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Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. Methods Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration and safety. Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers were also performed. Results Thirty-two patients were enrolled of whom 88 % had received no prior chemotherapy. The median number of SB939 cycles administered was three (range 1-8). Adverse events were generally grade 1-2, with five pts experiencing one or more grade three event. One patient died due to myocardial infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and 21.6 months. In patients with measurable disease there were no objective responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC response (from ≥5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable patients (64 %). Conclusion Although SB939 was tolerable at the dose/schedule given, and showed declines in CTC in the majority of evaluable patients, it did not show sufficient activity based on PSA RR to warrant further study as a single agent in unselected patients with CRPC. [ABSTRACT FROM AUTHOR]

Background: Regular participation in strength exercise is important to promote healthy aging. However, much of the available evidence on physical activity and older adults has focused on aerobic activity, while there is less research on the benefits of exercise that is performed specifically to strengthen muscles., Aims: Using cross-sectional data from the Canadian Longitudinal Study on Aging, the purpose of this study was to determine if strength training is associated with better functional fitness and health among older adults who meet the minimum guidelines for aerobic physical activity., Methods: Older adults who met guidelines for aerobic physical activity (≥ 60 years, N = 9100) completed performance-based assessments of physical function and self-reported their physical activity, perceived health, and chronic conditions. Body fat was determined using DEXA. Logistic regression analyses were used to determine whether strength training was associated with better functional fitness, body composition, and health., Results: 32.5% of active older adults reported engaging in strength training 1-7 days per week. Participating in any strength training was associated with better scores on measures of balance (OR 1.17, CI 1.04, 1.32), mobility (OR 1.32, CI 1.18, 1.47), body fatness (OR 1.58, CI 1.38, 1.81), and better perceived health (OR 1.34, CI 1.19, 1.51), and healthy aging (OR 1.26, CI 1.12, 1.42)., Discussion: These results suggest that all older adults, even those who are active and have good mobility, may benefit from strength training., Conclusion: Physical activity guidelines should place a greater emphasis on strength training for older adults.

Background: Sitting time and physical activity may be modifiable determinants of lung function. The purpose of this study was to assess the effect that replacing various movement behaviours has on lung function among individuals with and without obstructive lung disease., Data and Methods: For analysis, data were used from participants of the Canadian Longitudinal Study on Aging, recruited between 2012 and 2015. Lung function was assessed using spirometry. A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels. Isotemporal substitution analysis was performed to analyze the effects of replacing 30 minutes per day of one movement behaviour with another, keeping the total time constant. Analyses were run separately for individuals with an obstructive lung disease (asthma, chronic obstructive pulmonary disease, or forced expiratory volume in 1 second [FEV₁] ⟨ 5th percentile lower limit of normal; n=3,398), and healthy adults (n=14,707)., Results: When sitting time was replaced with 30 minutes per day of any type of physical activity or sleep, an increase in percent (%) of predicted FEV₁ (i.e., β=0.65, confidence interval [CI]: 0.43, 0.88 for replacing sitting time with strenuous or strengthening activity) was observed among healthy adults. Among adults with obstructive lung disease, replacing 30 minutes per day of sitting time or sleep duration with strenuous or strengthening activity was associated with an improvement in the percent of predicted FEV₁ (i.e., β=0.98, CI: 0.13, 1.82 for replacing sleep duration with strenuous or strengthening activity)., Discussion: Replacing sitting time with physical activity leads to significant improvements in lung function among adults with an obstructive lung disease, as well as among adults without a respiratory disease.

Background: Physical activity has been shown to attenuate the age-associated decline in lung function; however, there is little research evaluating different movement behaviours as potential correlates of lung function. Modifiable determinants need to be identified, as the prevalence of chronic respiratory disease is on the rise. The purpose of this study was to investigate associations of self-reported movement behaviours (i.e., sitting time, walking, different intensities of physical activity, and strengthening activities), with lung function in middle-aged and older adults without a respiratory disease, according to their smoking history., Methods: Data from participants of the Canadian Longitudinal Study on Aging were used for analysis (n = 16,839). Lung function was assessed using spirometry. A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels. Smoking status was classified as non-smoking, < 10 pack years smoking, and 10 or more pack years of smoking. The association between movement behaviours and lung function was assessed using hierarchical linear regression models with all covariates (age, sex, smoking status, body mass index, education, retirement status, and sleep duration) entered into block 1, and all movement behaviours entered into block 2., Results: All movement behaviours were associated with Forced Expiratory Volume in 1 s (FEV 1 ) and Forced Vital Capacity (FVC) % predicted in crude and adjusted models, regardless of smoking status. Sitting time was negatively associated with both FEV 1%pred (β: -0.094, CI: -0.140, - 0.047) and FVC %pred (β: -0.087, CI: -0.128, -0.045) among those who never smoked, and strength activity was positively associated with both FEV 1%pred (β: 0.272, CI: 0.048, 0.496) and FVC %pred (β: 0.253, CI: 0.063,0.442) among those who smoked < 10 pack years, as well as with FVC %pred among those who smoked 10 or more pack years (β: 0.309, CI: 0.064, 0.554)., Conclusions: This is the first study to assess the association of different movement behaviours with lung function among middle-aged and older adults without a respiratory disease. These findings indicate that movement behaviours are correlates of lung function, and that they may be modifiable determinants of the age-associated decline in lung function.

Cascading speciation is predicted to occur when multiple interacting species diverge in parallel as a result of divergence in one species promoting adaptive differentiation in other species. However, there are few examples where ecological interactions among taxa have been shown to result in speciation that cascades across multiple trophic levels. Here, we test for cascading speciation occurring among the western pine beetle ( Dendroctonus brevicomis ), its primary host tree ( Pinus ponderosa ), and the beetle's fungal mutualists ( Ceratocystiopsis brevicomi and Entomocorticium sp. B). We assembled genomes for the beetle and a fungal symbiont and then generated reduced representation genomic data (RADseq) from range-wide samples of these three interacting species. Combined with published data for the host tree, we present clear evidence that the tree, the beetle, and the fungal symbionts are all genetically structured into at least two distinct groups that have strongly codiverged with geographical isolation. We then combine our genomic results with diverse population and laboratory-based data to show evidence for reproductive isolation at each level of the cascade and for coevolution of both antagonistic and mutualistic species interactions within this complex network., (© 2018 The Author(s).)

Background: The purpose of the current study was to determine the association between sedentary time and physical activity with clinically relevant health outcomes among adults with impaired spirometry and those with or without self-reported obstructive lung disease (asthma or COPD)., Methods: Data from participants of the Canadian Longitudinal Study on Aging were used for analysis (n = 4156). Lung function was assessed using spirometry. Adults were said to have impaired spirometry if their Forced Expiratory Volume in 1 s was <5th percentile lower limit of normal (LLN). A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels. Healthcare use and quality of life outcomes were assessed using self report., Results: Among those with asthma, participating in strengthening activities was associated with lower odds of reporting poor perceived health (OR = 0.65, CI: 0.53, 0.79), poor perceived mental-health (OR = 0.73, CI: 0.60, 0.88), unhealthy aging (OR = 0.68, CI: 0.56, 0.83), and reporting an emergency department visit in the past 12 months (OR = 0.76, CI: 0.60, 0.95). Among those with COPD, those who reported highest weekly sedentary time had higher odds of reporting poor perceived health (OR = 2.70, CI: 1.72, 4.24), poor perceived mental-health (OR = 1.99, CI: 1.29, 3.06), and unhealthy aging (OR = 3.04, CI: 1.96, 4.72). Among those below the LLN, sitting time (OR = 2.57, CI: 1.40, 4.72) and moderate intensity physical activity (OR = 0.23, CI: 0.09, 0.63) were associated with overnight hospital stays., Conclusions: Higher physical activity levels and lower sedentary time may be associated with lower healthcare use and better quality of life. This research may have implications related to the use of physical activity for improving health outcomes and quality of life among adults with obstructive lung disease or impaired spirometry.