Purpose We assessed the relationship of surgical margins across different surgical approaches to partial nephrectomy in patients with clinical T1a renal cell carcinoma in a population based cohort. ...Materials and Methods We used NCDB (National Cancer Database) to identify all patients who underwent partial nephrectomy for clinical T1a renal cell carcinoma (tumor size less than 4 cm) from 2010 to 2011. The primary outcome was surgical margin status in patients treated with partial nephrectomy by the open, laparoscopic or robotic approach. Multivariable logistic regression analysis was done to identify patient, hospital and surgical factors associated with positive surgical margins. Results Partial nephrectomy was done in 11,587 patients, including open, laparoscopic and robotic nephrectomy in 5,094 (44%), 1,681 (14%) and 4,812 (42%), respectively. Mean ± SD age was 56 ± 12 years. Overall 806 patients (7%) had positive surgical margins. The positive surgical margin prevalence was 4.9%, 8.1% and 8.7% for the open, laparoscopic and robotic approaches, respectively (p <0.001). Laparoscopic and robotic partial nephrectomy had a higher adjusted OR for positive surgical margins (OR 1.81 and 1.79, respectively, each p <0.001) than open nephrectomy. When stratified by hospital type, differences in positive surgical margin rates remained, such that patients treated at academic medical centers who underwent laparoscopic and robotic partial nephrectomy had a higher adjusted OR (1.38, p = 0.074 and 1.73, p <0.001, respectively) than patients treated with open partial nephrectomy. Conclusions Laparoscopic and robotic partial nephrectomy is associated with higher positive surgical margin rates compared to open partial nephrectomy for clinical T1a renal cell carcinoma. The effect of margin status on long-term oncologic outcomes in this context remains to be determined.
In 2015, we founded Pedi Lyme Net, a pediatric Lyme disease research network comprising 8 emergency departments in the United States. Of 2,497 children evaluated at 1 of these sites for Lyme disease, ...515 (20.6%) were infected. This network is a unique resource for evaluating new approaches for diagnosing Lyme disease in children.
Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine ...aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34-97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00-1.02)), male (OR 1.37 (95% CI 1.17-1.59)), have ALT elevation (OR 3.21 (95% CI 2.59-3.99)), diabetes (OR 3.39 (95% CI 2.61-4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12-0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05-1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59-2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7-0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.
We assessed the effectiveness of South Africa's Firearm Control Act (FCA), passed in 2000, on firearm homicide rates compared with rates of nonfirearm homicide across 5 South African cities from 2001 ...to 2005.
We conducted a retrospective population-based study of 37 067 firearm and nonfirearm homicide cases. Generalized linear models helped estimate and compare time trends of firearm and nonfirearm homicides, adjusting for age, sex, race, day of week, city, year of death, and population size.
There was a statistically significant decreasing trend regarding firearm homicides from 2001, with an adjusted year-on-year homicide rate ratio of 0.864 (95% confidence interval CI = 0.848, 0.880), representing a decrease of 13.6% per annum. The year-on-year decrease in nonfirearm homicide rates was also significant, but considerably lower at 0.976 (95% CI = 0.954, 0.997). Results suggest that 4585 (95% CI = 4427, 4723) lives were saved across 5 cities from 2001 to 2005 because of the FCA.
Strength, timing and consistent decline suggest stricter gun control mediated by the FCA accounted for a significant decrease in homicide overall, and firearm homicide in particular, during the study period.
A field-portable device for logging PM
2.5
mass concentration data has been developed. The device combines the Arduino microprocessor with an SD card, a Sharp DN7C3CA006 optical dust monitor, and ...10,000-mAh battery. The dust sensor uses a virtual impactor to size select particles <2.5 microns prior to illuminating the selected fraction with an LED. The LED is triggered by a circuit controlled with the Arduino. Nephelometric detection at 120° referenced to incidence is used. The voltage signal reported by the dust sensor is converted to PM
2.5
mass through calibration onboard the Arduino. Data points can be saved to the SD card as rapidly as 0.3 s, although averaging signals over 60 s produced more optimal detection limits. For a 60 s average, the PM
2.5
mass limit of detection was 9 µg m
−3
, indicating that the sensor will be useful for monitoring human exposure to fine particles. Portable exposure monitoring has been demonstrated with the sensing platform as several individuals carried the device with them during daily activities in Lubbock, TX and Atlanta, GA. For this group of test subjects, values of PM
2.5
exposure varied from 0 to 1000 µg m
−3
during the sampling periods. It was observed that, by far, the highest levels of PM
2.5
occur during periods of cooking, or being near cooking operations. Other periods of high PM
2.5
occurred during ground transportation, use of personal care products, vacuuming, and visiting restrooms. When hourly personal exposure data were correlated with hourly average PM
2.5
for outdoor air for the Atlanta data set, a very weak correlation was found (R
2
= 0.026). Only two out of eight sampling periods did the personal monitoring estimate of exposure agree with that predicted by outdoor monitoring to within 15%. Personal exposure was often affected by circumstantial, short-term, high exposure events that are difficult to model or predict effectively. The short-term exposure events generally cause true exposure to be higher than that predicted by using outdoor ambient PM
2.5
to generate estimates. This finding complicates interpretation of epidemiological studies that find links between ambient outdoor PM
2.5
levels and human health, while it buttresses the case for using personal ambient monitors.
The data presented within this manuscript reports the results of a 20-question opinion survey concerning popular beliefs regarding the causes of and possible mitigation of climate change. The results ...and opinions from 746 survey respondents are presented. The data reflects certain misconceptions of climate change, and is useful for investigators to begin forming opinions of the public's knowledge regarding the potentially inflammatory topics of climate change, greenhouse gases, and geo-engineering.
Cyclin-dependent kinases (CDK), and their regulatory cyclin partners, play a central role in eukaryotic cell growth, division, and death. This key role in cell cycle progression, as well as their ...deregulation in several human cancers, makes them attractive therapeutic targets in oncology. A series of CDK inhibitors was developed using Astex's fragment-based medicinal chemistry approach, linked to high-throughput X-ray crystallography. A compound from this series, designated AT7519, is currently in early-phase clinical development. We describe here the biological characterization of AT7519, a potent inhibitor of several CDK family members. AT7519 showed potent antiproliferative activity (40-940 nmol/L) in a panel of human tumor cell lines, and the mechanism of action was shown here to be consistent with the inhibition of CDK1 and CDK2 in solid tumor cell lines. AT7519 caused cell cycle arrest followed by apoptosis in human tumor cells and inhibited tumor growth in human tumor xenograft models. Tumor regression was observed following twice daily dosing of AT7519 in the HCT116 and HT29 colon cancer xenograft models. We show that these biological effects are linked to inhibition of CDKs in vivo and that AT7519 induces tumor cell apoptosis in these xenograft models. AT7519 has an attractive biological profile for development as a clinical candidate, and the tolerability and efficacy in animal models compare favorably with other CDK inhibitors in clinical development. Studies described here formed the biological rationale for investigating the potential therapeutic benefit of AT7519 in cancer patients.
Electronic capacitors were constructed via hand-printing on paper using pencil graphite. Graphite traces were used to draw conductive connections and capacitor plates on opposing sides of a sheet of ...standard notebook paper. The paper served as the dielectric separating the plates. Capacitance of the devices was generally < 1000 pF and scaled with surface area of the plate electrodes. By combining a pencil-drawn capacitor with an additional resistive pencil trace, an RC low-pass filter was demonstrated. Further utility of the pencil-on-paper devices was demonstrated through description of a capacitive force transducer and reversible chemical sensing. The latter was achieved for water vapor when the hygroscopic cellulose matrix of the paper capacitor’s dielectric adsorbed water. The construction and demonstration of pencil-on-paper capacitive elements broadens the scope of paper-based electronic circuits while allowing new opportunities in the rapidly expanding field of paper-based sensors.
A syringe-based, electronic fluid dispenser is described. The device mechanically connects a syringe plunger to a linear slide potentiometer. As the syringe plunger moves, the electrical resistance ...between terminals of the potentiometer varies. Application and subsequent measurement of a DC voltage between the potentiometer pins is used to track the syringe plunger position and meter the volume dispensed. The syringe’s plunger is actuated manually by the device’s user. The dispensing device offers volumetric accuracy of better than 1% when the dispensed volumes were >10 mL. The device has been used for a traditional acid–base titration experiment and produced quantitative results indistinguishable from the conventional approach using a buret. The device is inexpensive, easy for students to understand, and simple to construct.
Global climate, atmospheric chemistry, and air quality are affected by tropospheric particulate matter. Recent measurements suggest organic compounds present in this haze comprise roughly half of ...total aerosol fine mass concentration globally. Unlike the well-constrained processes which result in formation of nitrate or sulfate aerosol, the oxidation of volatile organics in the atmosphere can lead to thousands of stable compounds in the aerosol phase. Development of a tractable framework to consider the chemical and physical evolution of the organic aerosol is crucial for modeling its effect on global climate. Here we show coupling a 3-dimensional coordinate system defined by the molecular descriptors of molecular weight, heteroatom mass, and double bond equivalents (D.B.E.) with high-resolution molecular mass spectrometry is a powerful approach for describing key properties of the organic aerosol. The scheme is conceptually simple, yet maintains sufficient complexity to be compatible with quantitative structure–property relationships (QSPRs) used to predict chemical and physical properties that govern aerosol behavior. From available data, both ambient organic aerosol and laboratory generated organic aerosol frequently occupy the region characterized by <10 D.B.E. <600 M.W. and <200 heteroatom mass. A QSPR analysis conducted illustrates spatial trends within the 3D space for volatility and Henry's law constants for 31,000 organic compounds considered.
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