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Measures of forest productivity generally rely on site index, which can be problematic for multicohort and mixed-species stands. Using stand growth and dominant tree height-age (i.e., site tree) measurements from ∼10 900 plot locations from Maine, Nova Scotia, New Brunswick, and Prince Edward Island, a forest productivity model for the Acadian Forest Region was developed as a function of climate, lithology, soils, and topographic metrics. Approximately 65% of variation in observed aboveground dry-biomass growth rate (BG) was explained by a Chapman-Richards function of temperature, bedrock, soil root space, slope, and depth to water in combination with stand structure and species predictors. Productivity was then defined in terms of the predicted asymptote of BG, holding structure and species constant, which was termed biomass growth index (BGI), i.e., the site-influenced component of the BG relationship. BGI was mapped on a 20 m grid throughout the region. BGI explained 0%-30% of the variability in spruce ( Picea sp.) and balsam fir ( Abies balsamea (L.) Mill.) site index and had similar site index predictive performance (±5%) when compared with existing land productivity classifications in each province. BGI provides a direct relationship between site variables and growth and can help guide forest management decisions and future research. [ABSTRACT FROM AUTHOR]

A response by Steven E. Riechman, Ryan D. Andrews, David A. MacLean, and Simon Sheater to a letter to the editor about their article "Statins and dietary and blood cholesterol are associated with increased mass following resistance training" is presented.

Introduction: Sarcopenia is disproportionately present in older women with disability, and optimum treatment is not clear. We conducted a double-blind, randomized, placebo-controlled trial to determine whether oxandrolone administration in elderly women improves body composition or physical function beyond that which occurs in response to progressive resistance training (PRT). Methods: Twenty-nine sedentary women (age 74.9 ± 6.8 yr; 5.9 ± 2.8 medications per day) were randomized to receive high-intensity PRT (three times a week for 12 wk) combined with either oxandrolone (10 mg⋅d-1) or an identical placebo. Peak strength was assessed for leg press, chest press, triceps, knee extension, and knee flexion. Power was assessed for leg press and chest press. Physical function measures included static and dynamic balance, chair rise, stair climb, gait speed, and 6-min walk test. Body composition was assessed using dual energy x-ray absorptiometry. Results: Oxandrolone treatment augmented increases in lean tissue for the whole body (2.6 kg; 95% confidence interval (CI), 1.0-4.2 kg; P = 0.003), arms (0.3 kg; 95% CI, 0.1-0.5 kg; P = 0.001), legs (0.8 kg; 95% CI, 0.1-1.4 kg; P = 0.018), and trunk (1.4 kg; 95% CI, 0.4-2.3 kg; P = 0.004). Oxandrolone also augmented loss of fat tissue of the whole body (-1 kg; 95% CI, -1.6 to -0.4; P = 0.002), arms (-0.2 kg; 95% CI, -0.5 to -0.02 kg; P = 0.032), legs (-0.4 kg; 95% CI, -0.6 to -0.1; P = 0.009), and tended to reduce trunk fat (-0.4 kg; 95% CI, -0.9 to 0.04; P = 0.07). Improvements in muscle strength and power, chair stand, and dynamic balance were all significant over time (P < 0.05) but not different between groups (P > 0.05). Conclusions: Oxandrolone improves body composition adaptations to PRT in older women over 12 wk without augmenting muscle function or functional performance beyond that of PRT alone. [ABSTRACT FROM AUTHOR]

Global climate is changing due to increasing anthropogenic emissions of greenhouse gases. Forest managers need growth and yield models that can be used to predict future forest dynamics during the transition period of present-day forests under a changing climatic regime. In this study, we developed a forest growth and yield model that can be used to predict individual-tree growth under current and projected future climatic conditions. The model was constructed by integrating historical tree growth records with predictions from an ecological process-based model using neural networks. The new model predicts basal area (BA) and volume growth for individual trees in pure or mixed species forests. For model development, tree-growth data under current climatic conditions were obtained using over 3000 permanent sample plots from the Province of Nova Scotia, Canada. Data to reflect tree growth under a changing climatic regime were projected with JABOWA-3 (an ecological process-based model). Model validation with designated data produced model efficiencies of 0.82 and 0.89 in predicting individual-tree BA and volume growth. Model efficiency is a relative index of model performance, where 1 indicates an ideal fit, while values lower than zero means the predictions are no better than the average of the observations. Overall mean prediction error (BIAS) of basal area and volume growth predictions was nominal (i.e., for BA: -0.0177 cm2 5-year-1 and volume: 0.0008 m3 5-year-1). Model variability described by root mean squared error (RMSE) in basal area prediction was 40.53 cm2 5-year-1 and 0.0393 m3 5-year-1 in volume prediction. The new modelling approach has potential to reduce uncertainties in growth and yield predictions under different climate change scenarios. This novel approach provides an avenue for forest managers to generate required information for the management of forests in transitional periods of climate change. Artificial intelligence technology has substantial potential in forest modelling. [ABSTRACT FROM AUTHOR]

Summary Background Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this phase 3, double-blind, placebo-controlled trial, we recruited patients with progressive metastatic castration-resistant prostate cancer and no previous chemotherapy from 324 study centres (ie, hospitals or large urologic or group outpatient offices) in 43 countries. Eligible patients were randomly assigned in a 1:1 ratio to receive either 400 mg orteronel plus 5 mg prednisone twice daily or placebo plus 5 mg prednisone twice daily. Randomisation was done centrally with an interactive voice response system and patients were stratified by region (Europe, North America, and not Europe or North America) and the presence or absence of radiographic disease progression at baseline. The two primary endpoints were radiographic progression-free survival and overall survival, determined in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01193244 . Findings From Oct 31, 2010, to June 29, 2012, 2353 patients were assessed for eligibility. Of those, 1560 were randomly assigned to receive either orteronel plus prednisone (n=781) or placebo plus prednisone (n=779). The clinical cutoff date for the final analysis was Jan 15, 2014 (with 611 deaths). Median follow-up for radiographic progression-free survival was 8·4 months (IQR 3·7–16·6). Median radiographic progression-free survival was 13·8 months (95% CI 13·1–14·9) with orteronel plus prednisone and 8·7 months (8·3–10·9) with placebo plus prednisone (hazard ratio [HR] 0·71, 95% CI 0·63–0·80; p<0·0001). After a median follow-up of 20·7 months (IQR 14·2–25·4), median overall survival was 31·4 months (95% CI 28·6–not estimable) with orteronel plus prednisone and 29·5 months (27·0–not estimable) with placebo plus prednisone (HR 0·92, 95% CI 0·79–1·08; p=0·31). The most common grade 3 or worse adverse events were increased lipase (137 [17%] of 784 patients in the orteronel plus prednisone group vs 14 [2%] of 770 patients in the placebo plus prednisone group), increased amylase (77 [10%] vs nine [1%]), fatigue (50 [6%] vs 14 [2%]), and pulmonary embolism (40 [5%] vs 27 [4%]). Serious adverse events were reported in 358 [46%] patients receiving orteronel plus prednisone and in 292 [38%] patients receiving placebo plus prednisone. Interpretation In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone. However, no improvement was noted in the other primary endpoint, overall survival. Orteronel plus prednisone was associated with increased toxic effects compared with placebo plus prednisone. On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer. Funding Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. [ABSTRACT FROM AUTHOR]

Growth and yield models are critically important for forest management planning. Biophysical factors such as light, temperature, soil water, and nutrient conditions are known to have major impacts on tree growth. However, it is difficult to incorporate these biophysical variables into growth and yield models due to large variation and complex nonlinear relationships between variables. In this study, artificial intelligence technology was used to develop individual-tree-based basal area (BA) and volume increment models. The models successfully account for the effects of incident solar radiation, growing degree days, and indices of soil water and nutrient availability on BA and volume increments of over 40 species at 5-year intervals. The models were developed using data from over 3000 permanent sample plots across the province of Nova Scotia, Canada. Model validation with independent field data produced model efficiencies of 0.38 and 0.60 for the predictions of BA and volume increments, respectively. The models are applicable to predict tree growth in mixed species, even- or uneven-aged forests in Nova Scotia but can easily be calibrated for other climatic and geographic regions. Artificial neural network models demonstrated better prediction accuracy than conventional regression-based approaches. Artificial intelligence techniques have considerable potential in forest growth and yield modelling. [ABSTRACT FROM AUTHOR]

Aims Two randomized, double-blind, placebo-controlled studies were performed to characterize the safety, tolerability, pharmacokinetics ( PK) and pharmacodynamics ( PD) of the investigational metastin analogue, TAK-683, in healthy men. Methods We first investigated a single subcutaneous ( s.c.) dose of TAK-683 (0.01-2.0 mg) in 60 subjects ( TAK-683, n = 42; placebo, n = 18). We then assessed a single s.c. bolus of 0.03-1.0 mg TAK-683 on day 1, followed by a 0.01-2.0 mg day−1 continuous infusion on days 2-13, to simulate a depot formulation, in 30 subjects ( TAK-683, n = 25; placebo, n = 5) for 14 days. Results TAK-683 was well tolerated up to a dose of 2.0 mg day−1 by continuous s.c. infusion for 14 days. Adverse events were similar between TAK-683 and placebo subjects at all dose levels. TAK-683 plasma concentrations generally increased in proportion to dose with single and continuous dosing, with steady-state concentrations achieved by day 2 of continuous dosing. TAK-683 at 2.0 mg day−1 suppressed testosterone below castration level (<50 ng dl−1) in four of five subjects by day 7 of continuous dosing. Luteinizing hormone and follicle stimulating hormone concentrations were suppressed with TAK-683 continuous dosing compared with placebo by up to 70 and 43%, respectively, but this was not consistently dose-dependent. Conclusions In healthy men, s.c. administration of TAK-683 was well tolerated at all dose levels. The PK profile of TAK-683 was favourable, and TAK-683 suppressed testosterone profoundly during continuous dosing. Further investigation of metastin analogues is warranted for the treatment of castration-resistant prostate cancer. [ABSTRACT FROM AUTHOR]

We have investigated the range of cleft closure conformational states that the agonist-binding domains of the α-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors occupy when bound to a series of willardiine derivatives using single-molecule FRET. These studies show that the agonist- binding domain exhibits varying degrees of dynamics when bound to the different willardiines with differing efficacies. The chlorowillardiine- and nitrowillardiine-bound form of the agonist- binding domain probes a narrower range of cleft closure states relative to the iodowillardiine bound form of the protein, with the antagonist (αS)-α-amino-3-[(4-carboxyphenyl)methyl]-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinepropanoic acid (UBP-282)-bound form exhibiting the widest range of cleft closure states. Additionally, the average cleft closure follows the order UBP-282 > iodowillardiine > chlorowillardiine > nitrowillardiine-bound forms of agonist-binding domain. These single-molecule FRET data, along with our previously reported data for the glutamate-bound forms of wild type and T686S mutant proteins, show that the mean currents under nondesensitizing conditions can be directly correlated to the fraction of the agonist-binding domains in the "closed" cleft conformation. These results indicate that channel opening in theAMPAreceptors is controlled by both the ability of the agonist to induce cleft closure and the dynamics of the agonist-binding domain when bound to the agonist. [ABSTRACT FROM AUTHOR]

It is well established that there is a differential distribution of the nitric oxide synthases (NOS; neuronal, eNOS; inducible, iNOS and endothelial, eNOS) in skeletal muscle which differ in their quantitative expression depending on tissue and species. In humans, nNOS expression has been found to be similar in both type I and type II skeletal muscle fibers, while in rodents an increase in the expression of nNOS in type II fibers as compared to type I fibers has been observed. It has also been suggested that hypertension may alter the expression of nNOS in skeletal muscle, however, very few direct measurements of nNOS expression or nitric oxide (NO) concentrations have been made under these conditions. Therefore, the purpose of the present study was to determine NO concentrations in the white gastrocnemius (WG) and soleus (S) muscle of WKY (control) and spontaneously hypertensive rats (SHR). Basal WG NO levels were consistently lower, but not different (P>0.05) between WKY and SHR rats, While S NO levels were also similar between groups. However, the WKY and SHR groups showed a 27±7% and 11±3% higher (P<0.05) NO concentration in the WG as compared the S muscle, respectively. These data demonstrate that hypertension does not result in any significant changes in the basal levels of NO in rat WG and S muscle and may be explained by the fact these measurements were made on resting skeletal muscle. However, this study clearly showed a greater NO concentration in type II versus type I muscle fibers. Supported by NSERC [ABSTRACT FROM AUTHOR]

We investigated the potential economic impacts of future spruce budworm (SBW) ( (Clemens)) outbreaks on 2.8 million hectares of Crown forest land in New Brunswick by coupling an advanced Spruce Budworm Decision Support System (SBW DSS) model with a dynamic computable general equilibrium model. A total of 16 alternative scenarios were evaluated, including two SBW outbreak severities (moderate versus severe), four SBW control program levels (protecting 0%, 10%, 20%, and 40% of susceptible Crown land forest area), and two pest management strategies ('without' versus 'with' replanning harvest scheduling and salvage). The 'without' replanning harvest scheduling and salvage strategy findings indicated that, under uncontrolled moderate and severe SBW outbreaks, total output in the New Brunswick economy over the 2012-2041 period would decline in present-value terms by CDN$3.3 billion and $4.7 billion, respectively. SBW control via aerial spraying was shown to reduce the negative impacts on output by up to 66% when protecting 40% of susceptible area. Combining SBW control with replanning harvest scheduling and salvage strategy under moderate and severe outbreaks would reduce the negative impacts on output by a further 1%-18% depending on the level of control implemented. These findings can help forest managers assess the direct and indirect economic effects of forest pest disturbances on regional economies and can also be used together with other sustainable forest management indicators to help broaden the scope of SBW and other forest pest management decision-making. [ABSTRACT FROM AUTHOR]

This study employs a benefit-cost analysis framework to estimate market and non-market benefits and costs of controlling future spruce budworm (Choristoneura fumiferana) outbreaks on Crown forest lands in New Brunswick, Canada. We used: (i) an advanced timber supply model to project potential timber volume saved, timber value benefits, and costs of pest control efforts; and (ii) a recent contingent valuation method analysis that evaluated non-market benefits (i.e., changes in recreation opportunities and existence values) of controlling future spruce budworm outbreaks in the Province. A total of six alternative scenarios were evaluated, including two uncontrolled future budworm outbreak severities (moderate vs. severe) and, for each severity, three control program levels (protecting 10%, 20%, or 40% of the susceptible Crown land forest area). The economic criteria used to evaluate each scenario included benefit-cost ratios and net present values. Under severe outbreak conditions, results indicated that the highest benefit-cost ratio (4.04) occurred when protecting 10% (284,000 ha) of the susceptible area, and the highest net present value ($111 M) occurred when protecting 20% (568,000 ha) of the susceptible area. Under moderate outbreak conditions, the highest benefit-cost ratio (3.24) and net present value ($58.7 M) occurred when protecting 10% (284,000 ha) of the susceptible area. Inclusion of non-market values generally increased the benefit-cost ratios and net present values of the control programs, and in some cases, led to higher levels of control being supported. Results of this study highlight the importance of including non-market values into the decision making process of forest pest management. [Copyright &y& Elsevier]

Background: Since proteins involved in chemotherapy drug pharmacokinetics and pharmacodynamics have a strong impact on the uptake, metabolism, and efflux of such drugs, they likely play critical roles in resistance to chemotherapy drugs in cancer patients.Methods: To investigate this hypothesis, we conducted a whole genome microarray study to identify difference in the expression of genes between isogenic doxorubicin-sensitive and doxorubicin-resistant MCF-7 breast tumour cells. We then assessed the degree of over-representation of doxorubicin pharmacokinetic and pharmacodynamic genes in the dataset of doxorubicin resistance genes.Results: Of 27,958 Entrez genes on the array, 7.4 per cent or 2,063 genes were differentially expressed by ≥ 2-fold between wildtype and doxorubicin-resistant cells. The false discovery rate was set at 0.01 and the minimum p value for significance for any gene within the “hit list” was 0.01. Seventeen and 43 per cent of doxorubicinpharmacokinetic genes were over-represented in the hit list, depending upon whether the gene name was identical or within the same gene family, respectively. The most over-represented genes were within the 1C and 1B families of aldo-keto reductases (AKRs), which convert doxorubicin to doxorubicinol. Other genes convert doxorubicin to other metabolites or affect the influx, efflux, or cytotoxicity of the drug. In further support of the role of AKRs in doxorubicin resistance, we observed that, in comparison to doxorubicin, doxorubincol exhibiteddramatically reduced cytotoxicity, reduced DNA-binding activity, and strong localization to extra nuclear lysosomes.Pharmacologic inhibition of the above AKRs in doxorubicin-resistant cells increased cellular doxorubicin levels,restored doxorubicin cytotoxicity and re-established doxorubicin localization to the nucleus. The properties of doxorubicinol were unaffected.Conclusions: These findings demonstrate the utility of using curated pharmacokinetic and pharmacodynamicknowledge bases to identify highly relevant genes associated with doxorubicin resistance. The induction of one or more of these genes was found to be correlated with changes in the drug’s properties, while inhibiting one specific class of these genes (the AKRs) increased cellular doxorubicin content and restored drug DNA binding, cytotoxicity,and subcellular localization. [ABSTRACT FROM AUTHOR]

Spruce budworm ( Choristoneura fumiferana Clem.) is an important and recurrent disturbance throughout spruce ( Picea sp.) and balsam fir ( Abies balsamea L.) dominated forests of North America. Forest carbon (C) dynamics in these ecosystems are affected during insect outbreaks because millions of square kilometers of forest suffer growth loss and mortality. We tested the hypothesis that a spruce budworm outbreak similar to those in the past could switch a forest from a C sink to a source in the near future. We used a model of ecosystem C to integrate past spruce budworm impact sequences with current forest management data on 106,000 km of forest in eastern Québec. Spruce budworm-caused mortality decreased stand-level merchantable C stocks by 11–90% and decreased ecosystem C stocks by 2–10% by the end of the simulation. For the first 13 years (2011–2024), adding spruce budworm significantly reduced ecosystem C stock change for the landscape from a sink (4.6 ± 2.7 g C m y in 2018) to a source (−16.8 ± 3.0 g C m y in 2018). This result was mostly due to reduced net primary production. The ecosystem stock change was reduced on average by 2 Tg C y for the entire simulated area. This study provides the first estimate that spruce budworm can significantly affect the C sink or source status of a large landscape. These results indicate that reducing spruce budworm impacts on timber may also provide an opportunity to mitigate a C source. [ABSTRACT FROM AUTHOR]

Recent studies suggest that tumor cells overexpressing aldoketoreductases (AKRs) exhibit increased resistance to DNA damaging agents such as anthracyclines. AKRs may induce resistance to the anthracycline doxorubicin by catalyzing its conversion to the less toxic 13-hydroxy metabolite doxorubicinol. However, it has not been established whether during selection for anthracycline resistance, AKR overexpression in tumor cells can be correlated with the onset or magnitude of drug resistance and with appreciable conversion of anthracyclines to 13-hydroxy metabolites.Through microarray and quantitative polymerase chain reaction studies involving rigid selection criteria and both correlative discriminate statistics and time-course models, we have identified several genes whose expression can be correlated with the onset and/or magnitude of anthracycline resistance, including AKR1C2 and AKR1C3. Also associated with the onset or magnitude of anthracycline resistance were genes involved in drug transport (ABCB1, ABCC1), cell signaling and transcription (RDC1, CXCR4), cell proliferation or apoptosis (BMP7, CAV1), protection from reactive oxygen species (AKR1C2, AKR1C3, FTL, FTH, TXNRD1, MT2A), and structural or immune system proteins (IFI30, STMN1). As expected, doxorubicin-resistant and epirubicin-resistant cells exhibited higher levels of doxorubicinol than wild-type cells, although at insufficient levels to account for significant drug resistance. Nevertheless, an inhibitor of Akr1c2 (5β-cholanic acid) almost completely restored sensitivity to doxorubicin in ABCB1-deficient doxorubicin-resistant cells, while having no effect on ABCB1-expressing epirubicin-resistant cells.Taken together, we show for the first time that a variety of genes (particularly redox genes such as AKR1C2 and AKR1C3) can be temporally and causally correlated with the acquisition of anthracycline resistance in breast tumor cells. [ABSTRACT FROM AUTHOR]

Systemic hypoxia leads to peripheral vasodilation that serves to counteract the decrease in peripheral oxygen (O(2)) delivery. Skeletal muscle vasodilation associated with hypoxia is due to release of vasodilator substances such as adenosine and/or nitric oxide (NO). We hypothesized that skeletal muscle may act as a source of NO during exposure to hypoxia. Therefore, we measured NO in forearm venous plasma and in skeletal muscle interstitial dialysate in seven healthy young men during exposure to simulated altitude of 2,438 and 4,877 m (20 min at each level) in a hypobaric chamber. O(2) saturation (mean +/- SEM) fell from 98.0 +/- 0.2% at ambient conditions to 91.0 +/- 0.4% at 2,438 m and to 73.2 +/- 4.4% at 4,877 m (P < 0.05). While blood pressure remained unchanged, heart rate increased in a graded fashion (P < 0.05). Plasma NO (chemiluminescence method) rose from 11.6 +/- 1.3 to 16.9 +/- 2.9 microM at 2,438 m (P < 0.05) but remained similar at 16.4 +/- 2.3 microM at 4,877 m (NS). In contrast, skeletal muscle microdialysate NO levels were lower than plasma NO (P < 0.01) and did not change during simulated altitude. Thus, hypoxia produced by simulated high altitude exposure leads to an increase in plasma but not skeletal muscle interstitial NO. These data support an important role of NO in the peripheral vascular responses to hypoxia. The differential responses of plasma vs. interstitial NO during hypoxia suggest an endothelial or intravascular source of NO. [ABSTRACT FROM AUTHOR]

Abstract: In Canada, fire danger is rated by the Canadian forest fire danger rating system (CFFDRS). One of its components is the fire weather index (FWI) system, which has among others the drought code (DC). DC is used here as a surrogate of dead forest fuel moisture. DC values were computed from weather data acquired between 1993 and 1999 and compared to 10-day composite NOAA-AVHRR images acquired over Canadian northern boreal forests. They were yearly correlated with single compositing period and cumulative NDVI and surface temperature (ST) NOAA-AVHRR data. Correlations with cumulative spectral variables were stronger than with single compositing period variables and the best correlations occurred for the spring compositing periods (R between 0.57 and 0.80). Spring DC models using both single compositing period and cumulative spectral variables were established. Surface temperature-based indices were more often used in the models than NDVI-based indices. The models were stronger for dry or normal years than for wet years. Limitations and possible improvements of the models are discussed. [Copyright &y& Elsevier]

This investigation evaluated the physiological impact of different dietary protein intakes on skeletal muscle protein synthesis postexercise in endurance runners. Five endurance-trained, male runners participated in a randomized, crossover design diet intervention, where they consumed either a low (0.8 g/kg; LP)-, moderate (1.8 g/kg; MP)-, or high (3.6 g/kg; HP)-protein diet for 4 wk. Diets were designed to be eucaloric with carbohydrate, fat, and protein approximating 60, 30, and 10%; 55, 30, and 15%; and 40, 30, and 30% for LP, MP, and HP, respectively. Substrate oxidation was assessed via indirect calorimetry at 3 wk of the dietary interventions. Mixed-muscle protein fractional synthetic rate (FSR) was measured after an endurance run (75 rain at 70% VO2 peak) using a primed, continuous infusion of [²H5]phenylalanine. Protein oxidation increased with increasing protein intake, with each trial being significantly different from the other (P « 0.01). FSR after exercise was significantly greater for LP (0.083%/h) and MP (0.078%/h) than for HP (0.052%/h; P « 0.05). There was no difference in FSR between LP and MP. This is the first investigation to establish that habitual dietary protein intake in humans modulates skeletal muscle protein synthesis after an endurance exercise bout. Future studies directed at mechanisms by which level of protein intake influences skeletal muscle turnover are needed. [ABSTRACT FROM AUTHOR]

Purpose: Depression is a risk factor for incident coronary heart disease (CHD), and predicts poor prognosis for patients post-myocardial infarction (MI). Few population-based, prospective studies have tested a gradient risk for depressive symptoms on CHD incidence. Methods: The sample (n=1302) was derived from the Nova Scotia Health Survey–1995 (NSHS95), an age- and sex-stratified, random, population-based health survey. All subjects were 45 years or older, free of overt CHD at baseline, and completed the Center for Epidemiological Studies-Depression (CES-D) scale. Covariates included age, sex, body mass index, physical activity level, family history of premature CHD, diastolic blood pressure, lipids, smoking, alcohol use, diabetes, and education level. For the 4 years following NSHS95, MI-related hospitalizations (ICD-9-CM code 410) and CHD-related deaths (ICD-9-CM codes 410–414) were extracted from the provincial, universal healthcare registry. Results: Fifty-two participants experienced a CHD event. A one standard-deviation increase in CES-D score was associated with a 1.32 hazard risk (confidence interval, 1.01–1.71) of CHD events, controlling for established CHD risk factors. Conclusions: An independent, gradient association between depression and incident CHD was detected in a population-based sample with complete 4-year CHD data. This evidence supports the value of investigating mechanisms linking depression and CHD. [Copyright &y& Elsevier]

This paper presents an operational definition of capacity building for heart health promotion, instruments developed to measure heart health capacity, and baseline results of capacity for 20 organizations. Qualitative and quantitative research methods were used to collect data. Three instruments were developed to measure organizational capacity for heart health promotion: a survey of community agencies involved in heart health, a questionnaire of organizational practices supportive of heart health promotion, and an interview guide that focused on factors influencing heart health promotion. These instruments proved effective and informed the development of a comprehensive framework for heart health promotion. [ABSTRACT FROM AUTHOR]

Currently, there are no in vivo techniques for quantifying healing within fractures involving mainly trabecular bone. Methods for quantitatively assessing healing would aid the investigation of new treatment regimes, and might also be useful for predicting whether a patient may be undergoing delayed union. Using CT and automated image registration, we have developed an image processing technique for measuring changes in CT image intensity at fracture sites. The technique focuses on quantifying the formation of new mineralised tissue within fracture gaps, while ignoring loss of bone mineral due to disuse osteoporosis. Seven patients with fractures of the distal radius were examined for 12 weeks following fracture. To assess reproducibility of measurements of change in CT intensity at the fracture line, measurements were performed on two separate occasions, by each of two independent readers. Reproducibility was compared to rates of change over time, to determine detectable differences in individual progression. Scans were scored qualitatively for features of healing and scores compared to the quantitative measurements. The mean (SD) change in CT intensity was +128 (65) Hounsfield Units (HU) over the 12 week follow-up. Inter- and intra-observer reproducibilities were both similar (±17 HU), 1/7 of the change seen during the study. In this small patient cohort, a significant increase in CT intensity was seen 2 weeks post-fracture. Large early increases in CT intensity were associated with early visual appearance of sclerosis and blurring of the fracture line. In this preliminary, prospective study, we have developed a reproducible quantitative technique for measuring changes in CT intensity of trabecular bone at the fracture line in the distal radius. Further work is required to determine whether it can be used to identify, or monitor patients who are undergoing delayed fracture repair. The technique appears sensitive for measuring changes immediately post-fracture, and could have a role in examining potential effects of new therapies in patient cohorts. [Copyright &y& Elsevier]

The authors describe the facilitators and challenges to a multisectoral initiative aiming at building organizational capacity for heart health promotion in Nova Scotia, Canada. The research process was guided by participatory action research. The study included 21 organizations from diverse sectors. Participant selection for the data collection was purposive. The authors collected data through organizational reflection logs and one-to-one semistructured interviews and used grounded theory techniques for the data analyses. Factors influencing organizational capacity for heart health promotion varied, depending on the project stage. Nonetheless, leadership, organizational readiness, congruence, research activities, technical supports, and partnerships were essential to capacity-building efforts. Approaches to organizational capacity building should be multileveled, because organizations are influenced by multiple social systems that are not all equally supportive of capacity. [ABSTRACT FROM AUTHOR]

: ObjectiveThere is an accumulating body of research related to the psychosomatic study of blood pressure. One variable that has received attention is defense use. We examined the relation between defense use and blood pressure in men and women of different ages.: MethodsA random sample of 667 participants was selected from a population-based study. Resting blood pressure was obtained, and each participant was rated for defense use by a trained observer using Defense-Q. An Adaptive Defense Profile (ADP) score was calculated for each participant, and this score was related to blood pressure.: ResultsRegression analyses revealed a significant main effect for the ADP score for both diastolic and systolic blood pressure. Those persons with higher ADP scores had lower diastolic and systolic blood pressure. As well, a significant Age×Sex×ADP score interaction was found for diastolic blood pressure. Older women with a less ADP score had higher diastolic blood pressure.: ConclusionThese findings suggest the continued investigation of defense use and blood pressure. [Copyright &y& Elsevier]

Presents a study that examined the time course changes in serum insulin concentrations in food-deprived rats after an oral bolus of leucine. Examination of the contribution of changes in serum concentrations of insulin to the increase in protein synthesis; Circulating insulin concentrations in food-deprived rats infused with somatostatin and leucine; Chemical essential for the enhanced rates of protein synthesis observed in skeletal muscle after food intake.

Some researchers have found higher cholesterol levels linearly related to hostility, whereas others have found no relation. Even so, it remains unclear whether research should seek to find a linear relation between hostility and cholesterol levels. We hypothesized that a U-curved association was the proper test of the relation between hostility and cholesterol. Total fasting and low-density lipoprotein (LDL) cholesterol levels were collected from a population-based sample of 2,306 Canadians. Barefoot's (1989) scoring of the Cook-Medley Hostility Scale was used to assess hostility levels. Both a linear and a U-curved relation among hostility scores, fasting total, and LDL cholesterol levels were significant. Participants with low and high cholesterol levels had significantly higher hostility scores than the normal cholesterol group. A U-curved relation between hostility and serum cholesterol levels may be a more appropriate function to consider given the all-cause mortality findings we seek to explain. [ABSTRACT FROM AUTHOR]

Examines the effects of dynamic one-legged knee extension exercise on mean blood velocity (MBV) and muscle interstitial metabolite concentrations in healthy young people. Examination of blood flow changes during exercise using Doppler ultrasound; Influence of exercise intensity on MBV and interstitial potassium and adenosine; Effect of exercise on the temporal pattern of response for MBV and interstitial adenosine.

Investigates the effect of dynamic exercise on mean blood velocity and muscle interstitial metabolite responses of humans. Increase in interstitial adenosine from rest to exercise; Role of potassium and adenosine in the regulation of skeletal muscle blood flow during.

OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 ± 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P = .0004) as well as the exercise alone (+47.8%, P = .0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P = .027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study. [ABSTRACT FROM AUTHOR]

Reports on the diagnostic and treatment policies of patients with coronary artery disease and in patients with mild or severe dyslipidemia. The Working Group on Hypercholesterolemia and Other Dyslipidemias that was established by Health Canada due to the progress of research; Recommendations that include screening patients for a fasting lipid profile, physical examinations for cholesterol disorders and atherosclerosis, and determining target lipid levels; Therapeutic strategy for patients with dyslipidemia.

Presents a study of population-based data from the Canadian Heart Health Surveys database concerning Canadians over 65 years old and their risk factors of cardiovascular disease. Background; Methods; Results; Interpretation and discussion.

Background: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. Methods: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. Results: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. Interpretation: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification. [ABSTRACT FROM AUTHOR]

Offers results of a study on trends in the prevalence and treatment of hypertension in Halifax County, Nova Scotia from 1985-1995. Background; Methods; Results; Interpretation.

Anorexia nervosa is a serious psychiatric disorder but the search for disease-modifying biological agents have yielded few options. This case describes the efficacious use of olanzapine off-label in weight restoration in an adolescent. However, occurrence of first-degree heart block during treatment flags up a need for cardiac monitoring with such treatment across this age group. [ABSTRACT FROM AUTHOR]

Examines the potential mechanism contributing to the inhibition of protein synthesis in skeletal muscle and heart after administration of tumor necrosis factors-α in rats. Reason behind reduction in synthesis of microfibrillar and sarcoplasmic proteins; Study of eukaryotic initiation factors and elongation factors; Relation between heart and skeletal muscle protein synthesis and messenger ribonucleic acid translational efficiency.