Vitamin D Levels in Patients with Colorectal Cancer and Matched Household Members.

BackgroundVitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients.MethodsThirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/- 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise.ResultsMedian serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P>0.05). Household members were more likely than CRC patients to be overweight and to exercise more.ConclusionsVitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted

Series Hybrid Vehicles and Optimized Hydrogen Engine Design

Lawrence Livermore, Sandia Livermore and Los Alamos National Laboratories have a joint project to develop an optimized hydrogen fueled engine for series hybrid automobiles. The major divisions of responsibility are: system analysis, engine design and kinetics modeling by LLNL; performance and emission testing, and friction reduction by SNL; computational fluid mechanics and combustion modeling by LANL. This project is a component of the Department of Energy, Office of Utility Technology, National Hydrogen Program. We report here on the progress on system analysis and preliminary engine testing. We have done system studies of series hybrid automobiles that approach the PNGV design goal of 34 km/liter (80 mpg), for 384 km (240 mi) and 608 km (380 mi) ranges. Our results indicate that such a vehicle appears feasible using an optimized hydrogen engine. The impact of various on-board storage options on fuel economy are evaluated. Experiments with an available engine at the Sandia Combustion Research Facility demonstrated NO{sub x} emissions of 10 to 20 ppm at an equivalence ratio of 0.4, rising to about 500 ppm at 0.5 equivalence ratio using neat hydrogen. Hybrid vehicle simulation studies indicate that exhaust NO{sub x} concentrations must be less than 180 ppm to meet the 0.2 g/mile California Air Resources Board ULEV or Federal Tier II emissions regulations. We have designed and fabricated a first generation optimized hydrogen engine head for use on an existing single cylinder Onan engine. This head currently features 14.8:1 compression ratio, dual ignition, water cooling, two valves and open quiescent combustion chamber to minimize heat transfer losses

Development and pilot evaluation of a personalized decision support intervention for low risk prostate cancer patients.

ObjectivesDevelopment and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.MethodsWe developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."ResultsThe development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).ConclusionsThe intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings

Intense exercise for survival among men with metastatic castrate-resistant prostate cancer (INTERVAL-GAP4): A multicentre, randomized, controlled phase III study protocol

Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatmentnaive for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant’s fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. Trial registration number: NCT02730338

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness

Series hybrid vehicles and optimized hydrogen engine design

Lawrence Livermore, Sandia Livermore and Los Alamos National Laboratories have a joint project to develop an optimized hydrogen fueled engine for series hybrid automobiles. The major divisions of responsibility are: system analysis, engine design and kinetics modeling by LLNL; performance and emission testing, and friction reduction by SNL; computational fluid mechanics and combustion modeling by LANL. This project is a component of the Department of Energy, Office of Utility Technology, National Hydrogen Program. We report here on the progress on system analysis and preliminary engine testing. We have done system studies of series hybrid automobiles that approach the PNGV design goal of 34 km/liter (80 mpg), for 384 km (240 mi) and 608 km (380 mi) ranges. Our results indicate that such a vehicle appears feasible using an optimized hydrogen engine. The impact of various on-board storage options on fuel economy are evaluated. Experiments with an available engine at the Sandia Combustion Research Facility demonstrated NO{sub x} emissions of 10 to 20 ppm at an equivalence ratio of 0.4, rising to about 500 ppm at 0.5 equivalence ratio using neat hydrogen. Hybrid vehicle simulation studies indicate that exhaust NO{sub x} concentrations must be less than 180 ppm to meet the 0.2 g/mile California Air Resources Board ULEV or Federal Tier II emissions regulations. We have designed and fabricated a first generation optimized hydrogen engine head for use on an existing single cylinder Onan engine. This head currently features 14.8:1 compression ratio, dual ignition, water cooling, two valves and open quiescent combustion chamber to minimize heat transfer losses

Vitamin D Levels in Patients with Colorectal Cancer and Matched Household Members.

Vitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients. Thirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/- 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise. Median serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P&gt;0.05). Household members were more likely than CRC patients to be overweight and to exercise more. Vitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted

APOL1 Risk Variants Associate With the Prevalence of Stroke in African American Current and Past Smokers

BackgroundAfrican American smokers have 2.5 times higher risk for stroke compared with nonsmokers (higher than other races). About 50% of the African American population carry 1 or 2 genetic variants (G1 and G2; rare in other races) of the apolipoprotein L1 gene (APOL1). Studies showed these variants may be associated with stroke. However, the role of the APOL1 risk variants in tobacco-related stroke is unknown.Methods and resultsIn a cross-sectional study, we examined whether APOL1 risk variants modified the relationship between tobacco smoking and stroke prevalence in 513 African American adults recruited at University of California, San Francisco. Using DNA, plasma, and questionnaires we determined APOL1 variants, smoking status, and stroke prevalence. Using logistic regression models, we examined the association between smoking (ever versus never smokers) and stroke overall, and among carriers of APOL1 risk variants (1 or 2 risk alleles), and noncarriers, separately. Among participants, 41% were ever (current and past) smokers, 54% were carriers of the APOL1 risk variants, and 41 had a history of stroke. The association between smoking and stroke differed by APOL1 genotype (Pinteraction term=0.014). Among carriers, ever versus never smokers had odds ratio (OR) 2.46 (95% CI, 1.08-5.59) for stroke (P=0.034); OR 2.00 (95% CI, 0.81-4.96) among carriers of 1 risk allele, and OR 4.72 (95% CI, 0.62-36.02) for 2 risk alleles. Among noncarriers, smoking was not associated with a stroke.ConclusionsCurrent and past smokers who carry APOL1 G1 and/or G2 risk variants may be more susceptible to stroke among the African American population