A method to evaluate the response of the coronary circulation of perfused rat heart to adenosine

Exogenous adenosine causes a monophasic dilation of the coronary vessels in paced, perfused rat heart preparations. Because levels of endogenous adenosine in paced hearts may mask the presence of high potency adenosine receptors, we have developed a method to measure coronary vascular responses in a potassium-arrested heart. Hearts from adult male, Wistar rats were perfused at a constant flow rate of 10 mL/min in the nonrecirculating, Langendorff mode, using Krebs-Henseleit buffer. After 30 min, coronary perfusion pressure was 44 +/- 1 mmHg (mean +/- SEM). Hearts were then perfused with a modified Krebs-Henseleit buffer containing 35 mM potassium. Coronary perfusion pressure increased by 84 +/- 3 mmHg. Adenosine-induced reductions in coronary perfusion pressure were expressed as a percentage of the maximal increase in pressure produced by modified Krebs-Henseleit buffer from the equilibration level. A concentration-response curve for adenosine (n = 6) was biphasic and best described by the presence of two adenosine receptors, with negative log EC50 values of 8.8 +/- 0.3 and 4.3 +/- 0.1, representing 29 +/- 3 and 71 +/- 3%, respectively, of the observed response. Interstitial adenosine sampled by microdialysis during potassium arrest was 25% of the concentration found in paced hearts. Endogenous adenosine in nonarrested hearts may obscure the biphasic response of the coronary vessels to adenosine.

Creating good lives through computer games

In this chapter we aim to explore how videogames can lead to improvements in wellbeing. Following Keyes (2007) and Huppert and So (2012) we view wellbeing as a multidimensional concept with both hedonic and eudaimonic aspects. In this chapter we take a broad approach in terms of exploring the impact of videogames on the psychological, social, and physical components of wellbeing. We explore how videogames have been shown to have an impact in each of these domains. Although there is a great deal of evidence for the actual and potential positive impacts of videogames, there are many unanswered questions regarding the situations in which there is likely to be an impact of videogame play on wellbeing, as well as the aspects of wellbeing that are likely to be impacted by videogame play. We conclude the chapter by outlining the key questions for future research. Our focus in this chapter is on the positive influences of videogames. We do not explore research on contexts in which negative impacts are possible or subgroups for which videogames could cause harm. However, these questions are obviously important and we see balanced engagement with age-appropriate videogames as a key prerequisite for any of the wellbeing benefits discussed below.

Dual compressible hybrid quantum secret sharing schemes based on extended unitary operations

A crucial issue with hybrid quantum secret sharing schemes is the amount of data that is allocated to the participants. The smaller the amount of allocated data, the better the performance of a scheme. Moreover, quantum data is very hard and expensive to deal with, therefore, it is desirable to use as little quantum data as possible. To achieve this goal, we first construct extended unitary operations by the tensor product of n, n ≥ 2, basic unitary operations, and then by using those extended operations, we design two quantum secret sharing schemes. The resulting dual compressible hybrid quantum secret sharing schemes, in which classical data play a complementary role to quantum data, range from threshold to access structure. Compared with the existing hybrid quantum secret sharing schemes, our proposed schemes not only reduce the number of quantum participants, but also the number of particles and the size of classical shares. To be exact, the number of particles that are used to carry quantum data is reduced to 1 while the size of classical secret shares also is also reduced to l−2 m−1 based on ((m+1, n′)) threshold and to l−2 r2 (where r2 is the number of maximal unqualified sets) based on adversary structure. Consequently, our proposed schemes can greatly reduce the cost and difficulty of generating and storing EPR pairs and lower the risk of transmitting encoded particles.

Family-based programmes for preventing smoking by children and adolescents (Review)

Background There is evidence that family and friends influence children's decisions to smoke. Objectives To assess the effectiveness of interventions to help families stop children starting smoking. Search methods We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO, CINAHL unpublished material, and key articles' reference lists. We performed free-text internet searches and targeted searches of appropriate websites, and hand-searched key journals not available electronically. We consulted authors and experts in the field. The most recent search was 3 April 2014. There were no date or language limitations. Selection criteria Randomised controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and families to deter tobacco use. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. Data collection and analysis We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data for each RCT and assessed them for risk of bias. We pooled risk ratios using a Mantel-Haenszel fixed effect model. Main results Twenty-seven RCTs were included. The interventions were very heterogeneous in the components of the family intervention, the other risk behaviours targeted alongside tobacco, the age of children at baseline and the length of follow-up. Two interventions were tested by two RCTs, one was tested by three RCTs and the remaining 20 distinct interventions were tested only by one RCT. Twenty-three interventions were tested in the USA, two in Europe, one in Australia and one in India. The control conditions fell into two main groups: no intervention or usual care; or school-based interventions provided to all participants. These two groups of studies were considered separately. Most studies had a judgement of 'unclear' for at least one risk of bias criteria, so the quality of evidence was downgraded to moderate. Although there was heterogeneity between studies there was little evidence of statistical heterogeneity in the results. We were unable to extract data from all studies in a format that allowed inclusion in a meta-analysis. There was moderate quality evidence family-based interventions had a positive impact on preventing smoking when compared to a no intervention control. Nine studies (4810 participants) reporting smoking uptake amongst baseline non-smokers could be pooled, but eight studies with about 5000 participants could not be pooled because of insufficient data. The pooled estimate detected a significant reduction in smoking behaviour in the intervention arms (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.68 to 0.84). Most of these studies used intensive interventions. Estimates for the medium and low intensity subgroups were similar but confidence intervals were wide. Two studies in which some of the 4487 participants already had smoking experience at baseline did not detect evidence of effect (RR 1.04, 95% CI 0.93 to 1.17). Eight RCTs compared a combined family plus school intervention to a school intervention only. Of the three studies with data, two RCTS with outcomes for 2301 baseline never smokers detected evidence of an effect (RR 0.85, 95% CI 0.75 to 0.96) and one study with data for 1096 participants not restricted to never users at baseline also detected a benefit (RR 0.60, 95% CI 0.38 to 0.94). The other five studies with about 18,500 participants did not report data in a format allowing meta-analysis. One RCT also compared a family intervention to a school 'good behaviour' intervention and did not detect a difference between the two types of programme (RR 1.05, 95% CI 0.80 to 1.38, n = 388). No studies identified any adverse effects of intervention. Authors' conclusions There is moderate quality evidence to suggest that family-based interventions can have a positive effect on preventing children and adolescents from starting to smoke. There were more studies of high intensity programmes compared to a control group receiving no intervention, than there were for other compairsons. The evidence is therefore strongest for high intensity programmes used independently of school interventions. Programmes typically addressed family functioning, and were introduced when children were between 11 and 14 years old. Based on this moderate quality evidence a family intervention might reduce uptake or experimentation with smoking by between 16 and 32%. However, these findings should be interpreted cautiously because effect estimates could not include data from all studies. Our interpretation is that the common feature of the effective high intensity interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting.

GABAergic inhibition in the fear conditioning circuit of the lateral amygdala is potentiated by dopamine D1 agonists

Auditory fear conditioning is dependent on auditory signaling from the medial geniculate (MGm) and the auditory cortex (TE3) to principal neurons of the lateral amygdala (LA). Local circuit GABAergic interneurons are known to inhibit LA principal neurons via fast and slow IPSP's. Stimulation of MGm and TE3 produces excitatory post-synaptic potentials in both LA principal and interneurons, followed by inhibitory post-synaptic potentials. Manipulations of D1 receptors in the lateral and basal amygdala modulate the retrieval of learned association between an auditory CS and foot shock. Here we examined the effects of D1 agonists on GABAergic IPSP's evoked by stimulation of MGm and TE3 afferents in vitro. Whole cell patch recordings were made from principal neurons of the LA, at room temperature, in coronal brain slices using standard methods. Stimulating electrodes were placed on the fiber tracts medial to the LA and at the external capsule/layer VI border dorsal to the LA to activate (0.1-0.2mA) MGm and TE3 afferents respectively. Neurons were held at -55.0 mV by positive current injection to measure the amplitude of the fast IPSP. Changes in input resistance and membrane potential were measured in the absence of current injection. Stimulation of MGm or TE3 afferents produced EPSP's in the majority of principal neurons and in some an EPSP/IPSP sequence. Stimulation of MGm afferents produced IPSP's with amplitudes of -2.30 ± 0.53 mV and stimulation of TE3 afferents produced IPSP's with amplitudes of -1.98 ± 1.26 mV. Bath application of 20μM SKF38393 increased IPSP amplitudes to -5.94 ± 1.62 mV (MGm, n=3) and-5.46 ± 0.31 mV (TE3, n=3). Maximal effect occurred <10mins. A small increase in resting membrane potential and decrease in input resistance were observed. These data suggest that DA modulates both the auditory thalamic and auditory cortical inputs to the LA fear conditioning circuit via local GABAergic circuits. Supported by NIMH Grants 00956, 46516, and 58911.

Compressive and shear force generated in the lumbar spine of female rowers

Rowers have and accrue greater lumbar spine bone mineral density (BMD) associated with mechanical loading produced during rowing. The aim of this study was to estimate the mechanical loading generated at the lumbar spine (LS) that is apparently providing an osteogenic benefit. The cohort comprised 14 female rowers (average age: 19.7yrs; height: 170.9 cm, weight: 59.5 kg) and 14 female matched controls (average age: 20.9 m yrs; height: 167.5 cm; weight: 58.1 kg). BMD was assessed using the Hologic QDR 2000+ bone densitometer, indicating higher lumbar spine BMD in the rowers compared to the control subjects (1,069 +/- 0.1 vs. 1,027 +/- 0.1 g/cm2). No significant difference existed for BMD at any other site. All rowers performed a six-minute simulated race on a Concept II rowing ergometer. Mechanical loading generated at the lumbar spine during this task was assessed using a two-dimensional model of the spine, enabling the calculation of the compressive and shear forces at L4/L5. The shear force was the joint reaction force perpendicular to the spine at the L4/L5 joint. Peak compressive and shear force at the lumbar spine of the rowers were 2,694 +/- 609 (N) and 660 +/- 117 (N), respectively. Peak compressive force at the LS relative to body weight was 4.6 times body weight. The literature would suggest that forces of this magnitude, generated at the LS during maximal rowing, may be contributing to the site specific higher LS BMD found in the rowers.

Experimentally reduced hip-abductor muscle strength and frontal-plane biomechanics during walking

Researchers have postulated that reduced hip-abductor muscle strength may have a role in the progression of knee osteoarthritis by increasing the external knee-adduction moment. However, the relationship between hip-abductor strength and frontal-plane biomechanics remains unclear. To experimentally reduce hip-abduction strength and observe the subsequent changes in frontal-plane biomechanics. Descriptive laboratory study. Research laboratory. Eight healthy, recreationally active men (age = 27 ± 6 years, height = 1.75 ± 0.11 m, mass = 76.1 ± 10.0 kg). All participants underwent a superior gluteal nerve block injection to reduce the force output of the hip-abductor muscle group. Maximal isometric hip-abduction strength and gait biomechanical data were collected before and after the injections. Gait biomechanical variables collected during walking consisted of knee- and hip-adduction moments and impulses and the peak angles of contralateral pelvic drop, hip adduction, and ipsilateral trunk lean. Hip-abduction strength was reduced after the injection (P = .001) and remained lower than baseline values at the completion of the postinjection gait data collection (P = .02). No alterations in hip- or knee-adduction moments (hip: P = .11; knee: P = .52) or impulses (hip: P = .16; knee: P = .41) were found after the nerve block. Similarly, no changes in angular kinematics were observed for contralateral pelvic drop (P = .53), ipsilateral trunk lean (P = .78), or hip adduction (P = .48). A short-term reduction in hip-abductor strength was not associated with alterations in the frontal-plane gait biomechanics of young, healthy men. Further research is needed to determine whether a similar relationship is true in older adults with knee osteoarthritis.

Prior and posterior linear pooling for combining expert opinions: Uses and impact on Bayesian Networks

The use of expert knowledge to quantify a Bayesian Network (BN) is necessary when data is not available. This however raises questions regarding how opinions from multiple experts can be used in a BN. Linear pooling is a popular method for combining probability assessments from multiple experts. In particular, Prior Linear Pooling (PrLP), which pools opinions then places them into the BN is a common method. This paper firstly proposes an alternative pooling method, Posterior Linear Pooling (PoLP). This method constructs a BN for each expert, then pools the resulting probabilities at the nodes of interest. Secondly, it investigates the advantages and disadvantages of using these pooling methods to combine the opinions of multiple experts. Finally, the methods are applied to an existing BN, the Wayfinding Bayesian Network Model, to investigate the behaviour of different groups of people and how these different methods may be able to capture such differences. The paper focusses on 6 nodes Human Factors, Environmental Factors, Wayfinding, Communication, Visual Elements of Communication and Navigation Pathway, and three subgroups Gender (female, male),Travel Experience (experienced, inexperienced), and Travel Purpose (business, personal) and finds that different behaviors can indeed be captured by the different methods.

Differential segmentation responses to an alcohol social marketing program

Objective This study seeks establish whether meaningful subgroups exist within a 14-16 year old adolescent population and if these segments respond differently to the Game On: Know Alcohol (GOKA) intervention, a school-based alcohol social marketing program. Methodology This study is part of a larger cluster randomized controlled evaluation of the Game On: Know Alcohol (GOKA) program implemented in 14 schools in 2013/2014. TwoStep cluster analysis was conducted to segment 2114 high school adolescents (14-16 years old) on the basis of 22 demographic, behavioral and psychographic variables. Program effects on knowledge, attitudes, behavioral intentions, social norms, expectancies and refusal self-efficacy of identified segments was subsequently examined. Results Three segments were identified: (1) Abstainers (2) Bingers (3) Moderate Drinkers. Program effects varied significantly across segments. The strongest positive change effects post participation were observed for the Bingers, while mixed effects were evident for Moderate Drinkers and Abstainers. Conclusions These findings provide preliminary empirical evidence supporting application of social marketing segmentation in alcohol education programs. Development of targeted programs that meet the unique needs of each of the three identified segments is indicated to extend the social marketing footprint in alcohol education.

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment

In the Solanaceae, a hierarchy of bHLHs confer distinct target specificity to the anthocyanin regulatory complex

The anthocyanin biosynthetic pathway is regulated by a transcription factor complex consisting of an R2R3 MYB, a bHLH, and a WD40. Although R2R3 MYBs belonging to the anthocyanin-activating class have been identified in many plants, and their role well elucidated, the subgroups of bHLH implicated in anthocyanin regulation seem to be more complex. It is not clear whether these potential bHLH partners are biologically interchangeable with redundant functions, or even if heterodimers are involved. In this study, AcMYB110, an R2R3 MYB isolated from kiwifruit (Actinidia sp.) showing a strong activation of the anthocyanin pathway in tobacco (Nicotiana tabacum) was used to examine the function of interacting endogenous bHLH partners. Constitutive expression of AcMYB110 in tobacco leaves revealed different roles for two bHLHs, NtAN1 and NtJAF13. A hierarchical mechanism is shown to control the regulation of transcription factors and consequently of the anthocyanin biosynthetic pathway. Here, a model is proposed for the regulation of the anthocyanin pathway in Solanaceous plants in which AN1 is directly involved in the activation of the biosynthetic genes, whereas JAF13 is involved in the regulation of AN1 transcription.

Exploring the Potential to Educate “Good Citizens” through the Australian Civics and Citizenship Curriculum.

This chapter examines the ways in which notions of ‘a good citizen’ and ‘civic virtue’ have been conceptualized in the new Civics and Citizenship Curriculum for students in Years 3 – 10 in Australia. It argues that whilst Civics and Citizenship Education (CCE) has, over time and in various ways, been recognized as a significant aspect of Australian education, only recently has attention been given to the relational and multidimensional conceptions of citizenship. Considerations of ‘morality’, ‘a good citizen’ and ‘civic virtue’ offer possibilities to engage with multidimensional notions of citizenship, which acknowledge that citizenship perspectives can be affected by personal, social, spatial and temporary situations (Cogan & Derricott, 2000). In the current statement on national goals for schooling in Australia, which informed the development of CCE, the Melbourne Declaration (MCEETYA, 2008) called for young Australians to be educated to “act with moral and ethical integrity” and be “committed to national values of democracy, equity and justice, and participate in Australia’s civic life” (MCEETYA, 2008, pp. 8–9). The chapter claims that this maximal emphasis (McLaughlin, 1992), based on active, values based and interpretive approaches to democratic citizenship which encourage debate and participation in civil society, was evident in the new Civics and Citizenship Curriculum. However, it contends that the recommendations of the recent Review of the Australian Curriculum: Final report (Australian Government, 2014a & b), will now limit CCE’s potential to deliver the sort of active and informed citizenship heralded by the Melbourne Declaration. This is because the Review advocates for a content-focused minimal (McLaughlin, 1992) emphasis on civic knowledge, with diminished attention to citizenship participation and processes. In doing so, the Review foregrounds conceptions of the ‘good citizen’ in more limited terms of responsibility, obligations and compliance with the status quo.

Endurance exercise and DNA stability: Is there a link to duration and intensity?

It is commonly accepted that regular moderate intensity physical activity reduces the risk of developing many diseases. Counter intuitively, however, evidence also exists for oxidative stress resulting from acute and strenuous exercise. Enhanced formation of reactive oxygen and nitrogen species may lead to oxidatively modified lipids, proteins and nucleic acids and possibly disease. Currently, only a few studies have investigated the influence of exercise on DNA stability and damage with conflicting results, small study groups and the use of different sample matrices or methods and result units. This is the first review to address the effect of exercise of various intensities and durations on DNA stability, focusing on human population studies. Furthermore, this article describes the principles and limitations of commonly used methods for the assessment of oxidatively modified DNA and DNA stability. This review is structured according to the type of exercise conducted (field or laboratory based) and the intensity performed (i.e. competitive ultra/endurance exercise or maximal tests until exhaustion). The findings presented here suggest that competitive ultra-endurance exercise (>4h) does not induce persistent DNA damage. However, when considering the effects of endurance exercise (<4h), no clear conclusions could be drawn. Laboratory studies have shown equivocal results (increased or no oxidative stress) after endurance or exhaustive exercise. To clarify which components of exercise participation (i.e. duration, intensity and training status of subjects) have an impact on DNA stability and damage, additional carefully designed studies combining the measurement of DNA damage, gene expression and DNA repair mechanisms before, during and after exercise of differing intensities and durations are required.

Effects of resistance training on measures of muscular strength in people with Parkinson’s disease: A systematic review and meta-analysis

Objective The aim of this systematic review and meta-analysis was to determine the overall effect of resistance training (RT) on measures of muscular strength in people with Parkinson’s disease (PD). Methods Controlled trials with parallel-group-design were identified from computerized literature searching and citation tracking performed until August 2014. Two reviewers independently screened for eligibility and assessed the quality of the studies using the Cochrane risk-of-bias-tool. For each study, mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes based on between-group comparisons using post-intervention data. Subgroup analysis was conducted based on differences in study design. Results Nine studies met the inclusion criteria; all had a moderate to high risk of bias. Pooled data showed that knee extension, knee flexion and leg press strength were significantly greater in PD patients who undertook RT compared to control groups with or without interventions. Subgroups were: RT vs. control-without-intervention, RT vs. control-with-intervention, RT-with-other-form-of-exercise vs. control-without-intervention, RT-with-other-form-of-exercise vs. control-with-intervention. Pooled subgroup analysis showed that RT combined with aerobic/balance/stretching exercise resulted in significantly greater knee extension, knee flexion and leg press strength compared with no-intervention. Compared to treadmill or balance exercise it resulted in greater knee flexion, but not knee extension or leg press strength. RT alone resulted in greater knee extension and flexion strength compared to stretching, but not in greater leg press strength compared to no-intervention. Discussion Overall, the current evidence suggests that exercise interventions that contain RT may be effective in improving muscular strength in people with PD compared with no exercise. However, depending on muscle group and/or training dose, RT may not be superior to other exercise types. Interventions which combine RT with other exercise may be most effective. Findings should be interpreted with caution due to the relatively high risk of bias of most studies.

Analysis of arm elevation muscle activity through different movement planes and speeds during in-water and dry-land exercise

Objective The objectives of this cross-sectional, analytical inference analysis were to compare shoulder muscle activation at arm elevations of 0° to 90° through different movement planes and speeds during in-water and dry-land exercise and to extrapolate this information to a clinical rehabilitation model. Methods Six muscles of right-handed adult subjects (n = 16; males/females: 50%; age: 26.1 ± 4.5 years) were examined with surface electromyography during arm elevation in water and on dry land. Participants randomly performed 3 elevation movements (flexion, abduction, and scaption) through 0° to 90°. Three movement speeds were used for each movement as determined by a metronome (30°/sec, 45°/sec, and 90°/sec). Dry-land maximal voluntary contraction tests were used to determine movement normalization. Results Muscle activity levels were significantly lower in water compared with dry land at 30°/sec and 45°/sec but significantly higher at 90°/sec. This sequential progressive activation with increased movement speed was proportionally higher on transition from gravity-based on-land activity to water-based isokinetic resistance. The pectoralis major and latissimus dorsi muscles showed higher activity during abduction and scaption. Conclusions These findings on muscle activation suggest protocols in which active flexion is introduced first at low speeds (30°/sec) in water, then at medium speeds (45°/sec) in water or on dry land, and finally at high speeds (90°/sec) on dry land before in water. Abduction requires higher stabilization, necessitating its introduction after flexion, with scaption introduced last. This model of progressive sequential movement ensures that early active motion and then stabilization are appropriately introduced. This should reduce rehabilitation time and improve therapeutic goals without compromising patient safety or introducing inappropriate muscle recruitment or movement speed.