A large-format streak tube for compressed ultrafast photography.

Streak cameras are powerful imaging instruments for studying ultrafast dynamics with the temporal resolution ranging from picosecond to attosecond. However, the confined detection area limits the information capacity of streak cameras, preventing them from fulfilling their potential in lidar, compressed ultrafast photography, etc. Here, we designed and manufactured a large-format streak tube with a large-size round-aperture gate, a spherical cathode, and a spherical screen, leading to an expanded detection area and a high spatial resolution. The simulation results show that the physical temporal resolution of the streak tube is better than 45 ps and the spatial resolutions are higher than 14 lp/mm in the whole area of 24 × 28 mm2 on the cathode. The experiments demonstrate the streak tube's application potential in weak light imaging benefiting from the imaging magnification of 0.79, a photocathode radiance sensitivity of 37 mA/W, a radiant emitting gain of 11.6 at the wavelength of 500 nm, and a dynamic range higher than 512:1. Most importantly, in the photocathode area of Φ35 mm, the static spatial resolutions at the center and the edge along the slit (R = 16 mm) reach 32 and 28 lp/mm, respectively, and are higher than 10 lp/mm in the whole area of 24 × 28 mm2 on the cathode, allowing for a considerable capacity for spatial information.

ERINS: Novel Sequence Insertion Detection by Constructing an Extended Reference.

Next generation sequencing technology has led to the development of methods for the detection of novel sequence insertions (nsINS). Multiple signatures from short reads are usually extracted to improve nsINS detection performance. However, characterization of nsINSs larger than the mean insert size is still challenging. This article presents a new method, ERINS, to detect nsINS contents and genotypes of full spectrum range size. It integrates the features of structural variations and mapping states of split reads to find nsINS breakpoints, and then adopts a left-most mapping strategy to infer nsINS content by iteratively extending the standard reference at each breakpoint. Finally, it realigns all reads to the extended reference and infers nsINS genotypes through statistical testing on read counts. We test and validate the performance of ERINS on simulation and real sequencing datasets. The simulation experimental results demonstrate that it outperforms several peer methods with respect to sensitivity and precision. The real data application indicates that ERINS obtains high consistent results with those of previously reported and detects nsINSs over 200 base pairs that many other methods fail. In conclusion, ERINS can be used as a supplement to existing tools and will become a routine approach for characterizing nsINSs.

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression.

Long intergenic nonprotein-coding RNA 00514 (LINC00514) is upregulated in papillary thyroid cancer and contributes to its aggressiveness. In this study, we thoroughly explored the expression profile, specific functions, and relevant molecular mechanism of LINC00514 in osteosarcoma (OS). Herein, LINC00514 was significantly upregulated in OS tissues and cells, and increased LINC00514 expression was closely correlated with tumor size, TNM stage, and distant metastasis. OS patients with high LINC00514 expression had shorter overall survival than those with low LINC00514 expression. LINC00514 interference inhibited OS cell proliferation, colony formation, migration, and invasion in vitro but promoted cell apoptosis and G0/G1 cell cycle arrest. LINC00514 downregulation hindered OS tumor growth in vivo. Mechanistically, LINC00514 functioned as a competing endogenous RNA by directly interacting with microRNA-708-5p (miR-708) and consequently increasing the expression of upregulator of cell proliferation (URGCP). Both miR-708 knockdown and URGCP restoration partially neutralized anticancer activities of LINC00514 silencing in OS cells. LINC00514 increases URGCP expression by acting as a competing endogenous RNA for miR-708, thus exerting oncogenic roles in OS progression. In conclusion, the LINC00514/miR-708/URGCP pathway may be a promising target for drug discovery in the future.

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study.

RATIONALE: Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective. OBJECTIVES: We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers. METHODS: Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers. MEASUREMENTS AND MAIN RESULTS: Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08-1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16-1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant. CONCLUSIONS: Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites.

Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study.

BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES: The goal of this study was to evaluate the association of digoxin with mortality in AF. METHODS: Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. RESULTS: Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. CONCLUSIONS: Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.

Facility-level analysis of PET scanning for staging among US veterans with non-small cell lung cancer.

BACKGROUND: PET scanning has been shown in randomized trials to reduce the frequency of surgery without cure among patients with potentially resectable non-small cell lung cancer (NSCLC). We examined whether more frequent use of PET scanning at the facility level improves survival among patients with NSCLC in real-world practice. METHODS: In this prospective cohort study of 622 US veterans with newly diagnosed NSCLC, we compared groups defined by the frequency of PET scan use measured at the facility level and categorized as low (<25%), medium (25%-60%), or high (>60%). RESULTS: The median age of the sample was 69 years. Ninety-eight percent were men, 36% were Hispanic or nonwhite, and 54% had moderate or severe comorbidities. At low-, medium-, and high-use facilities, PET scan was performed in 13%, 40%, and 72% of patients, respectively (P<.0001). Baseline characteristics were similar across groups, including clinical stage based on CT scanning. More frequent use of PET scanning was associated with more frequent invasive staging (P<.001) and nonsignificant improvements in downstaging (P=.13) and surgery without cure (P=.12). After a median of 352 days of follow-up, 22% of the sample was still alive, including 22% at low- and medium-use facilities and 20% at high-use facilities. After adjustment and compared with patients at low-use facilities, the hazard of death was greater for patients at high-use facilities (adjusted hazard ratio [HR], 1.35; 95% CI, 1.05-1.74) but not different for patients at medium-use facilities (adjusted HR, 1.14; 95% CI, 0.88-1.46). CONCLUSIONS: In this study of veterans with NSCLC, markedly greater use of PET scanning at the facility level was associated with more frequent use of invasive staging and possible improvements in downstaging and surgery without cure, but greater use of PET scanning was not associated with better survival.

Diagnostic utility of a novel leadless arrhythmia monitoring device.

Although extending the duration of ambulatory electrocardiographic monitoring beyond 24 to 48 hours can improve the detection of arrhythmias, lead-based (Holter) monitors might be limited by patient compliance and other factors. We, therefore, evaluated compliance, analyzable signal time, interval to arrhythmia detection, and diagnostic yield of the Zio Patch, a novel leadless, electrocardiographic monitoring device in 26,751 consecutive patients. The mean wear time was 7.6 ± 3.6 days, and the median analyzable time was 99% of the total wear time. Among the patients with detected arrhythmias (60.3% of all patients), 29.9% had their first arrhythmia and 51.1% had their first symptom-triggered arrhythmia occur after the initial 48-hour period. Compared with the first 48 hours of monitoring, the overall diagnostic yield was greater when data from the entire Zio Patch wear duration were included for any arrhythmia (62.2% vs 43.9%, p <0.0001) and for any symptomatic arrhythmia (9.7% vs 4.4%, p <0.0001). For paroxysmal atrial fibrillation (AF), the mean interval to the first detection of AF was inversely proportional to the total AF burden, with an increasing proportion occurring after 48 hours (11.2%, 10.5%, 20.8%, and 38.0% for an AF burden of 51% to 75%, 26% to 50%, 1% to 25%, and <1%, respectively). In conclusion, extended monitoring with the Zio Patch for ≤14 days is feasible, with high patient compliance, a high analyzable signal time, and an incremental diagnostic yield beyond 48 hours for all arrhythmia types. These findings could have significant implications for device selection, monitoring duration, and care pathways for arrhythmia evaluation and AF surveillance.

Receipt of cervical cancer screening in female veterans: impact of posttraumatic stress disorder and depression.

PURPOSE: We evaluated receipt of cervical cancer screening in a national sample of 34,213 women veterans using Veteran Health Administration facilities between 2003 and 2007 and diagnosed with 1) posttraumatic stress disorder (PTSD), or 2) depression, or 3) no psychiatric illness. METHODS: Our study featured a cross-sectional design in which logistic regression analyses compared receipt of recommended cervical cancer screening for all three diagnostic groups. RESULTS: Cervical cancer screening rates varied minimally by diagnostic group: 77% of women with PTSD versus 75% with depression versus 75% without psychiatric illness were screened during the study observation period (p < .001). However, primary care use was associated with differential odds of screening in women with versus without psychiatric illness (PTSD or depression), even after adjustment for age, income and physical comorbidities (Wald Chi-square (2): 126.59; p < .0001). Specifically, among low users of primary care services, women with PTSD or depression were more likely than those with no psychiatric diagnoses to receive screening. Among high users of primary care services, they were less likely to receive screening. CONCLUSION: Psychiatric illness (PTSD or depression) had little to no effect on receipt of cervical cancer screening. Our finding that high use of primary care services was not associated with comparable odds of screening in women with versus without psychiatric illness suggests that providers caring for women with PTSD or depression and high use of primary care services should be especially attentive to their preventive healthcare needs.

Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study.

BACKGROUND: Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF. METHODS: In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin. RESULTS: In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 ± 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001). CONCLUSION: In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

Disparities in lung cancer staging with positron emission tomography in the Cancer Care Outcomes Research and Surveillance (CanCORS) study.

INTRODUCTION: Disparities in treatment exist for nonwhite and Hispanic patients with non-small cell lung cancer, but little is known about disparities in the use of staging tests or their underlying causes. METHODS: Prospective, observational cohort study of 3638 patients with newly diagnosed non-small cell lung cancer from 4 large, geographically defined regions, 5 integrated health care systems, and 13 VA health care facilities. RESULTS: Median age was 69 years, 62% were men, 26% were Hispanic or nonwhite, 68% graduated high school, 50% had private insurance, and 41% received care in the VA or another integrated health care system. After adjustment, positron emission tomography (PET) use was 13% lower among nonwhites and Hispanics than non-Hispanic whites (risk ratio [RR] 0.87, 95% confidence interval [CI] 0.77-0.97), 13% lower among those with Medicare than those with private insurance (RR 0.87, 95% CI 0.76-0.99), and 24% lower among those with an elementary school education than those with a graduate degree (RR 0.76, 95% CI 0.57-0.98). Disparate use of PET was not observed among patients who received care in an integrated health care setting, but the association between race/ethnicity and PET use was similar in magnitude across all other subgroups. Further analysis showed that income, education, insurance, and health care setting do not explain the association between race/ethnicity and PET use. CONCLUSIONS: Hispanics and nonwhites with non-small cell lung cancer are less likely to receive PET imaging. This finding is consistent across subgroups and not explained by differences in income, education, or insurance coverage.

Does sex influence immunization status for influenza and pneumonia in older veterans?

OBJECTIVES: To compare the prevalence of influenza and pneumococcal immunization rates according to sex in a national sample of older veterans in the Department of Veterans Affairs (VA) healthcare system. DESIGN: Retrospective, cross-sectional. SETTING: VA healthcare system. PARTICIPANTS: Current VA healthcare system users aged 65 and older eligible for immunization in fiscal years 2001 to 2003 (N=48,424 patient records). MEASUREMENTS: Generalized estimating equations were performed to analyze combined chart review and administrative data to determine effect of sex on receipt of influenza and pneumococcal immunizations. RESULTS: Unadjusted immunization rates were higher for men than women for influenza (73% vs 69%) and pneumococcal (87% vs 83%) vaccine. Adjusting for demographics, clinical comorbidities, use, and region, women had significantly lower odds of influenza (odds ratio (OR)=0.85, 95% confidence interval (CI=0.79-0.92) and pneumococcal (OR=0.77, 95% CI=0.71-0.84) immunization. CONCLUSION: Older female veterans have lower rates of immunization than older male veterans in VA settings. Although VA remains above community levels for immunization, older female veterans will benefit from targeted efforts to increase immunization prevalence.

Cardiovascular disease and metabolic risk factors in male patients with schizophrenia, schizoaffective disorder, and bipolar disorder.

The authors determined whether diagnoses of cardiovascular disease (CVD) and CVD-related conditions differed by psychiatric diagnosis among male Veterans Administration patients from the mid-Atlantic region. Among 7,529 patients (mean age: 54.5 years), the prevalence of diagnoses ranged from 3.6% (stroke) to 35.4% (hypertension). Compared with schizophrenia patients, those with bipolar disorder were 19% more likely to have diabetes, 44% more likely to have coronary artery disease, and 18% more likely to have dyslipidemia, after adjustment. Clinical suspicion for CVD-related conditions, as well as risk-modification strategies, in patients with serious mental illness should incorporate differences in prevalence across specific psychiatric diagnoses.

Quality of care for substance use disorders in patients with serious mental illness.

We assessed the quality of care for substance use disorders (SUDs) among 8,083 patients diagnosed with serious mental illness from the VA mid-Atlantic region. Using data from the National Patient Care Database (2001-2002), we assessed the percentage of patients receiving a diagnosis of SUD, percentage beginning SUD treatment 14 days or earlier after diagnosis, and percentage receiving continued SUD care 30 days or less. Overall, 1,559 (19.3%) were diagnosed with an SUD. Of the 1,559, 966 (62.0%) initiated treatment and 847 (54.3%) received continued care. Although patients diagnosed with bipolar disorder were more likely to receive a diagnosis of SUD than those diagnosed with schizophrenia or schizoaffective disorder (22.7%, 18.9%, and 17.7%, respectively; chi(2) = 26.02, df = 2, p < .001), they were less likely to initiate (49.1%, 70.7%, and 68.6%, respectively; chi(2) = 59.29, df = 2, p < .001) or continue treatment (39.9%, 63.2%, and 62.2%, respectively; chi(2) = 72.25, df = 2, p <. 001). Greater efforts are needed to diagnose and treat SUDs in patients with serious mental illness, particularly for those with bipolar disorder.