Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Individual variability in compensatory eating following acute exercise in overweight and obese women

Background While compensatory eating following acute aerobic exercise is highly variable, little is known about the underling mechanisms that contribute to alterations in exercise-induced eating behaviour. Methods Overweight and obese women (BMI = 29.6 ± 4.0kg.m2) performed a bout of cycling individually tailored to expend 400kcal (EX), or a time-matched no exercise control condition in a randomised, counter-balanced order. Sixty minutes after the cessation of exercise, an ad libitum test meal was provided. Substrate oxidation and subjective appetite ratings were measured during exercise/time-matched rest, and during the period between the cessation of exercise and food consumption. Results While ad libitum EI did not differ between EX and the control condition (666.0 ± 203.9kcal vs. 664.6 ± 174.4kcal, respectively; ns), there was marked individual variability in compensatory energy intake (EI). The difference in EI between EX and the control condition ranged from -234.3 to +278.5kcal. Carbohydrate oxidation during exercise was positively associated with post-exercise EI, accounting for 37% of the variance in EI (r = 0.57; p = 0.02). Conclusions These data indicate that capacity of acute exercise to create a short-term energy deficit in overweight and obese women is highly variable. Furthermore, exercise-induced CHO oxidation can explain part of the variability in acute exercise-induced compensatory eating. Post-exercise compensatory eating could serve as an adaptive response to facilitate the restoration of carbohydrate balance.

Cardiac parasympathetic reactivation following exercise : implications for training prescription

The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0–90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1–48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24–48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.

Exercising QS: Quantitative skills in an exercise science course

This study seeks to bring the discipline of exercise science into the discussion of Quantitative Skills (QS) in Science. The author’s experiences of providing learning support to students and working with educators in the field are described, demonstrating the difficulty of encouraging students to address their skills deficit. A survey of students’ perceptions of their own QS and of that required for their course, demonstrates the difficulties faced by students who do not have the prescribed assumed knowledge for the course. Limited results from academics suggest that their perceptions of students’ QS deficits are even more dire than those of the under-prepared students.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults (Protocol)

"This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects (benefits and harms) of whole-body cryotherapy (cold air exposure) for preventing and treating muscle soreness after exercise in adults." -- publisher website

Testing the psychometric properties of the Brisbane Practice Environment Measure using Exploratory Factor Analysis and Confirmatory Factor Analysis in an Australian registered nurse population

A cross-sectional survey was conducted, and the construct validity and reliability of the Brisbane Practice Environment Measure in an Australian sample of registered nurses were examined. Nurses were randomly selected from the database of an Australian nursing organization. The original 33 items of the Brisbane Practice Environment Measure were utilized to inform the psychometric properties using confirmatory factor analysis. The Cronbach's alpha was 0.938 for the total scale and ranged 0.657–0.887 for the subscales. A five-factor structure of the measure was confirmed, χ2 = 944.622, (P < 0.01), χ2/d.f. ratio = 2.845, Tucker Lewis Index 0.929, Root Mean Square Error = 0.061 and Comparative Fit Index = 0.906. The selected 28 items of the measure proved reliable and valid in measuring effects of the practice environment upon Australian nurses. The implications are that regular measurement of the practice environment using these 28 items might assist in the development of strategies which might improve job satisfaction and retention of registered nurses in Australia.

The "caring experience": testing the psychometric properties of the Caring Efficacy Scale

The purpose of the study was to undertake rigorous psychometric testing of the Caring Efficacy Scale in a sample of Registered Nurses. A cross-sectional survey of 2000 registered nurses was undertaken. The Caring Efficacy Scale was utilised to inform the psychometric properties of the selected items of the Caring Efficacy Scale. Cronbach’s Alpha identified reliability of the data. Exploratory Factor Analysis and Confirmatory Factor Analysis were undertaken to validate the factors. Confirmatory factor analysis confirmed the development of two factors; Confidence to Care and Doubts and Concerns. The Caring Efficacy Scale has undergone rigorous psychometric testing, affording evidence of internal consistency and goodness-of-fit indices within satisfactory ranges. The Caring Efficacy Scale is valid for use in an Australian population of registered nurses. The scale can be used as a subscale or total score reflective of self-efficacy in nursing. This scale may assist nursing educators to predict levels of caring efficacy.

Interactions between cars and motorcycles testing underlying concepts through integration of on-road and simulator studies

We conducted on-road and simulator studies to explore the mechanisms underpinning driver-rider crashes. In Study 1 the verbal protocols of 40 drivers and riders were assessed at intersections as part of a 15km on-road route in Melbourne. Network analysis of the verbal transcripts highlighted key differences in the situation awareness of drivers and riders at intersections. In a further study using a driving simulator we examined in car drivers the influence of acute exposure to motorcyclists. In a 15 min simulated drive, 40 drivers saw either no motorcycles or a high number of motorcycles in the surrounding traffic. In a subsequent 45-60 min drive, drivers were asked to detect motorcycles in traffic. The proportion of motorcycles was manipulated so that there was either a high (120) or low (6) number of motorcycles during the drive. Those drivers exposed to a high number of motorcycles were significantly faster at detecting motorcycles. Fundamentally, the incompatible situation awareness at intersections by drivers and riders underpins the conflicts. Study 2 offers some suggestion for a countermeasure here, although more research around schema and exposure training to support safer interactions is needed.

Library Research Support in developing, testing and promoting an open cyberinfrastructure

QUT Library continues to rethink research support with eResearch as a primary driver. The support to the development of the Lens, an open global cyberinfrastructure, has been especially important in the light of technology transfer promotion, and partly in the response to researchers’ needs in following the innovation landscapes not only within the scientific but also patent literature. The Lens http://www.lens.org/lens/ project makes innovation more efficient, fair, transparent and inclusive. It is a joint effort between Cambia http://www.cambia.org.au and Queensland University of Technology (QUT). The Lens serves more than 84 million patent documents in the world as open, annotatable digital public goods that are integrated with scholarly and technical literature along with regulatory and business data. Users can link from search results to visualization and document clusters; from a patent document description to its full-text; from there, if applicable, the sequence data can also be found. Figure 1 shows a BLAST Alignment (DNA) using the Lens. A unique feature of the Lens is the ability to embed search and BLAST results into blogs and websites, and provide real-time updates to them. PatSeq Explorer http://www.lens.org/lens/bio/patseqexplorer allows users to navigate patent sequences that map onto the human genome and in the future, many other genomes. PatSeq Explorer offers three level views for the sequence information and links each group of sequences at the chromosomal level to their corresponding patent documents in the Lens. By integrating sequence and patent search and document clustering capabilities, users can now understand the big and small details on the true extent and scope of genetic sequence patents. QUT Library supported Cambia in developing, testing and promoting the Lens. This poster demonstrates QUT Library’s provision of best practice and holistic research support to a research group and how QUT Librarians have acquired new capabilities to meet the needs of the researchers beyond traditional research support practices.

Neuromuscular hamstring function in response to intermittent running and previous injury

This thesis examined the impact of previous hamstring injury and fatigue on the function of the hamstring muscles and their neural control. The work established the role of neuromuscular inhibition after hamstring injury and involved the development of a new field testing device for eccentric hamstring strength, which is now in high demand in elite sport worldwide. David has four peer-reviewed publications from this doctoral work.

Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis

Quantity and timing of protein ingestion are major factors regulating myofibrillar protein synthesis (MPS). However, the effect of specific ingestion patterns on MPS throughout a 12 h period is unknown. We determined how different distributions of protein feeding during 12 h recovery after resistance exercise affects anabolic responses in skeletal muscle. Twenty-four healthy trained males were assigned to three groups (n = 8/group) and undertook a bout of resistance exercise followed by ingestion of 80 g of whey protein throughout 12 h recovery in one of the following protocols: 8 × 10 g every 1.5 h (PULSE); 4 × 20 g every 3 h (intermediate: INT); or 2 × 40 g every 6 h (BOLUS). Muscle biopsies were obtained at rest and after 1, 4, 6, 7 and 12 h post exercise. Resting and post-exercise MPS (l-[ring-(13)C6] phenylalanine), and muscle mRNA abundance and cell signalling were assessed. All ingestion protocols increased MPS above rest throughout 1-12 h recovery (88-148%, P < 0.02), but INT elicited greater MPS than PULSE and BOLUS (31-48%, P < 0.02). In general signalling showed a BOLUS>INT>PULSE hierarchy in magnitude of phosphorylation. MuRF-1 and SLC38A2 mRNA were differentially expressed with BOLUS. In conclusion, 20 g of whey protein consumed every 3 h was superior to either PULSE or BOLUS feeding patterns for stimulating MPS throughout the day. This study provides novel information on the effect of modulating the distribution of protein intake on anabolic responses in skeletal muscle and has the potential to maximize outcomes of resistance training for attaining peak muscle mass.

Random breath testing in Queensland and Western Australia : Examination of how the random breath testing rate influences alcohol related traffic crash rates

In this paper we explore the relationship between monthly random breath testing (RBT) rates (per 1000 licensed drivers) and alcohol-related traffic crash (ARTC) rates over time, across two Australian states: Queensland and Western Australia. We analyse the RBT, ARTC and licensed driver rates across 12 years; however, due to administrative restrictions, we model ARTC rates against RBT rates for the period July 2004 to June 2009. The Queensland data reveals that the monthly ARTC rate is almost flat over the five year period. Based on the results of the analysis, an average of 5.5 ARTCs per 100,000 licensed drivers are observed across the study period. For the same period, the monthly rate of RBTs per 1000 licensed drivers is observed to be decreasing across the study with the results of the analysis revealing no significant variations in the data. The comparison between Western Australia and Queensland shows that Queensland's ARTC monthly percent change (MPC) is 0.014 compared to the MPC of 0.47 for Western Australia. While Queensland maintains a relatively flat ARTC rate, the ARTC rate in Western Australia is increasing. Our analysis reveals an inverse relationship between ARTC RBT rates, that for every 10% increase in the percentage of RBTs to licensed driver there is a 0.15 decrease in the rate of ARTCs per 100,000 licenced drivers. Moreover, in Western Australia, if the 2011 ratio of 1:2 (RBTs to annual number of licensed drivers) were to double to a ratio of 1:1, we estimate the number of monthly ARTCs would reduce by approximately 15. Based on these findings we believe that as the number of RBTs conducted increases the number of drivers willing to risk being detected for drinking driving decreases, because the perceived risk of being detected is considered greater. This is turn results in the number of ARTCs diminishing. The results of this study provide an important evidence base for policy decisions for RBT operations.