Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation

BACKGROUND: Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation. METHODS: This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura. RESULTS: Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant. CONCLUSION: This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.

A flexible Bayesian model for describing temporal variability of N2O emissions from an Australian pasture

Soil-based emissions of nitrous oxide (N2O), a well-known greenhouse gas, have been associated with changes in soil water-filled pore space (WFPS) and soil temperature in many previous studies. However, it is acknowledged that the environment-N2O relationship is complex and still relatively poorly unknown. In this article, we employed a Bayesian model selection approach (Reversible jump Markov chain Monte Carlo) to develop a data-informed model of the relationship between daily N2O emissions and daily WFPS and soil temperature measurements between March 2007 and February 2009 from a soil under pasture in Queensland, Australia, taking seasonal factors and time-lagged effects into account. The model indicates a very strong relationship between a hybrid seasonal structure and daily N2O emission, with the latter substantially increased in summer. Given the other variables in the model, daily soil WFPS, lagged by a week, had a negative influence on daily N2O; there was evidence of a nonlinear positive relationship between daily soil WFPS and daily N2O emission; and daily soil temperature tended to have a linear positive relationship with daily N2O emission when daily soil temperature was above a threshold of approximately 19°C. We suggest that this flexible Bayesian modeling approach could facilitate greater understanding of the shape of the covariate-N2O flux relation and detection of effect thresholds in the natural temporal variation of environmental variables on N2O emission.

Princess Alexandra Hospital model of comprehensive geriatric assessment of cancer patients : methodological and logistical aspects

There is increasing momentum in cancer care to implement a two stage assessment process that accurately determines the ability of older patients to cope with, and benefit from, chemotherapy. The two-step approach aims to ensure that patients clearly fit for chemotherapy can be accurately identified and referred for treatment without undergoing a time- and resource-intensive comprehensive geriatric assessment (CGA). Ideally, this process removes the uncertainty of how to classify and then appropriately treat the older cancer patient. After trialling a two-stage screen and CGA process in the Division of Cancer Services at Princess Alexandra Hospital (PAH) in 2011-2012, we implemented a model of oncogeriatric care based on our findings. In this paper, we explore the methodological and practical aspects of implementing the PAH model and outline further work needed to refine the process in our treatment context.

Are target date funds the easy bake option?

Target date funds provide a simple, automated approach to retirement savings in defined contribution plans. The passing of the Pension Protection Act of 2006 has seen an increase in the popularity of these funds in the United States, becoming the default option for many plans. However, recent research findings have challenged the easy bake or ‘set-and-forget’ nature of target date funds. This study explores some of the critical design features of target date funds (which shifts an individual’s asset allocation from growth to defensive assets following a pre-set glidepath) against a simple balanced (or target risk) fund design. Using both time-weighted and dollar-weighted returns, our results suggest that there is more to achieving successful retirement outcomes than the investor simply selecting a proposed year of retirement. Our findings can perhaps be summarized by Einstein’s famous epithet, that in the murky world of retirement product design, everything should be made as simple as possible, but not simpler.

Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (VO2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of L-[ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ?4-fold in LOW (P < 0.01) and ?11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.

Pseudo plastic zone analysis of steel frame structures comprising non-compact sections

Application of `advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A concentrated plasticity method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in this paper. The pseudo plastic zone method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established by comparison with a comprehensive range of analytical benchmark frame solutions. The pseudo plastic zone method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Ensuring sessional academic success by rethinking the place of academic development

There has been growing recognition of the contribution that Sessional Academics make to student learning in higher education; with recent studies concluding that around half Australian university teaching is now performed by casual staff [Red Report 2008; May, 2013]. However, sector-wide research and institutional audits continue to raise concerns about academic development and quality assurance, as well as the recognition and retention of Sessional Academics. In response, universities offer academic development programs. However, while such centrally offered programs are undoubtedly useful, they are necessarily generic and cannot address the local contexts of faculties or provide ‘on the ground’ support. This paper presents a new, distributed model of academic support and development for Sessional academics at Queensland University of Technology. Entitled the Sessional Academic Success program, it employs the principles of distributed leadership. Experienced Sessional academics are trained and supported to assume roles as Sessional Academic Success Advisors within their schools. Complementing our central programs, they design bespoke, locally situated, peer-to-peer academic development for new Sessional teachers; provide ‘just in time’, safe and reliable advice; and build supportive communities of teaching practice in their local contexts. This distributed model re-envisages the forms and places of academic development and support. It helps ensure that new Sessional Academics are embraced by faculty life. And, recognizing that experienced Sessional Academics have much to contribute to the advancement of learning and teaching, it builds their capacity through leadership opportunities. As the designer/facilitator of the program and a Sessional Academic Success Advisor, the authors take a dialogic approach and together describe the design, implementation and outcomes of the program.

Literacies on the Web : Co-Production of Literary Texts on Fan Fiction Sites

In this chapter the authors discuss and informal learning settings such as fan fiction sites and their relations to teaching and learning within formal learning settings. Young people today spend a lot of time with social media built on user generated content. These media are often characterized by participatory culture which offers a good environment for developing skills and identity work. In this chapter the authors problematize fan fiction sites as informal learning settings where the possibilities to learn are powerful and significant. They also discuss the learning processes connected to the development of literacies. Here the rhetoric principle of “imitatio” plays a vital part as well as the co-production of texts on the sites, strongly supported by the beta reader and the power of positive feedback. They also display that some fans, through the online publication of fan fiction, are able to develop their craft in a way which previously have been impossible.

Port-Hamiltonian theory of motion control for marine craft

Port-Hamiltonian Systems (PHS) have a particular form that incorporates explicitly a function of the total energy in the system (energy function) and also other functions that describe structure of the system in terms of energy distribution. For PHS, the product of the input and output variables gives the rate of energy change. This type of systems have the property that under certain conditions on the energy function, the system is passive; and thus, stable. Therefore, if one can design a controller such that the closed-loop system retains - or takes - a PHS form, such closed-loop system will inherit the properties of passivity and stability. In this paper, the classical model of marine craft is put into a PHS form. It is shown that models used for positioning control do not have a PHS form due to a kinematic transformation, but a control design can be done such that the closed-loop system takes a PHS form. It is further shown how integral action can be added and how the PHS-form can be exploited to provide a procedure for control design that ensures passivity and thus stability.

Comparison of accelerometer cut points for predicting activity intensity in youth

The absence of comparative validity studies has prevented researchers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents. PURPOSE This study aimed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure, measured by indirect calorimetry, as a criterion reference standard. METHODS A total of 206 participants between the ages of 5 and 15 yr completed 12 standardized activity trials. Trials consisted of sedentary activities (lying down, writing, computer game), lifestyle activities (sweeping, laundry, throw and catch, aerobics, basketball), and ambulatory activities (comfortable walk, brisk walk, brisk treadmill walk, running). During each trial, participants wore an ActiGraph GT1M, and VO 2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system. Physical activity intensity was estimated using five independently developed cut points: Freedson/Trost (FT), Puyau (PU), Treuth (TR), Mattocks (MT), and Evenson (EV). Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve (ROC-AUC). RESULTS Across all four intensity levels, the EV (κ = 0.68) and FT (κ = 0.66) cut points exhibited significantly better agreement than TR (κ = 0.62), MT (κ = 0.54), and PU (κ = 0.36). The EV and FT cut points exhibited significantly better classification accuracy for moderate-to vigorous-intensity physical activity (ROC-AUC = 0.90) than TR, PU, or MT cut points (ROC-AUC = 0.77-0.85). Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages. The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy (ROC-AUC = 0.90). CONCLUSIONS On the basis of these findings, we recommend that researchers use the EV ActiGraph cut points to estimate time spent in sedentary, light-, moderate-, and vigorous-intensity activity in children and adolescents. Copyright © 2011 by the American College of Sports Medicine.

Beliefs about infant regulation, early infant behaviors and maternal postnatal depressive symptoms

Background: Young infants may have irregular sleeping and feeding patterns. Such regulation difficulties are known correlates of maternal depressive symptoms. Parental beliefs regarding their role in regulating infant behaviours also may play a role. We investigated the association of depressive symptoms with infant feeding/sleeping behaviours, parent regulation beliefs, and the interaction of the two. Method: In 2006, 272 mothers of infants aged up to 24 weeks completed a questionnaire about infant behaviour and regulation beliefs. Participants were recruited from general medical practices and child health clinics in Brisbane, Australia. Depressive symptomology was measured using the Edinburgh Postnatal Depression Scale (EPDS). Other measures were adapted from the ALSPAC study. Results: Regression analyses were run controlling for partner support, other support, life events, and a range of demographic variables. Maternal depressive symptoms were associated with infant sleeping and feeding problems but not regulation beliefs. The most important infant predictor was sleep behaviours with feeding behaviours accounting for little additional variance. An interaction between regulation beliefs and sleep behaviours was found. Mothers with high regulation beliefs were more susceptible to postnatal depressive symptoms when infant sleep behaviours were problematic. Conclusion: Mothers of young infants who expect greater control are more susceptible to depressive symptoms when their infant presents challenging sleep behaviour.

Blood transfer devices for malaria rapid diagnostic tests : evaluation of accuracy, safety and ease of use

Background: Malaria rapid diagnostic tests (RDTs) are increasingly used by remote health personnel with minimal training in laboratory techniques. RDTs must, therefore, be as simple, safe and reliable as possible. Transfer of blood from the patient to the RDT is critical to safety and accuracy, and poses a significant challenge to many users. Blood transfer devices were evaluated for accuracy and precision of volume transferred, safety and ease of use, to identify the most appropriate devices for use with RDTs in routine clinical care. Methods: Five devices, a loop, straw-pipette, calibrated pipette, glass capillary tube, and a new inverted cup device, were evaluated in Nigeria, the Philippines and Uganda. The 227 participating health workers used each device to transfer blood from a simulated finger-prick site to filter paper. For each transfer, the number of attempts required to collect and deposit blood and any spilling of blood during transfer were recorded. Perceptions of ease of use and safety of each device were recorded for each participant. Blood volume transferred was calculated from the area of blood spots deposited on filter paper. Results: The overall mean volumes transferred by devices differed significantly from the target volume of 5 microliters (p < 0.001). The inverted cup (4.6 microliters) most closely approximated the target volume. The glass capillary was excluded from volume analysis as the estimation method used is not compatible with this device. The calibrated pipette accounted for the largest proportion of blood exposures (23/225, 10%); exposures ranged from 2% to 6% for the other four devices. The inverted cup was considered easiest to use in blood collection (206/ 226, 91%); the straw-pipette and calibrated pipette were rated lowest (143/225 [64%] and 135/225 [60%] respectively). Overall, the inverted cup was the most preferred device (72%, 163/227), followed by the loop (61%, 138/227). Conclusions: The performance of blood transfer devices varied in this evaluation of accuracy, blood safety, ease of use, and user preference. The inverted cup design achieved the highest overall performance, while the loop also performed well. These findings have relevance for any point-of-care diagnostics that require blood sampling.