(-)-CGP12177 increases contractile force through beta1l-adrenoceptors but not through beta3-adrenoceptors in human right atrial myocardium

(-)-CGP12177 is a non-conventional partial agonist that causes modest and transient increases of contractile force in human atrial trabeculae (Kaumann and Molenaar, 2008). These effects are markedly increased and maintained by inhibition of phosphodiesterase PDE3. As verified with recombinant receptors, the cardiostimulant effect of (-)-CGP12177 is mediated through a site at the beta1-adrenoceptor with lower affinity (beta1LAR) compared to the site through which (-)-CGP12177 antagonizes the effects of catecholamines (beta1HAR). However, in a recent report it was proposed that the positive inotropic effects of CGP12177 are mediated through beta3-adrenoceptors (Skeberdis et al 2008). We therefore investigated whether the effects of (-)-CGP12177 on human atrial trabeculae are antagonized by the beta3-adrenoceptor-selective antagonist L-748,337 (1 microM). (-)-CGP12177 (200 nM) caused a stable increase in force which was significantly reduced by the addition of (-)-bupranolol (1 microM), P = 0.002, (basal 4.45 ± 0.78 mN, IBMX (PDE inhibitor) 5.47 ± 1.01 mN, (-)-CGP12177 9.34 ± 1.33 mN, (-)-bupranolol 5.79 ± 1.08 mN, n = 6) but not affected by the addition of L-748,337 (1 microM), P = 0.12, (basal 4.48 ± 1.32 mN, IBMX 7.15 ± 2.28 mN, (-)-CGP12177 12.51 ± 3.71 mN, L-748,337 10.90 ± 3.49 mN, n = 6). Cumulative concentration-effect curves for (-)-CGP12177 were not shifted to the right by L-748,337 (1 microM). The –logEC50M values of (-)-CGP12177 in the absence and presence of L-748,337 were 7.21±0.09 and 7.41±0.13, respectively (data from 25 trabeculae from 8 patients, P=0.2) The positive inotropic effects of (-)-CGP12177 (IBMX present) were not antagonized by L-748,337 but were blunted by (-)-bupranolol (1 microM). The results rule out an involvement of beta3-adrenoceptors in the positive inotropic effects (-)-CGP12177 in human right atrial myocardium and are consistent with mediation through beta1LAR. Kaumann A and Molenaar P (2008) Pharmacol Ther 118, 303-336 Skeberdis VA et al (2008) J Clin Invest, 118, 3219-3227

Rigour versus Relevance Revisited : Evidence from IS Conference Reviewing Practice

A commonly held belief in the IS discipline is that rigour and relevance are contrary to each other and that addressing both is virtually impossible. It is also believed widely that the editorial practices of our premier conferences and journals over-emphasise rigour on the cost of relevance. However, while these two topics have been filled with numerous subjective discussions, more solid evidence into the true relationship between rigour and relevance and the impact of conference editors on this relationship is still outstanding. This paper contributes to this debate by deriving empirical evidence from a comprehensive and detailed analysis of the characteristics of the submissions and the reviewing practices of three recent IS conferences. It provides first insights into the actual relationship between rigour and relevance and into the role conference chairs play in balancing rigour and relevance. Besides the outcomes that the current set of evaluation criteria does not provide a straight forward proxy for relevance to practitioners, the paper offers two main contributions. First, empirical insights are provided that rigour and relevance do in fact not have to be mutually exclusive. Second, the editorial practices at conferences are skewed towards rigorous papers rather than relevant papers.

Exercise alone is not enough : weight loss also needs a healthy (Mediterranean) diet?

Objective: In the majority of exercise intervention studies, the aggregate reported weight loss is often small. The efficacy of exercise as a weight loss tool remains in question. The aim of the present study was to investigate the variability in appetite and body weight when participants engaged in a supervised and monitored exercise programme. ---------- Design: Fifty-eight obese men and women (BMI = 31·8 ± 4·5 kg/m2) were prescribed exercise to expend approximately 2092 kJ (500 kcal) per session, five times a week at an intensity of 70 % maximum heart rate for 12 weeks under supervised conditions in the research unit. Body weight and composition, total daily energy intake and various health markers were measured at weeks 0, 4, 8 and 12. ---------- Results: Mean reduction in body weight (3·2 ± 1·98 kg) was significant (P < 0·001); however, there was large individual variability (−14·7 to +2·7 kg). This large variability could be largely attributed to the differences in energy intake over the 12-week intervention. Those participants who failed to lose meaningful weight increased their food intake and reduced intake of fruits and vegetables. ---------- Conclusion: These data have demonstrated that even when exercise energy expenditure is high, a healthy diet is still required for weight loss to occur in many people.

Metabolic syndrome and serum carotenoids : findings of a cross-sectional study in Queensland, Australia

Several components of the metabolic syndrome, particularly diabetes and cardiovascular disease, are known to be oxidative stress-related conditions and there is research to suggest that antioxidant nutrients may play a protective role in these conditions. Carotenoids are compounds derived primarily from plants and several have been shown to be potent antioxidant nutrients. The aim of this study was to examine the associations between metabolic syndrome status and major serum carotenoids in adult Australians. Data on the presence of the metabolic syndrome, based on International Diabetes Federation 2005 criteria, were collected from 1523 adults aged 25 years and over in six randomly selected urban centers in Queensland, Australia, using a cross-sectional study design. Weight, height, BMI, waist circumference, blood pressure, fasting and 2-hour blood glucose and lipids were determined, as well as five serum carotenoids. Mean serum alpha-carotene, beta-carotene and the sum of the five carotenoid concentrations were significantly lower (p<0.05) in persons with the metabolic syndrome (after adjusting for age, sex, education, BMI status, alcohol intake, smoking, physical activity status and vitamin/mineral use) than persons without the syndrome. Alpha, beta and total carotenoids also decreased significantly (p<0.05) with increased number of components of the metabolic syndrome, after adjusting for these confounders. These differences were significant among former smokers and non-smokers, but not in current smokers. Low concentrations of serum alpha-carotene, beta-carotene and the sum of five carotenoids appear to be associated with metabolic syndrome status. Additional research, particularly longitudinal studies, may help to determine if these associations are causally related to the metabolic syndrome, or are a result of the pathologies of the syndrome.

How current pedagogy methods in games teaching in the UK, Australia and the US have been shaped by historical, socio cultural, environmental and political constraints

Crucial to enhancing the status and quality of games teaching in schools is a developed understanding of the teaching strategies adopted by practitioners. In this paper, we will demonstrate that contemporary games‟ teaching is a product of individual, task and environmental constraints (Newell, 1986). More specifically, we will show that current pedagogy in the U.K., Australia and the United States is strongly influenced by historical, socio-cultural environmental and political constraints. In summary, we will aim to answer the question „why do teachers teach games the way they do.‟ In answering this question, we conclude that teacher educators, who are trying to influence pedagogical practice, must understand these potential constraints and provide appropriate pre-service experiences to give future physical education teachers the knowledge, confidence and ability to adopt a range of teaching styles when they become fully fledged teachers. Essential to this process is the need to enable future practitioners to base their pedagogical practice on a sound understanding of contemporary learning theories of skill acquisition.

Introduction : the global flow of creative ideas

In the era of late modernism, various pressures play a decisive role in shaping the texture and meaning of the world around us. Population, work, transportation, new technologies of information and communication, lifestyle cultures and other forces are increasingly mobile, and this in turn helps make for a new set of public and personal surroundings. Social life everywhere now appears to share more and more in an international (if not a global) order, even if inequality and stratification remain common inside territories and across territories. Still, the perception is that a particular cultural life is increasingly universal. More and more consumers come to share in its practices and products, with those products becoming more and more homogeneous. This standardization argument finds much support in the apparent internationalization of many elements of media, entertainment, leisure and lifestyle cultures, with cultural conglomerates determined to maximize their global market reach. Once upon a time, in order to understand the economic, political and cultural forces affecting citizens and society, it was mostly deemed sufficient to look within the boundaries of the nation-state. Over the past two decades, these same pressures of globalization have impacted on critical research, highlighting the methodological need to adopt an optic that is more cross-border and transcultural as a means of gaining greater understanding of cultural life.

Same-sex intimate partner violence : exploring the parameters

Intimate partner violence (IPV) is not only a problem for heterosexual couples. Although research in the area is beset by methodological and definitional problems, studies generally demonstrate that IPV also affects those who identify as non-heterosexual; that is, those sexualities that are typically categorized as lesbian, gay, bisexual, transgender, or intersex (LGBTI). IPV appears to be at least as prevalent in LGBTI relationships as it is in heterosexual couples, and follows similar patterns (e.g. Australian Research Centre on Sex, Health and Society 2006; Donovan et al. 2006; Chan 2005; Craft and Serovich 2005; Burke et al. 2002; Jeffries and Ball 2008; Kelly and Warshafsky 1987; Letellier 1994; Turrell 2000; Ristock 2003; Vickers 1996). There is, however, little in the way of specific community or social services support available to either victims or perpetrators of violence in same-sex relationships (see Vickers 1996). In addition, there are important differences in the experience of IPV between LGBTI and non-LGBTI victims, and even among LGBTI individuals; for example, among transgender populations (Chan 2005), and those who are HIV sero-positive (Craft and Serovich 2005). These different experiences of IPV include the use of HIV and the threat of “outing” a partner as tools of control, as just two examples (Jeffries and Ball 2008; Salyer 1999; WA Government 2008b). Such differences impact on how LGBTI victims respond to the violence, including whether or not and how they seek help, what services they are able to avail themselves of, and how likely they are to remain with, or return to, their violent partners (Burke et al. 2002). This chapter explores the prevalent heteronormative discourses that surround IPV, both within the academic literature, and in general social and government discourses. It seeks to understand how same-sex IPV remains largely invisible, and suggests that these dominant discourses play a major role in maintaining this invisibility. In many respects, it builds on work by a number of scholars who have begun to interrogate the criminal justice and social discourses surrounding violent crime, primarily sexual violence, and who problematize these discourses (see for example Carmody 2003; Carmody and Carrington 2000; Marcus 1992). It will begin by outlining these dominant discourses, and then problematize these by identifying some of the important differences between LGBTI IPV and IPV in heterosexual relationships. In doing so, this chapter will suggest some possible reasons for the silence regarding IPV in LGBTI relationships, and the effects that this can have on victims. Although an equally important area of research, and another point at which the limitations of dominant social discourses surrounding IPV can be brought to light, this chapter will not examine violence experienced by heterosexual men at the hands of their intimate female partners. Instead, it will restrict itself to IPV perpetrated within same-sex relationships.

Asia

Reporters sans frontiéres (RSF) has repeatedly declared Asia to be the most demanding continent for journalists and their news organizations to operate in, and in some countries, even simply to survive in. The many reports issued by RSF and other global agencies regularly show Asia to be the region in which the largest number of murders of journalists occur per year, even when Asian–Arabic states and Central Asia are not included in the definition of ‘Asia’. The reports describe numerous physical, legal and economic threats as well as serious political repression and restrictions that journalists face as they attempt to function as watch-dogs, agenda-setters and gate-keepers for their societies. The statistics and examples provided within these reports, however, do not provide the full picture. Most Asian nations also host vibrant media cultures in which journalists play an important role in supporting social and democratic processes and activities. This chapter outlines the political and economic influences on Asian journalism; the impact of new technologies; the debates about philosophies such as 'development journalism', 'peace journalism' and 'Asian values'; and the influence of the so-called 'envelope culture' or practices of gift-giving and bribery that pervade journalism in some countries. To illustrate how these principles affect journalists' practice, the chapter presents a comparison of the starkly contrasting situations in India versus North Korea (Democratic People's Republic of Korea). The chapter also describes issues affecting countries as far afield as China to Kazakhstan, including a short case study of journalism during the so-called Saffron Revolution in Burma in 2007. The chapter concludes with suggestions about how training and aid for the Asian should be contextualized to take into account the specific cultural, economic and political factors that shape and limit the media’s performance, and how journalists might be best placed to negotiate around them. Such training needs to be sensitive to valid variations in perceptions of what kind of governance and journalism best serves development, without serving politically motivated rhetoric.

It's time to be more serious about activating youngsters : lessons for childhood obesity

The epidemic of obesity is impacting an increasing proportion of children, adolescents and adults with a common feature being low levels of physical activity (PA). Despite having more knowledge than ever before about the benefits of PA for health and the growth and development of youngsters, we are only paying lip-service to the development of motor skills in children. Fun, enjoyment and basic skills are the essential underpinnings of meaningful participation in PA. A concurrent problem is the reported increase in sitting time with the most common sedentary behaviors being TV viewing and other screen-based games. Limitations of time have contributed to a displacement of active behaviors with inactive pursuits, which has contributed to reductions in activity energy expenditure. To redress the energy imbalance in overweight and obese children, we urgently need out-of-the-box multisectoral solutions. There is little to be gained from a shame and blame mentality where individuals, their parents, teachers and other groups are singled out as causes of the problem. Such an approach does little more than shift attention from the main game of prevention and management of the condition, which requires a concerted, whole-of-government approach (in each country). The failure to support and encourage all young people to participate in regular PA will increase the chance that our children will live shorter and less healthy lives than their parents. In short, we need novel environmental approaches to foster a systematic increase in PA. This paper provides examples of opportunities and challenges for PA strategies to prevent obesity with a particular emphasis on the school and home settings.

The innovation deficit in public services : the curious problem of too much efficiency and not enough waste and failure

It has long been recognised that government and public sector services suffer an innovation deficit compared to private or market-based services. This paper argues that this can be explained as an unintended consequence of the concerted public sector drive toward the elimination of waste through efficiency, accountability and transparency. Yet in an evolving economy this can be a false efficiency, as it also eliminates the 'good waste' that is a necessary cost of experimentation. This results in a systematic trade0off in the public sector between the static efficiency of minimizing the misuse of public resources and the dynamic efficiency of experimentation. this is inherently biased against risk and uncertainty and therein, explains why governments find service innovation so difficult. In the drive to eliminate static inefficiencies, many political systems have susequently overshot and stifled policy innovation. I propose the 'Red Queen' solution of adaptive economic policy.

Seeing pedestrians at night : visual clutter does not mask biological motion

Although placing reflective markers on pedestrians’ major joints can make pedestrians more conspicuous to drivers at night, it has been suggested that this “biological motion” effect may be reduced when visual clutter is present. We tested whether extraneous points of light affected the ability of 12 younger and 12 older drivers to see pedestrians as they drove on a closed road at night. Pedestrians wore black clothing alone or with retroreflective markings in four different configurations. One pedestrian walked in place and was surrounded by clutter on half of the trials. Another was always surrounded by visual clutter but either walked in place or stood still. Clothing configuration, pedestrian motion, and driver age influenced conspicuity but clutter did not. The results confirm that even in the presence of visual clutter pedestrians wearing biological motion configurations are recognized more often and at greater distances than when they wear a reflective vest.

To have and have not (you don't know what you've got till it's gone)

John Hartley uses the TV show "Dead Like Me" to show how far TV has evolved from the broadcast era.

Contemporary examples where doctors are not immune from non-fatal offences against a person

While it is uncontested that the medical profession makes a valuable contribution to society, doctors should not always be beyond the reach of the criminal law and they should not automatically be treated as God. Doctors should act reasonably and be conscious of their position of trust. In this sense, the notion of “doctors” is construed broadly to include a range of health care professionals such as podiatrists, radiographers, surgeons and general practitioners. This paper will explore contemporary Australian examples where doctors have acted inappropriately and been convicted of non-fatal offences against the person. The physical invasiveness involved in these scenarios varies significantly. In one example, a doctor penetrates a patient’s private body part with a probe for their own sexual gratification, and in another, a doctor covertly visually records a naked patient. The examples will be connected to the theories underpinning criminalisation, particularly social welfare and individual autonomy, with a view to framing guidelines on when doctors should not be immune from non-fatal offences against a person, and thus where the criminal law should respond.

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Inequalities in cardiovascular disease mortality : the role of behavioural, physiological and social risk factors

Background: While the relationship between socioeconomic disadvantage and cardiovascular disease (CVD) is well established, the role that traditional cardiovascular risk factors play in this association remains unclear. We examined the association between education attainment and CVD mortality and the extent to which behavioural, social and physiological factors explained this relationship. Methods: Adults (n=38 355) aged 40-69 years living in Melbourne, Australia were recruited in 1990-1994. Subjects with baseline CVD risk factor data ascertained through questionnaire and physical measurement were followed for an average of 9.4 years with CVD deaths verified by review of medical records and autopsy reports. Results: CVD mortality was higher for those with primary education only compared to those who had completed tertiary education, with a hazard ratio (HR) of 1.66 (95% confidence interval [CI] 1.11-2.49) after adjustment for age, country of birth and gender. Those from the lowest educated group had a more adverse cardiovascular risk factor profile compared to the highest educated group, and adjustment for these risk factors reduced the HR to 1.18 (95% CI 0.78-1.77). In analysis of individual risk factors, smoking and waist circumference explained most of the difference in CVD mortality between the highest and lowest education groups. Conclusions: Most of the excess CVD mortality in lower socioeconomic groups can be explained by known risk factors, particularly smoking and overweight. While targeting cardiovascular risk factors should not divert efforts from addressing the underlying determinants of health inequalities, it is essential that known risk factors are addressed effectively among lower socioeconomic groups.