West Virginia University Hospitals

The EACVI/ASE/Industry Task Force to standardize deformation imaging prepared this consensus document to standardize definitions and techniques for using two-dimensional (2D) speckle tracking echocardiography (STE) to assess left atrial, right ventricular, and right atrial myocardial deformation. This document is intended for both the technical engineering community and the clinical community at large to provide guidance on selecting the functional parameters to measure and how to measure them using 2D STE.This document aims to represent a significant step forward in the collaboration between the scientific societies and the industry since technical specifications of the software packages designed to post-process echocardiographic datasets have been agreed and shared before their actual development. Hopefully, this will lead to more clinically oriented software packages which will be better tailored to clinical needs and will allow industry to save time and resources in their development.

Circadian rhythms are internal manifestations of the solar day that permit adaptations to predictable environmental temporal changes. These ~24-h rhythms are controlled by molecular clockworks within the brain that are reset daily to precisely 24 h by exposure to the light-dark cycle. Information from the master clock in the mammalian hypothalamus conveys temporal information to the entire body via humoral and neural communication. A bidirectional relationship exists between mood disorders and circadian rhythms. Mood disorders are often associated with disrupted circadian clock-controlled responses, such as sleep and cortisol secretion, whereas disruption of circadian rhythms via jet lag, night-shift work, or exposure to artificial light at night, can precipitate or exacerbate affective symptoms in susceptible individuals. Evidence suggests strong associations between circadian rhythms and mental health, but only recently have studies begun to discover the direct interactions between the circadian system and mood regulation. This review provides an overview of disrupted circadian rhythms and the relationship to behavioral health and psychiatry. The focus of this review is delineating the role of disruption of circadian rhythms on mood disorders using human night shift studies, as well as jet lag studies to identify links. We also review animal models of disrupted circadian rhythms on affective responses. Lastly, we propose low-cost behavioral and lifestyle changes to improve circadian rhythms and presumably behavioral health.

Biomimetic nanofibrous scaffolds mimicking important features of the native extracellular matrix provide a promising strategy to restore functions or achieve favorable responses for tissue regeneration. This review provides a brief overview of current state-of-the-art research designing and using biomimetic electrospun nanofibers as scaffolds for tissue engineering. It begins with a brief introduction of electrospinning and nanofibers, with a focus on issues related to the biomimetic design aspects. The review next focuses on several typical biomimetic nanofibrous structures (e.g. aligned, aligned to random, spiral, tubular, and sheath membrane) that have great potential for tissue engineering scaffolds, and describes their fabrication, advantages, and applications in tissue engineering. The review concludes with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers.

The authors investigated whether neighborhood socioeconomic characteristics are associated with coronary heart disease prevalence and risk factors, whether these associations persist after adjustment for individual-level social class indicators, and whether the effects of individual-level indicators vary across neighborhoods. The study sample consisted of 12,601 persons in four US communities (Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, Minnesota; and Jackson, Mississippi) participating in the baseline examination of the Atherosclerosis Risk in Communities Study (1987-1989). Neighborhood characteristics were obtained from 1990 US Census block-group measures. Multilevel models were used to estimate associations with neighborhood variables after adjustment for individual-level indicators of social class. Living in deprived neighborhoods was associated with increased prevalence of coronary heart disease and increased levels of risk factors, with associations generally persisting after adjustment for individual-level variables. Inconsistent associations were documented for serum cholesterol and disease prevalence in African-American men. For Jackson African-American men living in poor neighborhoods, coronary heart disease prevalence decreased as neighborhood characteristics worsened. Additionally, in African-American men from Jackson, low social class was associated with increased serum cholesterol in "richer" neighborhoods but decreased serum cholesterol in "poorer" neighborhoods. Neighborhood environments may be one of the pathways through which social structure shapes coronary heart disease risk.

This study focused on the relationship between percentage of vocabulary known in a text and level of comprehension of the same text. Earlier studies have estimated the percentage of vocabulary necessary for second language learners to understand written texts as being between 95% ( Laufer, 1989 ) and 98% ( Hu & Nation, 2000 ). In this study, 661 participants from 8 countries completed a vocabulary measure based on words drawn from 2 texts, read the texts, and then completed a reading comprehension test for each text. The results revealed a relatively linear relationship between the percentage of vocabulary known and the degree of reading comprehension. There was no indication of a vocabulary “threshold,” where comprehension increased dramatically at a particular percentage of vocabulary knowledge. Results suggest that the 98% estimate is a more reasonable coverage target for readers of academic texts.

Primary dysmenorrhea is painful menstrual cramps without any evident pathology to account for them, and it occurs in up to 50% of menstruating females and causes significant disruption in quality of life and absenteeism. Current understanding implicates an excessive or imbalanced amount of prostanoids and possibly eicosanoids released from the endometrium during menstruation. The uterus is induced to contract frequently and dysrhythmically, with increased basal tone and increased active pressure. Uterine hypercontractility, reduced uterine blood flow, and increased peripheral nerve hypersensitivity induce pain. Diagnosis rests on a good history with negative pelvic evaluation findings. Evidence-based data support the efficacy of cyclooxygenase inhibitors, such as ibuprofen, naproxen sodium, and ketoprofen, and estrogen-progestin oral contraceptive pills (OCPs). Cyclooxygenase inhibitors reduce the amount of menstrual prostanoids released, with concomitant reduction in uterine hypercontractility, while OCPs inhibit endometrial development and decrease menstrual prostanoids. An algorithm is provided for a simple approach to the management of primary dysmenorrhea.

Artificial intelligence (AI) broadly refers to analytical algorithms that iteratively learn from data, allowing computers to find hidden insights without being explicitly programmed where to look. These include a family of operations encompassing several terms like machine learning, cognitive learning, deep learning and reinforcement learning-based methods that can be used to integrate and interpret complex biomedical and healthcare data in scenarios where traditional statistical methods may not be able to perform. In this review article, we discuss the basics of machine learning algorithms and what potential data sources exist; evaluate the need for machine learning; and examine the potential limitations and challenges of implementing machine in the context of cardiovascular medicine. The most promising avenues for AI in medicine are the development of automated risk prediction algorithms which can be used to guide clinical care; use of unsupervised learning techniques to more precisely phenotype complex disease; and the implementation of reinforcement learning algorithms to intelligently augment healthcare providers. The utility of a machine learning-based predictive model will depend on factors including data heterogeneity, data depth, data breadth, nature of modelling task, choice of machine learning and feature selection algorithms, and orthogonal evidence. A critical understanding of the strength and limitations of various methods and tasks amenable to machine learning is vital. By leveraging the growing corpus of big data in medicine, we detail pathways by which machine learning may facilitate optimal development of patient-specific models for improving diagnoses, intervention and outcome in cardiovascular medicine.

BACKGROUND: Nurse job dissatisfaction has been the primary predictor of intent to leave; however, although many predictors of job satisfaction have been identified, little is known about the influence of variable nurse attitudes, such as psychological empowerment and hardiness, on job satisfaction. OBJECTIVE: The purpose of this study was to investigate the relative influence of nurse attitudes, context of care, and structure of care on job satisfaction and intent to leave. METHODS: A nonexperimental, predictive design evaluated these relationships in a nonrandom sample of 90 registered staff nurses using instruments with known psychometric properties. RESULTS: The major predictor of intent to leave was job dissatisfaction, and the major predictor of job satisfaction was psychological empowerment. Predictors of psychological empowerment were hardiness, transformational leadership style, nurse/physician collaboration, and group cohesion. CONCLUSIONS: Results supported the influence of nurse attitude on job satisfaction relative to other contributing factors.

BACKGROUND: Overweight and obesity is a major public health concern that includes associations with the development of cardiovascular disease (CVD) risk factors during childhood and adolescence as well as premature mortality in adults. Despite the high prevalence of childhood and adolescent obesity as well as adult CVD, individual studies as well as previous systematic reviews examining the relationship between childhood obesity and adult CVD have yielded conflicting results. The purpose of this study was to use the aggregate data meta-analytic approach to address this gap. METHODS: Studies were included if they met the following criteria: (1) longitudinal and cohort studies (including case-cohort), (2) childhood exposure and adult outcomes collected on the same individual over time, (3) childhood obesity, as defined by the original study authors, (4) English-language articles, (5) studies published up to June, 2015, (6) one or more of the following CVD risk factors [systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), non-high-density lipoprotein cholesterol (non-HDL), and triglycerides (TG)], (7) outcome(s) not self-reported, and (8) exposure measurements (child's adiposity) assessed by health professionals, trained investigators, or self-reported. Studies were retrieved by searching three electronic databases as well as citation tracking. Fisher's r to z score was calculated for each study for each outcome. Pooled effect sizes were calculated using random-effects models while risk of bias was assessed using the STROBE instrument. In order to try and identify sources of heterogeneity, random-effects meta-regression was also performed. RESULTS: Of the 4840 citations reviewed, a total of 23 studies were included in the systematic review and 21 in the meta-analysis. The findings suggested that childhood obesity is significantly and positively associated with adult SBP (Zr = 0.11; 95% CI: 0.07, 0.14), DBP (Zr = 0.11; 95% CI: 0.07, 0.14), and TG (Zr =0.08; 95% CI: 0.03, 0.13), and significantly and inversely associated with adult HDL (Zr = -0.06; 95% CI: -0.10, -0.02). For those studies that adjusted for adult body mass index (BMI), associations were reversed, suggesting that adult BMI may be a potential mediator. Nine studies had more than 33% of items that placed them at an increased risk for bias. CONCLUSIONS: The results of this study suggest that childhood obesity may be a risk factor for selected adult CVD risk factors. However, a need exists for additional, higher-quality studies that include, but are not limited to, both unadjusted and adjusted measures such as BMI before any definitive conclusions can be reached. SYSTEMATIC REVIEW AND META-ANALYSIS: PROSPERO 2015: CRD42015019763 .

Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial. Noninvasive diagnostic methods include serum markers like alkaline phosphatase and a growing variety of imaging techniques including X-ray, computed tomography, magnetic resonance imaging, and positron emission as well as combinations thereof. Still, biopsy and microscopic examination are required to confirm the diagnosis and carry additional prognostic implications such as subtype classification and histological response to neoadjuvant chemotherapy. The current standard of care combines surgical and chemotherapeutic techniques, with a multitude of experimental biologics and small molecules currently in development and some in clinical trial phases. In this review, in addition to summarizing the current understanding of OS etiology, diagnostic methods, and the current standard of care, our group describes various experimental therapeutics and provides evidence to encourage a potential paradigm shift toward the introduction of immunomodulation, which may offer a more comprehensive approach to battling cancer pleomorphism.

After a recent series of rapid and exciting developments, the long search for the Majorana fermion-the elusive quantum entity at the border between particles and antiparticles-has produced the first positive experimental results, but is not over yet. Originally proposed by E Majorana in the context of particle physics, Majorana fermions have a condensed matter analogue in the zero-energy bound states emerging in topological superconductors. A promising route to engineering topological superconductors capable of hosting Majorana zero modes consists of proximity coupling semiconductor thin films or nanowires with strong spin-orbit interaction to conventional s-wave superconductors in the presence of an external Zeeman field. The Majorana zero mode is predicted to emerge above a certain critical Zeeman field as a zero-energy state localized near the order parameter defects, namely, vortices for thin films and wire ends for the nanowire. These Majorana bound states are expected to manifest non-Abelian quantum statistics, which makes them ideal building blocks for fault-tolerant topological quantum computation. This review provides an update on the current status of the search for Majorana fermions in semiconductor nanowires by focusing on the recent developments, in particular the period following the first reports of experimental signatures consistent with the realization of Majorana bound states in semiconductor nanowire-superconductor hybrid structures. We start with a discussion of the fundamental aspects of the subject, followed by considerations on the realistic modeling, which is a critical bridge between theoretical predictions based on idealized conditions and the real world, as probed experimentally. The last part is dedicated to a few intriguing issues that were brought to the fore by the recent encouraging experimental advances.

Where does the sparsity in image signals come from? Local and nonlocal image models have supplied complementary views toward the regularity in natural images - the former attempts to construct or learn a dictionary of basis functions that promotes the sparsity; while the latter connects the sparsity with the self-similarity of the image source by clustering. In this paper, we present a variational framework for unifying the above two views and propose a new denoising algorithm built upon clustering-based sparse representation (CSR). Inspired by the success of l1-optimization, we have formulated a double-header l1-optimization problem where the regularization involves both dictionary learning and structural structuring. A surrogate-function based iterative shrinkage solution has been developed to solve the double-header l1-optimization problem and a probabilistic interpretation of CSR model is also included. Our experimental results have shown convincing improvements over state-of-the-art denoising technique BM3D on the class of regular texture images. The PSNR performance of CSR denoising is at least comparable and often superior to other competing schemes including BM3D on a collection of 12 generic natural images.

The bioavailability of nitric oxide (NO) in the human coronary circulation at rest and after acetylcholine (ACH)-induced vasodilation was investigated in 32 patients with angiographically normal coronary arteries. The effects of intracoronary L-NG monomethyl arginine (L-NMMA) were investigated at rest and after ACH, sodium nitroprusside, and adenosine. L-NMMA (64 mumol/min) increased resting coronary vascular resistance by 22% (P < 0.001), reduced distal epicardial coronary artery diameter by 12.6% (P < 0.001), and inhibited ACH-induced coronary epicardial and microvascular vasodilation. These effects were reversed with intracoronary L-arginine. L-NMMA did not inhibit dilation in response to sodium nitroprusside and adenosine. 23 patients were exposed to one or more coronary risk factors. The vasoconstrictor effect of L-NMMA on the epicardial and microvessels was greater in patients free of risk factors: Coronary vascular resistance was 36% higher in patients without risks, compared to 17% higher in patients with risks (P < 0.05). Both epicardial and microvascular dilator effects of ACH were greater in patients without risk factors, and the inhibition of these effects by L-NMMA was also greater in patients without risk factors. Thus: (a) NO contributes importantly to resting epicardial and coronary microvascular tone, (b) coronary vascular dilation in response to ACH is predominantly due to increased production of NO, and (c) despite the absence of angiographic evidence of atherosclerosis, exposure to coronary risk factors is associated with reduced resting and stimulated bioavailability of NO from the human coronary circulation.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P &lt;0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

To test the hypothesis that appropriate and timely neuromuscular control of limb motions plays an important role in the preservation of joint health, we kinematically and kinetically examined the behavior of the legs of young adult subjects at heel strike during natural walking. We compared a group of 18 volunteers, who, we presumed, were preosteoarthrotic because of mild, intermittent, activity-related knee joint pain, with 14 age-matched asymptomatic normal subjects. The two groups of subjects exhibited similar gait patterns with equivalent cadences, walking speeds, terminal stance phase knee flexion, maximum (peak) swing angular velocity, and overall shape of the vertical ground reaction. However, our instrumentation detected statistically significant differences between the two groups within a few milliseconds of heel strike. In the knee pain group, the heel hit the floor with a stronger impact in this brief interval. Just before heel strike, there was a faster downward velocity of the ankle with a larger angular velocity of the shank. The follow-through of the leg immediately after heel strike was more violent with larger peak axial and angular accelerations of the leg echoed by a more rapid rise of the ground reaction force. This sequence of events represents repetitive impulsive loading, which consistently provoked osteoarthrosis in animal experiments. We refer to this micro-incoordination of neuromuscular control not visible to the naked eye as "microklutziness."

CONTEXT: Many rural elders experience limited access to health care. The majority of what we know about this issue has been based upon quantitative studies, yet qualitative studies might offer additional insight into individual perceptions of health care access. PURPOSE: To examine what barriers rural elders report when accessing needed health care, including how they cope with the high cost of prescription medication. METHODS: During Spring 2001, thirteen 90-minute focus groups were conducted in 6 rural West Virginia communities. A total of 101 participants, aged 60 years and older, were asked several culminating questions about their perceptions of health care access. FINDINGS: Five categories of barriers to health care emerged from the discussions: transportation difficulties, limited health care supply, lack of quality health care, social isolation, and financial constraints. In addition, 6 diverse coping strategies for dealing with the cost of prescription medication were discussed. They included: reducing dosage or doing without, limiting other expenses, relying on family assistance, supplementing with alternative medicine, shopping around for cheapest prices, and using the Veteran's Administration. CONCLUSIONS: Overall, rural older adults encounter various barriers to accessing needed health care. Qualitative methodology allows rural elders to have a voice to expound on their experiences. Research can contribute valuable information to shape policy by providing a forum where older adults can express their concerns about the current health care delivery system.

Protein accumulation and aggregation with a concomitant loss of proteostasis often contribute to neurodegenerative diseases, and the ubiquitin-proteasome system plays a major role in protein degradation and proteostasis. Here, we show that three different proteins from Alzheimer's, Parkinson's, and Huntington's disease that misfold and oligomerize into a shared three-dimensional structure potently impair the proteasome. This study indicates that the shared conformation allows these oligomers to bind and inhibit the proteasome with low nanomolar affinity, impairing ubiquitin-dependent and ubiquitin-independent proteasome function in brain lysates. Detailed mechanistic analysis demonstrates that these oligomers inhibit the 20S proteasome through allosteric impairment of the substrate gate in the 20S core particle, preventing the 19S regulatory particle from injecting substrates into the degradation chamber. These results provide a novel molecular model for oligomer-driven impairment of proteasome function that is relevant to a variety of neurodegenerative diseases, irrespective of the specific misfolded protein that is involved.

OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients with typical cat-scratch disease. DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING: Large military medical center and its referring clinics. PATIENTS: Active duty military members and their dependents with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION: Study participants assigned by randomization to treatment with oral azithromycin or placebo for 5 days. OUTCOME MEASURES: Lymph node volume was calculated using three dimensional ultrasonography at entry and at weekly intervals. The ultrasonographer was blinded to the treatment groups. Endpoint evaluations were predetermined as time in days to 80% resolution of the initial total lymph node volume. RESULTS: Demographic and clinical data showed that the azithromycin and placebo treatment groups were comparable at entry although the placebo group tended to be older. Eighty percent decrease of initial lymph node volume was documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo-treated controls during the first 30 days of observation (P = 0.026). After 30 days there was no significant difference in rate or degree of resolution between the two groups. CONCLUSIONS: Treatment of patients with typical cat-scratch disease with oral azithromycin for five days affords significant clinical benefit as measured by total decrease in lymph node volume within the first month of treatment.

The ubiquitin proteasome system (UPS) degrades individual proteins in a highly regulated fashion and is responsible for the degradation of misfolded, damaged, or unneeded cellular proteins. During the past 20 years, investigators have established a critical role for the UPS in essentially every cellular process, including cell cycle progression, transcriptional regulation, genome integrity, apoptosis, immune responses, and neuronal plasticity. At the center of the UPS is the proteasome, a large and complex molecular machine containing a multicatalytic protease complex. When the efficiency of this proteostasis system is perturbed, misfolded and damaged protein aggregates can accumulate to toxic levels and cause neuronal dysfunction, which may underlie many neurodegenerative diseases. In addition, many cancers rely on robust proteasome activity for degrading tumor suppressors and cell cycle checkpoint inhibitors necessary for rapid cell division. Thus, proteasome inhibitors have proven clinically useful to treat some types of cancer, especially multiple myeloma. Numerous cellular processes rely on finely tuned proteasome function, making it a crucial target for future therapeutic intervention in many diseases, including neurodegenerative diseases, cystic fibrosis, atherosclerosis, autoimmune diseases, diabetes, and cancer. In this review, we discuss the structure and function of the proteasome, the mechanisms of action of different proteasome inhibitors, various techniques to evaluate proteasome function in vitro and in vivo, proteasome inhibitors in preclinical and clinical development, and the feasibility for pharmacological activation of the proteasome to potentially treat neurodegenerative disease.

BACKGROUND: Current information points to an association between diesel exhaust exposure and lung cancer and other mortality outcomes, but uncertainties remain. METHODS: We undertook a cohort mortality study of 12 315 workers exposed to diesel exhaust at eight US non-metal mining facilities. Historical measurements and surrogate exposure data, along with study industrial hygiene measurements, were used to derive retrospective quantitative estimates of respirable elemental carbon (REC) exposure for each worker. Standardized mortality ratios and internally adjusted Cox proportional hazard models were used to evaluate REC exposure-associated risk. Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death. RESULTS: Standardized mortality ratios for lung cancer (1.26, 95% confidence interval [CI] = 1.09 to 1.44), esophageal cancer (1.83, 95% CI = 1.16 to 2.75), and pneumoconiosis (12.20, 95% CI = 6.82 to 20.12) were elevated in the complete cohort compared with state-based mortality rates, but all-cause, bladder cancer, heart disease, and chronic obstructive pulmonary disease mortality were not. Differences in risk by worker location (ever-underground vs surface only) initially obscured a positive diesel exhaust exposure-response relationship with lung cancer in the complete cohort, although it became apparent after adjustment for worker location. The hazard ratios (HRs) for lung cancer mortality increased with increasing 15-year lagged cumulative REC exposure for ever-underground workers with 5 or more years of tenure to a maximum in the 640 to less than 1280 μg/m(3)-y category compared with the reference category (0 to <20 μg/m(3)-y; 30 deaths compared with eight deaths of the total of 93; HR = 5.01, 95% CI = 1.97 to 12.76) but declined at higher exposures. Average REC intensity hazard ratios rose to a plateau around 32 μg/m(3). Elevated hazard ratios and evidence of exposure-response were also seen for surface workers. The association between diesel exhaust exposure and lung cancer risk remained after inclusion of other work-related potentially confounding exposures in the models and were robust to alternative approaches to exposure derivation. CONCLUSIONS: The study findings provide further evidence that exposure to diesel exhaust increases risk of mortality from lung cancer and have important public health implications.