Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Sit versus stand : can sitting be accurately identified using MTI accelerometer data?

High levels of sitting have been linked with poor health outcomes. Previously a pragmatic MTI accelerometer data cut-point (100 count/min-1) has been used to estimate sitting. Data on the accuracy of this cut-point is unavailable. PURPOSE: To ascertain whether the 100 count/min-1 cut-point accurately isolates sitting from standing activities. METHODS: Participants fitted with an MTI accelerometer were observed performing a range of sitting, standing, light & moderate activities. 1-min epoch MTI data were matched to observed activities, then re-categorized as either sitting or not using the 100 count/min-1 cut-point. Self-report demographics and current physical activity were collected. Generalized estimating equation for repeated measures with a binary logistic model analyses (GEE), corrected for age, gender and BMI, were conducted to ascertain the odds of the MTI data being misclassified. RESULTS: Data were from 26 healthy subjects (8 men; 50% aged <25 years; mean BMI (SD) 22.7(3.8)m/kg2). MTI sitting and standing data mode was 0 count/min-1, with 46% of sitting activities and 21% of standing activities recording 0 count/min-1. The GEE was unable to accurately isolate sitting from standing activities using the 100 count/min-1 cut-point, since all sitting activities were incorrectly predicted as standing (p=0.05). To further explore the sensitivity of MTI data to delineate sitting from standing, the upper 95% confidence interval of the mean for the sitting activities (46 count/min-1) was used to re-categorise the data; this resulted in the GEE correctly classifying 49% of sitting, and 69% of standing activities. Using the 100 count/min-1 cut-point the data were re-categorised into a combined ‘sit/stand’ category and tested against other light activities: 88% of sit/stand and 87% of light activities were accurately predicted. Using Freedson’s moderate cut-point of 1952 count/min-1 the GEE accurately predicted 97% of light vs. 90% of moderate activities. CONCLUSION: The distributions of MTI recorded sitting and standing data overlap considerably, as such the 100 count/min -1 cut-point did not accurately isolate sitting from other static standing activities. The 100 count/min -1 cut-point more accurately predicted sit/stand vs. other movement orientated activities.

The effect of ocular surface conditions on blink rate and completeness

A healthy human would be expected to show periodic blinks, making a brief closure of the eyelids. Most blinks are spontaneous, occurring regularly with no external stimulus. However a reflex blink can occur in response to external stimuli such as a bright light, a sudden loud noise, or an object approaching toward the eyes. A voluntary or forced blink is another type of blink in which the person deliberately closes the eyes and the lower eyelid raises to meet the upper eyelid. A complete blink, in which the upper eyelid touches the lower eyelid, contributes to the health of ocular surface by providing a fresh layer of tears as well as maintaining optical integrity by providing a smooth tear film over the cornea. The rate of blinking and its completeness vary depending on the task undertaken during blink assessment, the direction of gaze, the emotional state of the subjects and the method under which the blink was measured. It is also well known that wearing contact lenses (both rigid and soft lenses) can induce significant changes in blink rate and completeness. It is been established that efficient blinking plays an important role in ocular surface health during contact lens wear and for improving contact lens performance and comfort. Inefficient blinking during contact lens wear may be related to a low blink rate or incomplete blinking and can often be a reason for dry eye symptoms or ocular surface staining. It has previously been shown that upward gaze can affect blink rate, causing it to become faster. In the first experiment, it was decided to expand on previous studies in this area by examining the effect of various gaze directions (i.e. upward gaze, primary gaze, downward gaze and lateral gaze) as well as head angle (recumbent position) on normal subjects’ blink rate and completeness through the use of filming with a high-speed camera. The results of this experiment showed that as the open palpebral aperture (and exposed ocular surface area) increased from downward gaze to upward gaze, the number of blinks significantly increased (p<0.04). Also, the size of closed palpebral aperture significantly increased from downward gaze to upward gaze (p<0.005). A weak positive correlation (R² = 0.18) between the blink rate and ocular surface area was found in this study. Also, it was found that the subjects showed 81% complete blinks, 19% incomplete blinks and 2% of twitch blinks in primary gaze, consistent with previous studies. The difference in the percentage of incomplete blinks between upward gaze and downward gaze was significant (p<0.004), showing more incomplete blinks in upward gaze. The findings of this experiment suggest that while blink rate becomes slower in downward gaze, the completeness of blinking is typically better, thereby potentially reducing the risk of tear instability. On the other hand, in upward gaze while the completeness of blinking becomes worse, this is potentially offset by increased blink frequency. In addition, blink rate and completeness were not affected by lateral gaze or head angle, possibly because these conditions have similar size of the open palpebral aperture compared with primary gaze. In the second experiment, an investigation into the changes in blink rate and completeness was carried out in primary gaze and downward gaze with soft and rigid contact lenses in unadapted wearers. Not surprisingly, rigid lens wear caused a significant increase in the blink rate in both primary (p<0.001) and downward gaze (p<0.02). After fitting rigid contact lenses, the closed palpebral aperture (blink completeness) did not show any changes but the open palpebral aperture showed a significant narrowing (p<0.04). This might occur from the subjects’ attempt to avoid interaction between the upper eyelid and the edge of the lens to minimize discomfort. After applying topical anaesthetic eye drops in the eye fitted with rigid lenses, the increased blink rate dropped to values similar to that before lens insertion and the open palpebral aperture returned to baseline values, suggesting that corneal and/or lid margin sensitivity was mediating the increased blink rate and narrowed palpebral aperture. We also investigated the changes in the blink rate and completeness with soft contact lenses including a soft sphere, double slab-off toric design and periballast toric design. Soft contact lenses did not cause any significant changes in the blink rate, closed palpebral aperture, open palpebral aperture and the percentage of incomplete blinks in either primary gaze or downward gaze. After applying anaesthetic eye drops, the blink rate reduced in both primary gaze and downward gaze, however this difference was not statistically significant. The size of the closed palpebral aperture and open palpebral aperture did not show any significant changes after applying anaesthetic eye drops. However it should be noted that the effects of rigid and soft contact lenses that we observed in these studies were only the immediate reaction to contact lenses and in the longer term, it is likely that these responses will vary as the eye adapts to the presence of the lenses.

Arterial travel time estimation : revisiting the classical procedure

Travel time is an important network performance measure and it quantifies congestion in a manner easily understood by all transport users. In urban networks, travel time estimation is challenging due to number of reasons such as, fluctuations in traffic flow due to traffic signals, significant flow to/from mid link sinks/sources, etc. The classical analytical procedure utilizes cumulative plots at upstream and downstream locations for estimating travel time between the two locations. In this paper, we discuss about the issues and challenges with classical analytical procedure such as its vulnerability to non conservation of flow between the two locations. The complexity with respect to exit movement specific travel time is discussed. Recently, we have developed a methodology utilising classical procedure to estimate average travel time and its statistic on urban links (Bhaskar, Chung et al. 2010). Where, detector, signal and probe vehicle data is fused. In this paper we extend the methodology for route travel time estimation and test its performance using simulation. The originality is defining cumulative plots for each exit turning movement utilising historical database which is self updated after each estimation. The performance is also compared with a method solely based on probe (Probe-only). The performance of the proposed methodology has been found insensitive to different route flow, with average accuracy of more than 94% given a probe per estimation interval which is more than 5% increment in accuracy with respect to Probe-only method.

The effects of the 2009 dust storm on emergency admissions to a hospital in Brisbane, Australia

In September 2009 an enormous dust storm swept across eastern Australia. Dust is potentially hazardous to health as it interferes with breathing, and previous dust storms have been linked to increased risks of asthma and even death. We examined whether the 2009 Australian dust storm changed the volume or characteristics of emergency admissions to hospital. We used an observational study design, using time series analyses to examine changes in the number of admissions, and case-only analyses to examine changes in the characteristics of admissions. The admission data were from the Prince Charles Hospital, Brisbane, between 1 January 2009 and 31 October 2009. There was a 39% increase in emergency admissions associated with the storm (95% confidence interval: 5, 81%), which lasted for just one day. The health effects of the storm could not be detected using particulate matter levels. We found no significant change in the characteristics of admissions during the storm, specifically there was no increase in respiratory admissions. The dust storm had a short-lived impact on emergency hospital admissions. This may be because the public took effective avoidance measures, or because the dust was simply not toxic, being mainly composed of soil. Emergency departments should be prepared for a short-term increase in admissions during dust storms.

Telemonitoring or Structured Telephone Support Programmes for Patients with Chronic Heart Failure: Systematic Review and Meta-Analysis

Objective: To determine whether remote monitoring (structured telephone support or telemonitoring) without regular clinic or home visits improves outcomes for patients with chronic heart failure. Data sources: 15 electronic databases, hand searches of previous studies, and contact with authors and experts. Data extraction: Two investigators independently screened the results. Review methods: Published randomised controlled trials comparing remote monitoring programmes with usual care in patients with chronic heart failure managed within the community. Results: 14 randomised controlled trials (4264 patients) of remote monitoring met the inclusion criteria: four evaluated telemonitoring, nine evaluated structured telephone support, and one evaluated both. Remote monitoring programmes reduced the rates of admission to hospital for chronic heart failure by 21% (95% confidence interval 11% to 31%) and all cause mortality by 20% (8% to 31%); of the six trials evaluating health related quality of life three reported significant benefits with remote monitoring, and of the four studies examining healthcare costs with structured telephone support three reported reduced cost and one no effect. Conclusion: Programmes for chronic heart failure that include remote monitoring have a positive effect on clinical outcomes in community dwelling patients with chronic heart failure.

Analysis for the use of cumulative plots for travel time estimation on signalized network

This paper provides fundamental understanding for the use of cumulative plots for travel time estimation on signalized urban networks. Analytical modeling is performed to generate cumulative plots based on the availability of data: a) Case-D, for detector data only; b) Case-DS, for detector data and signal timings; and c) Case-DSS, for detector data, signal timings and saturation flow rate. The empirical study and sensitivity analysis based on simulation experiments have observed the consistency in performance for Case-DS and Case-DSS, whereas, for Case-D the performance is inconsistent. Case-D is sensitive to detection interval and signal timings within the interval. When detection interval is integral multiple of signal cycle then it has low accuracy and low reliability. Whereas, for detection interval around 1.5 times signal cycle both accuracy and reliability are high.

Information interventions for orienting patients and their carers to cancer care facilities

Background: Cancer patients experience distress and anxiety related to their diagnosis, treatment and the unfamiliar cancer centre. Strategies with the aim of orienting patients to a cancer care facility may improve patient outcomes. Although meeting patients' information needs at different stages is important, there is little agreement about the type of information and the timing for information to be given. Orientation interventions aim to address information needs at the start of a person's experience with a cancer care facility. The extent of any benefit of these interventions is unknown. Objectives: To assess the effects of information interventions which orient patients and their carers/family to a cancer care facility, and to the services available in the facility. Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2); MEDLINE (OvidSP) (1966 to Jun 2011), EMBASE (Ovid SP) (1966 to Jun 2011), CINAHL (EBSCO) (1982 to Jun 2011), PsycINFO (OvidSP) (1966 to Jun 2011), review articles and reference lists of relevant articles. We contacted principal investigators and experts in the field. Selection Criteria: Randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs evaluating the effects of information interventions that orient patients and their carers/family to a cancer care facility. Data collection and analysis: Results of searches were reviewed against the pre-determined criteria for inclusion by two review authors. The primary outcomes were knowledge and understanding; health status and wellbeing, evaluation of care, and harms. Secondary outcomes were communication, skills acquisition, behavioural outcomes, service delivery, and health professional outcomes. We pooled results of RCTs using mean differences (MD) and 95% confidence intervals (CI). Main results: We included four RCTs involving 610 participants. All four trials aimed to investigate the effects of orientation programs for cancer patients to a cancer facility. There was high risk of bias across studies. Findings from two of the RCTs demonstrated significant benefits of the orientation intervention in relation to levels of distress (mean difference (MD) -8.96 (95% confidence interval (CI) -11.79 to -6.13), but non-significant benefits in relation to state anxiety levels (MD -9.77 (95% CI -24.96 to 5.41). Other outcomes for participants were generally positive (e.g. more knowledgeable about the cancer centre and cancer therapy, better coping abilities). No harms or adverse effects were measured or reported by any of the included studies. There were insufficient data on the other outcomes of interest. Authors conclusion: This review has demonstrated the feasibility and some potential benefits of orientation interventions. There was a low level of evidence suggesting that orientation interventions can reduce distress in patients. However, most of the other outcomes remain inconclusive (patient knowledge recall/ satisfaction). The majority of studies were subject to high risk of bias, and were likely to be insufficiently powered. Further well conducted and powered RCTs are required to provide evidence for determining the most appropriate intensity, nature, mode and resources for such interventions. Patient and carer-focused outcomes should be included.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

A Bayesian analysis of an agricultural field trial with three spatial dimensions

Modern technology now has the ability to generate large datasets over space and time. Such data typically exhibit high autocorrelations over all dimensions. The field trial data motivating the methods of this paper were collected to examine the behaviour of traditional cropping and to determine a cropping system which could maximise water use for grain production while minimising leakage below the crop root zone. They consist of moisture measurements made at 15 depths across 3 rows and 18 columns, in the lattice framework of an agricultural field. Bayesian conditional autoregressive (CAR) models are used to account for local site correlations. Conditional autoregressive models have not been widely used in analyses of agricultural data. This paper serves to illustrate the usefulness of these models in this field, along with the ease of implementation in WinBUGS, a freely available software package. The innovation is the fitting of separate conditional autoregressive models for each depth layer, the ‘layered CAR model’, while simultaneously estimating depth profile functions for each site treatment. Modelling interest also lay in how best to model the treatment effect depth profiles, and in the choice of neighbourhood structure for the spatial autocorrelation model. The favoured model fitted the treatment effects as splines over depth, and treated depth, the basis for the regression model, as measured with error, while fitting CAR neighbourhood models by depth layer. It is hierarchical, with separate onditional autoregressive spatial variance components at each depth, and the fixed terms which involve an errors-in-measurement model treat depth errors as interval-censored measurement error. The Bayesian framework permits transparent specification and easy comparison of the various complex models compared.

Towards improving mission execution for autonomous gliders with an ocean model and Kalman filter

In this paper, we examine the use of a Kalman filter to aid in the mission planning process for autonomous gliders. Given a set of waypoints defining the planned mission and a prediction of the ocean currents from a regional ocean model, we present an approach to determine the best, constant, time interval at which the glider should surface to maintain a prescribed tracking error, and minimizing time on the ocean surface. We assume basic parameters for the execution of a given mission, and provide the results of the Kalman filter mission planning approach. These results are compared with previous executions of the given mission scenario.

No evidence for subliminal affective priming with emotional facial expression primes

The present study investigated whether facial expressions of emotion presented outside consciousness awareness will elicit evaluative responses as assessed in affective priming. Participants were asked to evaluate pleasant and unpleasant target words that were preceded by masked or unmasked schematic (Experiment 1) or photographic faces (Experiments 1 and 2) with happy or angry expressions. They were either required to perform the target evaluation only or to perform the target evaluation and to name the emotion expressed by the face prime. Prime-target interval was 300 ms in Experiment 1 and 80 ms in Experiment 2. Naming performance confirmed the effectiveness of the masking procedure. Affective priming was evident after unmasked primes in tasks that required naming of the facial expressions for schematic and photographic faces and after unmasked primes in tasks that did not require naming for photographic faces. No affective priming was found after masked primes. The present study failed to provide evidence for affective priming with masked face primes, however, it indicates that voluntary attention to the primes enhances affective priming.

Visual backward masking performance in young adult emmetropes and myopes

Purpose. To investigate how temporal processing is altered in myopia and during myopic progression. Methods. In backward visual masking, a target's visibility is reduced by a mask presented quickly after the target. Thirty emmetropes, 40 low myopes, and 22 high myopes aged 18 to 26 years completed location and resolution masking tasks. The location task examined the ability to detect letters with low contrast and large stimulus size. The resolution task involved identifying a small letter and tested resolution and color discrimination. Target and mask stimuli were presented at nine short interstimulus intervals (12 to 259 ms) and at 1000 ms (long interstimulus interval condition). Results. In comparison with emmetropes, myopes had reduced ability in both locating and identifying briefly presented stimuli but were more affected by backward masking for a low contrast location task than for a resolution task. Performances of low and high myopes, as well as stable and progressing myopes, were similar for both masking tasks. Task performance was not correlated with myopia magnitude. Conclusions. Myopes were more affected than emmetropes by masking stimuli for the location task. This was not affected by magnitude or progression rate of myopia, suggesting that myopes have the propensity for poor performance in locating briefly presented low contrast objects at an early stage of myopia development.

A systematic review : the effects of orientation programs for cancer patients and their family/carers

Objectives To assess the effects of information interventions which orient patients and their carers/family to a cancer care facility and the services available within the facility. Design Systematic review of randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs. Data sources MEDLINE, CINAHL, PsycINFO, EMBASE and the Cochrane Central Register of Controlled Trials. Methods We included studies evaluating the effect of an orientation intervention, compared with a control group which received usual care, or with trials comparing one orientation intervention with another orientation intervention. Results Four RCTs of 610 participants met the criteria for inclusion. Findings from two RCTs demonstrated significant benefits of the orientation intervention in relation to reduced levels of distress (mean difference (MD): −8.96, 95% confidence interval (95%CI): −11.79 to −6.13), but non-significant benefits in relation to the levels state anxiety levels (MD −9.77) (95%CI: −24.96 to 5.41). There are insufficient data on the other outcomes of interest. Conclusions This review has demonstrated the feasibility and some potential benefits of orientation interventions. There was a low level of evidence to suggest that orientation interventions can reduce distress in patients. However, other outcomes, including patient knowledge recall/satisfaction, remain inconclusive. The majority of trials were subjected to high risk of bias and were likely to be insufficiently powered. Further well conducted and powered RCTs are required to provide evidence for determining the most appropriate intensity, nature, mode and resources for such interventions. Patient and carer-focused outcomes should be included.

The effect of exercise intensity on fat oxidation and non-exercise activity thermogenesis in overweight/obese men

It is frequently reported that the actual weight loss achieved through exercise interventions is less than theoretically expected. Amongst other compensatory adjustments that accompany exercise training (e.g., increases in resting metabolic rate and energy intake), a possible cause of the less than expected weight loss is a failure to produce a marked increase in total daily energy expenditure due to a compensatory reduction in non-exercise activity thermogenesis (NEAT). Therefore, there is a need to understand how behaviour is modified in response to exercise interventions. The proposed benefits of exercise training are numerous, including changes to fat oxidation. Given that a diminished capacity to oxidise fat could be a factor in the aetiology of obesity, an exercise training intensity that optimises fat oxidation in overweight/obese individuals would improve impaired fat oxidation, and potentially reduce health risks that are associated with obesity. To improve our understanding of the effectiveness of exercise for weight management, it is important to ensure exercise intensity is appropriately prescribed, and to identify and monitor potential compensatory behavioural changes consequent to exercise training. In line with the gaps in the literature, three studies were performed. The aim of Study 1 was to determine the effect of acute bouts of moderate- and high-intensity walking exercise on NEAT in overweight and obese men. Sixteen participants performed a single bout of either moderate-intensity walking exercise (MIE) or high-intensity walking exercise (HIE) on two separate occasions. The MIE consisted of walking for 60-min on a motorised treadmill at 6 km.h-1. The 60-min HIE session consisted of walking in 5-min intervals at 6 km.h-1 and 10% grade followed by 5-min at 0% grade. NEAT was assessed by accelerometer three days before, on the day of, and three days after the exercise sessions. There was no significant difference in NEAT vector magnitude (counts.min-1) between the pre-exercise period (days 1-3) and the exercise day (day 4) for either protocol. In addition, there was no change in NEAT during the three days following the MIE session, however NEAT increased by 16% on day 7 (post-exercise) compared with the exercise day (P = 0.32). During the post-exercise period following the HIE session, NEAT was increased by 25% on day 7 compared with the exercise day (P = 0.08), and by 30-33% compared with the pre-exercise period (day 1, day 2 and day 3); P = 0.03, 0.03, 0.02, respectively. To conclude, a single bout of either MIE or HIE did not alter NEAT on the exercise day or on the first two days following the exercise session. However, extending the monitoring of NEAT allowed the detection of a 48 hour delay in increased NEAT after performing HIE. A longer-term intervention is needed to determine the effect of accumulated exercise sessions over a week on NEAT. In Study 2, there were two primary aims. The first aim was to test the reliability of a discontinuous incremental exercise protocol (DISCON-FATmax) to identify the workload at which fat oxidation is maximised (FATmax). Ten overweight and obese sedentary male men (mean BMI of 29.5 ¡Ó 4.5 kg/m2 and mean age of 28.0 ¡Ó 5.3 y) participated in this study and performed two identical DISCON-FATmax tests one week apart. Each test consisted of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The starting work load of 28 W was increased every 4-min using 14 W increments followed by 2-min rest intervals. When the respiratory exchange ratio was consistently >1.0, the workload was increased by 14 W every 2-min until volitional exhaustion. Fat oxidation was measured by indirect calorimetry. The mean FATmax, ƒtV O2peak, %ƒtV O2peak and %Wmax at which FATmax occurred during the two tests were 0.23 ¡Ó 0.09 and 0.18 ¡Ó 0.08 (g.min-1); 29.7 ¡Ó 7.8 and 28.3 ¡Ó 7.5 (ml.kg-1.min-1); 42.3 ¡Ó 7.2 and 42.6 ¡Ó 10.2 (%ƒtV O2max) and 36.4 ¡Ó 8.5 and 35.4 ¡Ó 10.9 (%), respectively. A paired-samples T-test revealed a significant difference in FATmax (g.min-1) between the tests (t = 2.65, P = 0.03). The mean difference in FATmax was 0.05 (g.min-1) with the 95% confidence interval ranging from 0.01 to 0.18. Paired-samples T-test, however, revealed no significant difference in the workloads (i.e. W) between the tests, t (9) = 0.70, P = 0.4. The intra-class correlation coefficient for FATmax (g.min-1) between the tests was 0.84 (95% confidence interval: 0.36-0.96, P < 0.01). However, Bland-Altman analysis revealed a large disagreement in FATmax (g.min-1) related to W between the two tests; 11 ¡Ó 14 (W) (4.1 ¡Ó 5.3 ƒtV O2peak (%)).These data demonstrate two important phenomena associated with exercise-induced substrate oxidation; firstly, that maximal fat oxidation derived from a discontinuous FATmax protocol differed statistically between repeated tests, and secondly, there was large variability in the workload corresponding with FATmax. The second aim of Study 2 was to test the validity of a DISCON-FATmax protocol by comparing maximal fat oxidation (g.min-1) determined by DISCON-FATmax with fat oxidation (g.min-1) during a continuous exercise protocol using a constant load (CONEX). Ten overweight and obese sedentary males (BMI = 29.5 ¡Ó 4.5 kg/m2; age = 28.0 ¡Ó 4.5 y) with a ƒtV O2max of 29.1 ¡Ó 7.5 ml.kg-1.min-1 performed a DISCON-FATmax test consisting of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The 1-h CONEX protocol used the workload from the DISCON-FATmax to determine FATmax. The mean FATmax, ƒtV O2max, %ƒtV O2max and workload at which FATmax occurred during the DISCON-FATmax were 0.23 ¡Ó 0.09 (g.min-1); 29.1 ¡Ó 7.5 (ml.kg-1.min-1); 43.8 ¡Ó 7.3 (%ƒtV O2max) and 58.8 ¡Ó 19.6 (W), respectively. The mean fat oxidation during the 1-h CONEX protocol was 0.19 ¡Ó 0.07 (g.min-1). A paired-samples T-test revealed no significant difference in fat oxidation (g.min-1) between DISCON-FATmax and CONEX, t (9) = 1.85, P = 0.097 (two-tailed). There was also no significant correlation in fat oxidation between the DISCON-FATmax and CONEX (R=0.51, P = 0.14). Bland- Altman analysis revealed a large disagreement in fat oxidation between the DISCONFATmax and CONEX; the upper limit of agreement was 0.13 (g.min-1) and the lower limit of agreement was ¡V0.03 (g.min-1). These data suggest that the CONEX and DISCONFATmax protocols did not elicit different rates of fat oxidation (g.min-1). However, the individual variability in fat oxidation was large, particularly in the DISCON-FATmax test. Further research is needed to ascertain the validity of graded exercise tests for predicting fat oxidation during constant load exercise sessions. The aim of Study 3 was to compare the impact of two different intensities of four weeks of exercise training on fat oxidation, NEAT, and appetite in overweight and obese men. Using a cross-over design 11 participants (BMI = 29 ¡Ó 4 kg/m2; age = 27 ¡Ó 4 y) participated in a training study and were randomly assigned initially to: [1] a lowintensity (45%ƒtV O2max) exercise (LIT) or [2] a high-intensity interval (alternate 30 s at 90%ƒtV O2max followed by 30 s rest) exercise (HIIT) 40-min duration, three times a week. Participants completed four weeks of supervised training and between cross-over had a two week washout period. At baseline and the end of each exercise intervention,ƒtV O2max, fat oxidation, and NEAT were measured. Fat oxidation was determined during a standard 30-min continuous exercise bout at 45%ƒtV O2max. During the steady state exercise expired gases were measured intermittently for 5-min periods and HR was monitored continuously. In each training period, NEAT was measured for seven consecutive days using an accelerometer (RT3) the week before, at week 3 and the week after training. Subjective appetite sensations and food preferences were measured immediately before and after the first exercise session every week for four weeks during both LIT and HIIT. The mean fat oxidation rate during the standard continuous exercise bout at baseline for both LIT and HIIT was 0.14 ¡Ó 0.08 (g.min-1). After four weeks of exercise training, the mean fat oxidation was 0.178 ¡Ó 0.04 and 0.183 ¡Ó 0.04 g.min-1 for LIT and HIIT, respectively. The mean NEAT (counts.min-1) was 45 ¡Ó 18 at baseline, 55 ¡Ó 22 and 44 ¡Ó 16 during training, and 51 ¡Ó 14 and 50 ¡Ó 21 after training for LIT and HIIT, respectively. There was no significant difference in fat oxidation between LIT and HIIT. Moreover, although not statistically significant, there was some evidence to suggest that LIT and HIIT tend to increase fat oxidation during exercise at 45% ƒtV O2max (P = 0.14 and 0.08, respectively). The order of training treatment did not significantly influence changes in fat oxidation, NEAT, and appetite. NEAT (counts.min-1) was not significantly different in the week following training for either LIT or HIIT. Although not statistically significant (P = 0.08), NEAT was 20% lower during week 3 of exercise training in HIIT compared with LIT. Examination of appetite sensations revealed differences in the intensity of hunger, with higher ratings after LIT compared with HIIT. No differences were found in preferences for high-fat sweet foods between LIT and HIIT. In conclusion, the results of this thesis suggest that while fat oxidation during steady state exercise was not affected by the level of exercise intensity, there is strong evidence to suggest that intense exercise could have a debilitative effect on NEAT.