of two types of respirators. They underwent two quantitative fit tests at the initial session and two on the same day approximately six months later. The fitted models demonstrated correlation and gave the estimated distribution of future fit test results conditional on past results for an individual worker. This approach can be applied to establishing a criterion value for passing an initial fit test to provide reasonable likelihood that a worker will be adequately protected in the future; and to optimizing the repeat fit factor test intervals individually for each user for cost-effective testing.

International Guidelines recommend measurement of end-tidal carbon dioxide (EtCO2) to enhance cardiopulmonary resuscitation (CPR) quality and optimize blood flow during CPR. Numerous factors impact EtCO2 (e.g., ventilation, metabolism, cardiac output), yet few clinical studies have correlated CPR quality and EtCO2 during actual out-of-hospital cardiac arrest (OHCA) resuscitations. The purpose of this study was to describe the association between EtCO2 and CPR quality variables during OHCA.This is an observational study of prospectively collected CPR quality and capnography data from two EMS agencies participating in a statewide resuscitation quality improvement program. CPR quality and capnography data from adult (≥18 years) cardiac resuscitation attempts (10/2008-06/2013) were collected and analyzed on a minute-by-minute basis using RescueNet™ Code Review. Linear mixed effect models were used to evaluate the association between (log-transformed) EtCO2 level and CPR variables: chest compression (CC) depth, CC rate, CC release velocity (CCRV), ventilation rate.Among the 1217 adult OHCA cases of presumed cardiac etiology, 925 (76.0%) had a monitor-defibrillator file with CPR quality data, of which 296 (32.0%) cases had1 minute of capnography data during CPR. After capnography quality review, 66 of these cases (22.3%) were excluded due to uninterpretable capnography, resulting in a final study sample of 230 subjects (mean age 68 years; 69.1% male), with a total of 1581 minutes of data. After adjustment for other CPR variables, a 10 mm increase in CC depth was associated with a 4.0% increase in EtCO2 (p0.0001), a 10 compression/minute increase in CC rate with a 1.7% increase in EtCO2 (p = 0.02), a 10 mm/second increase in CCRV with a 2.8% increase in EtCO2 (p = 0.03), and a 10 breath/minute increase in ventilation rate with a 17.4% decrease in EtCO2 (p0.0001).When controlling for known CPR quality variables, increases in CC depth, CC rate and CCRV were each associated with a statistically significant but clinically modest increase in EtCO2. Given the small effect sizes, the clinical utility of using EtCO2 to guide CPR performance is unclear. Further research is needed to determine the practicality and impact of using real-time EtCO2 to guide CPR delivery in the prehospital environment.

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage. Cancer Prev Res; 9(2); 128–34. ©2015 AACR. See related article by Tsai and Hawk, p. 125

Background Firefighting is a hazardous profession and firefighters suffer workplace injury at a higher rate than most US workers. Decreased physical fitness is associated with injury in firefighters. A physical fitness intervention was implemented among Tucson Fire Department recruit firefighters with the goals of decreasing injury and compensation claims frequency and costs during the recruit academy, and over the subsequent probationary year. Methods Department injury records were analysed and described by body part, injury type and mechanism of injury. Injury and workers’ compensation claims outcomes from the recruit academy initiation through the 12-month probationary period for the intervention recruit class were compared with controls from three historical classes. Results The majority of injuries were sprains and strains (65.4%), the most common mechanism of injury was acute overexertion (67.9%) and the lower extremity was the most commonly affected body region (61.7%). The intervention class experienced significantly fewer injuries overall and during the probationary year (p=0.009), filed fewer claims (p=0.028) and experienced claims cost savings of approximately US$33 000 (2013) from avoided injury and reduced claims costs. The estimated costs for programme implementation were $32 192 leading to a 1-year return on investment of 2.4%. Conclusions We observed reductions in injury occurrence and compensation costs among Probationary Firefighter Fitness (PFF-Fit) programme participants compared with historical controls. The initiation of the PFF-Fit programme has demonstrated promise in reducing injury and claims costs; however, continued research is needed to better understand the programme's potential effectiveness with additional recruit classes and carryover effects into the recruit's career injury potential.

BackgroundThoracic injuries are common in trauma. Approximately one-third will develop a pneumothorax, hemothorax, or hemopneumothorax (HPTX), usually with concomitant rib fractures. Tube thoracostomy (TT) is the standard of care for these conditions, though TTs expose the patient to the risk of infectious complications. The controversy regarding antibiotic prophylaxis at the time of TT placement remains unresolved. This multicenter study sought to reconcile divergent evidence regarding the effectiveness of antibiotics given as prophylaxis with TT placement.MethodsThe primary outcome measures of in-hospital empyema and pneumonia were evaluated in this prospective, observational, and American Association for the Surgery of Trauma multicenter study. Patients were grouped according to treatment status (ABX and NoABX). A 1:1 nearest neighbor method matched the ABX patients with NoABX controls. Multilevel models with random effects for matched pairs and trauma centers were fit for binary and count outcomes using logistic and negative binomial regression models, respectively.ResultsTTs for HPTX were placed in 1887 patients among 23 trauma centers. The ABX and NoABX groups accounted for 14% and 86% of the patients, respectively. Cefazolin was the most frequent of 14 antibiotics prescribed. No difference in the incidence of pneumonia and empyema was observed between groups (2.2% vs 1.5%, p=0.75). Antibiotic treatment demonstrated a positive but non-significant association with risk of pneumonia (OR 1.61; 95% CI: 0.86~3.03; p=0.14) or empyema (OR 1.51; 95% CI: 0.42~5.42; p=0.53).ConclusionThere is no evidence to support the routine use of presumptive antibiotics for post-traumatic TT to decrease the incidence of pneumonia or empyema. More investigation is necessary to balance optimal patient outcomes and antibiotic stewardship.Level of evidenceII Prospective comparative study

To analyze hot news data of a culture experimental area in China, web crawler, text extraction, named entity recognition, word cloud and other technologies are be used in the paper. The news texts are obtained by using Berkeley DB, Scrapy frame and web page text extraction algorithm firstly. The total number of crawled news articles is 6.87 million. Then based on these data, the analysis of news attention and statistics of hot news to the experimental area are conducted by using NLTK's NER technology and Weka tools. And the relevant industry to the experimental were also analyzed. The visual representation of analysis results also is provided in this paper.

Continuous-time Markov models are commonly used to analyze longitudinal transitions between multiple disease states in panel data, where participants' disease states are only observed at multiple time points, and the exact state paths between observations are unknown. However, when covariate effects are incorporated and allowed to vary for different transitions, the number of potential parameters to estimate can become large even when the number of covariates is moderate, and traditional maximum likelihood estimation and subset model selection procedures can easily become unstable due to overfitting. We propose a novel regularized continuous-time Markov model with the elastic net penalty, which is capable of simultaneous variable selection and estimation for large number of parameters. We derive an efficient coordinate descent algorithm to solve the penalized optimization problem, which is fully automatic and data driven. We further consider an extension where one of the states is death, and time of death is exactly known but the state path leading to death is unknown. The proposed method is extensively evaluated in a simulation study, and demonstrated in an application to real-world data on airflow limitation state transitions.

Background This study evaluated the efficacy of a fire department proactive risk management program aimed at reducing firefighter injuries and their associated costs. Methods Injury data were collected for the intervention fire department and a contemporary control department. Workers’ compensation claim frequency and costs were analyzed for the intervention fire department only. Total, exercise, patient transport, and fireground operations injury rates were calculated for both fire departments. Results There was a post-intervention average annual reduction in injuries (13%), workers’ compensation injury claims (30%) and claims costs (21%). Median monthly injury rates comparing the post-intervention to the pre-intervention period did not show statistically significant changes in either the intervention or control fire department. Conclusions Reduced workers’ compensation claims and costs were observed following the risk management intervention, but changes in injury rates were not statistically significant.

Objective Risk management (RM) is a cyclical process of identifying and ranking risks, implementing controls, and evaluating their effectiveness. This study aims to identify effective RM interventions in the U.S. mining industry. Methods RM interventions were identified in four companies representing metal, aggregate, and coal mining sectors. Injury rates were determined using Mine Safety and Health Administration (MSHA) data and changes in injury rates identified through change point analysis. Program implementation costs and associated changes in injury costs were evaluated for select interventions. Results Six of 20 RM interventions were associated with a decline in all injuries and one with a reduction in lost-time injuries, all with a positive return on investment. Conclusion Reductions in injuries and associated costs were observed following implementation of a limited number of specific RM interventions.

Measurement of serum biomarkers by multiplex assays may be more variable as compared to single biomarker assays. Measurement error in these data may bias parameter estimates in regression analysis, which could mask true associations of serum biomarkers with an outcome. The Least Absolute Shrinkage and Selection Operator (LASSO) can be used for variable selection in these high-dimensional data. Furthermore, when the distribution of measurement error is assumed to be known or estimated with replication data, a simple measurement error correction method can be applied to the LASSO method. However, in practice the distribution of the measurement error is unknown and is expensive to estimate through replication both in monetary cost and need for greater amount of sample which is often limited in quantity. We adapt an existing bias correction approach by estimating the measurement error using validation data in which a subset of serum biomarkers are re-measured on a random subset of the study sample. We evaluate this method using simulated data and data from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD). We show that the bias in parameter estimation is reduced and variable selection is improved.

The aim of our study was to assess the impact of coronary angiography (CAG) after out-of-hospital cardiac arrest (OHCA) without ST-elevation (STE).Prospective observational study of adult (age ≥ 18) OHCA of presumed cardiac etiology from 1/01/2010-12/31/2014 admitted to one of 40 recognized cardiac receiving centers within a statewide resuscitation network.Among 11,976 cases, 1881 remained for analysis after exclusions. Of the 1230 non-STE cases, 524 (43%) underwent CAG with resultant PCI in 157 (30%). Survival in non-STE cases was: 56% in cases without CAG; 82% in cases with CAG but without PCI; and 78% in those with PCI (p 0.0001). In cases without STE the aOR for survival with CAG alone was 2.34 (95% CI 1.69-3.24) and for CAG plus PCI was 1.98 (95% CI 1.26-3.09). The aOR for CPC 1/2 with CAG alone was 6.89 (95% CI 3.99-11.91) and for CAG plus PCI was 2.95 (95% CI 1.59-5.47). After propensity matching, CAG was associated with an aOR for survival of 2.10 (95% CI 1.30-3.55) and for CPC 1/2 it was 5.06 (95% CI 2.29-11.19).In OHCA without STE, CAG was strongly and independently associated with survival regardless of whether PCI was performed. The association between CAG and positive outcomes remained after propensity matching.

The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers. Biopsies were performed at baseline, 5 minutes, 1, 5, and 24 hours after SSL irradiation. Within the PI3K/Akt pathway, we found activation of Akt (serine 473) to be significantly increased at 5 hours while mTOR (serine 2448) was strongly activated early and was sustained over 24 hours after SSL. Downstream, we observed a marked and sustained increase in phospho-S6 (serine 235/S236), whereas phospho-4E-BP1 (threonines 37/46) was increased only at 24 hours. Within the MAPK pathway, SSL-induced expression of phospho-p38 (threonine 180/tyrosine 182) peaked at 1 to 5 hours. ERK 1/2 was observed to be immediate and sustained after SSL irradiation. Phosphorylation of histone H3 (serine 10), a core structural protein of the nucleosome, peaked at 5 hours after SSL irradiation. The expression of both p53 and COX-2 was increased at 5 hours and was maximal at 24 hours after SSL irradiation. Apoptosis was significantly increased at 24 hours as expected and indicative of a sunburn-type response to SSL. Understanding the timing of key protein expression changes in response to SSL will aid in development of mechanistic-based approaches for the prevention and control of skin cancers. Cancer Prev Res; 8(8); 720–8. ©2015 AACR.

Supplemental Digital Content is Available in the Text., Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use.

We consider the situation of estimating the marginal survival distribution from censored data subject to dependent censoring using auxiliary variables. We had previously developed a nonparametric multiple imputation approach. The method used two working proportional hazards (PH) models, one for the event times and the other for the censoring times, to define a nearest neighbor imputing risk set. This risk set was then used to impute failure times for censored observations. Here, we adapt the method to the situation where the event and censoring times follow accelerated failure time models and propose to use the Buckley-James estimator as the two working models. Besides studying the performances of the proposed method, we also compare the proposed method with two popular methods for handling dependent censoring through the use of auxiliary variables, inverse probability of censoring weighted and parametric multiple imputation methods, to shed light on the use of them. In a simulation study with time-independent auxiliary variables, we show that all approaches can reduce bias due to dependent censoring. The proposed method is robust to misspecification of either one of the two working models and their link function. This indicates that a working proportional hazards model is preferred because it is more cumbersome to fit an accelerated failure time model. In contrast, the inverse probability of censoring weighted method is not robust to misspecification of the link function of the censoring time model. The parametric imputation methods rely on the specification of the event time model. The approaches are applied to a prostate cancer dataset.

Objectives Tenofovir disoproxol fumarate (TDF) is increasingly used in HAART regimens of pregnant women, but limited data exist on pregnancy pharmacokinetics of chronically-dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum.

Cerium oxide-doped ZnO sorbents were prepared by microwave calcination and conventional heating, respectively. The results show that microwave heating results in much better performance of the sorbents due to microwave effects on the structure of sorbents. XRD, XPS, N2 adsorption and SEM were used to characterize the structure of sorbents calcinated in two ways. The data indicate that microwave irradiation leads to better pore structure and smaller crystallite size of ZnO, which favors the dispersion of active components and the increase of contact area between ZnO and H2S. Microwave heating also results in greater outer layer electron density of surface atoms (Zn and O) and higher content of surface elements including Zn and O, which is favorable for the adsorption of acidic H2S and the reaction of H2S with ZnO on the surface of sorbents.

Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting. Cancer Prev Res; 8(1); 86–93. ©2014 AACR.

Author(s): Aweeka, FT; Hu, C; Huang, L; Best, BM; Stek, A; Lizak, P; Burchett, SK; Read, JS; Watts, H; Mirochnick, M; Capparelli, EV; International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team | Abstract: ObjectivesPregnancy results in physiological changes altering the pharmacokinetics of drugs metabolized by cytochrome P450 3A4 (CYP3A4). The urinary ratio of 6-β hydroxycortisol to cortisol (6βHF : F) is a marker of CYP3A4 induction. We sought to evaluate its change in antiretroviral (ARV)-treated HIV-1-infected women and to relate this change to ARV pharmacokinetics.MethodsWomen receiving various ARVs had pharmacokinetic evaluations during the third trimester of pregnancy (g30 weeks) and postpartum with determination of 6βHF : F carried out on the same days. The Wilcoxon signed rank test was used to compare the ratio antepartum to postpartum. The relationship between the change in ratio and the change in pharmacokinetics was analysed using Kendall's tau.Results6βHF : F ratios were available for 107 women antepartum, with 54 having postpartum values. The ratio was higher antepartum (P=0.033) (median comparison 1.35; 95% confidence interval 1.01, 1.81). For 71 women taking a protease inhibitor (PI), the antepartum vs. postpartum 6βHF : F comparison was marginally significant (P=0.058). When the change in the 6βHF : F ratio was related to the change in the dose-adjusted ARV area under the plasma concentration vs. time curve (AUC) between antepartum and postpartum, the 35 subjects in the lopinavir/ritonavir (LPV/r) arms demonstrated an inverse relationship (P=0.125), albeit this correlation did not reach statistical significance.ConclusionsA 35% increase in the urinary 6βHF : F ratio was measured during late pregnancy compared with postpartum, indicating that CYP3A induction occurs during pregnancy. The trend towards an inverse relationship between the change in the 6βHF : F ratio and the change in the LPV AUC antepartum vs. postpartum suggests that CYP3A induction may be one mechanism behind altered LPV exposure during pregnancy.

Background Emergency 9‐1‐1 callers use a wide range of terms to describe abnormal breathing in persons with out‐of‐hospital cardiac arrest ( OHCA ). These breathing descriptors can obstruct the telephone cardiopulmonary resuscitation ( CPR ) process. Methods and Results We conducted an observational study of emergency call audio recordings linked to confirmed OHCA s in a statewide Utstein‐style database. Breathing descriptors fell into 1 of 8 groups (eg, gasping, snoring). We divided the study population into groups with and without descriptors for abnormal breathing to investigate the impact of these descriptors on patient outcomes and telephone CPR process. Callers used descriptors in 459 of 2411 cases (19.0%) between October 1, 2010, and December 31, 2014. Survival outcome was better when the caller used a breathing descriptor (19.6% versus 8.8%, P OHCA recognition, CPR instruction, and telephone CPR were lower than when callers did not use a breathing descriptor (79.7% versus 93.0%, P P =0.0078; and 60.2% versus 66.9%, P =0.0123, respectively). The time interval between call receipt and OHCA recognition was longer when the caller used a breathing descriptor (118.5 versus 73.5 seconds, P Conclusions Descriptors of abnormal breathing are associated with improved outcomes but also with delays in the identification of OHCA . Familiarizing telecommunicators with these descriptors may improve the telephone CPR process including OHCA recognition for patients with increased probability of survival.