Modulating exercise-induced hormesis: Does less equal more?

Hormesis enco 16 mpasses the notion that low levels of stress stimulate or upregulate 17 existing cellular and molecular pathways that improve the capacity of cells and organisms to 18 withstand greater stress. This notion underlies much of what we know about how exercise 19 conditions the body and induces long-term adaptations. During exercise, the body is 20 exposed to various forms of stress, including thermal, metabolic, hypoxic, oxidative, and 21 mechanical stress. These stressors activate biochemical messengers, which in turn activate 22 various signaling pathways that regulate gene expression and adaptive responses. 23 Historically, antioxidant supplements, nonsteroidal anti-inflammatory drugs, and 24 cryotherapy have been favored to attenuate or counteract exercise-induced oxidative stress 25 and inflammation. However, reactive oxygen species and inflammatory mediators are key 26 signaling molecules in muscle, and such strategies may mitigate adaptations to exercise. 27 Conversely, withholding dietary carbohydrate and restricting muscle blood flow during 28 exercise may augment adaptations to exercise. In this review article, we combine, integrate, 29 and apply knowledge about the fundamental mechanisms of exercise adaptation. We also 30 critically evaluate the rationale for using interventions that target these mechanisms under 31 the overarching concept of hormesis. There is currently insufficient evidence to establish 32 whether these treatments exert dose-dependent effects on muscle adaptation. However, 33 there appears to be some dissociation between the biochemical/molecular effects and 34 functional/performance outcomes of some of these treatments. Although several of these 35 treatments influence common kinases, transcription factors and proteins, it remains to be 36 determined if these interventions complement or negate each other, and whether such 37 effects are strong enough to influence adaptations to exercise.

3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

More than just audiences : Developing communitas and social inclusion through theatre participation for young people

In a Facebook conversation about theatre going by young people in Brisbane playwright Valerie Foley noted, “theatre in and of itself may not have the cultural value it once had”. This chapter explores how three Australian live theatre/performance events – World Theatre Festival (Brisbane 2011 and 2012), Backbone’s annual 2High Festival (Brisbane 2012) and Next Wave Festival (Melbourne 2012) - repositioned the value of live performing arts to develop social cohesion and wellbeing for young people. The chapter draws out how these performance events developed communitas (Turner 2012) for young audiences.

Sun, sun and more sun — how to register as a pharmacist in Australia

To me, Australia has always seemed like an alluring destination, with its beautiful beaches, amazing wildlife and beautiful coastal cities. For some years, there have been many pharmacists who have enjoyed working and travelling around this country. Recently, though, there have been a number of changes made to the registration process, which has made this aspiration more difficult...

Growing more sustainable communities

According to the Green Building Council of Australia, some 85 per cent of the Australian population is now concentrated in cities, and the nation’s population is expected to rise by 60 per cent by 2050. Clearly, the coming decade will see a greater emphasis not only on environmental impacts, but also the social impacts of our expanding urban areas.

Impact of adolescent peer aggression on later educational and employment outcomes in an Australian cohort

This study used prospective birth cohort data to analyse the relationship between peer aggression at 14 years of age and educational and employment outcomes at 17 years (N = 1091) and 20 years (N = 1003). Participants from the Western Australian Pregnancy Cohort (Raine) study were divided into mutually exclusive categories of peer aggression. Involvement in peer aggression was reported by 40.2% (10.1% victims; 21.4% perpetrators; 8.7% victim–perpetrators) of participants. Participants involved in any form of peer aggression were less likely to complete secondary school. Perpetrators and victim–perpetrators of peer aggression were more likely to be in the ‘No Education, Employment or Training’ group at 20 years of age. This association was explained by non-completion of secondary school. These findings demonstrate a robust association between involvement in peer aggression and non-completion of secondary school, which in turn was associated with an increased risk of poor educational and employment outcomes in early adulthood.

Systemic ideation: A playbook for creating innovative ideas more consciously

When looking for innovative ideas, we all wish we were Larry Page or Mark Zuckerberg with the “next big thingˮ. However, not all companies have geniuses like them, nor do they need them. What is needed is a systemic approach for consciously developing ideas.

Associations between individual socioeconomic position, neighbourhood disadvantage, and transport mode: Baseline results from the HABITAT multilevel study

Background Understanding how different socioeconomic indicators are associated with transport modes provide insight into which interventions might contribute to reducing socioeconomic inequalities in health. The purpose of this study was to examine associations between neighbourhood-level socioeconomic disadvantage, individual-level socioeconomic position (SEP) and usual transport mode. Methods This investigation included 11,036 residents from 200 neighbourhoods in Brisbane, Australia. Respondents self-reported their usual transport mode (car or motorbike, public transport, walking or cycling). Indicators for individual-level SEP were education, occupation, and household income; and neighbourhood disadvantage was measured using a census-derived index. Data were analysed using multilevel multinomial logistic regression. High SEP respondents and residents of the most advantaged neighbourhoods who used a private motor vehicle as their usual form of transport was the reference category. Results Compared with driving a motor vehicle, the odds of using public transport were higher for white collar employees (OR1.68, 95%CrI 1.41-2.01), members of lower income households (OR 1.71 95%CrI 1.25-2.30), and residents of more disadvantaged neighbourhoods (OR 1.93, 95%CrI 1.46-2.54); and lower for respondents with a certificate-level education (OR 0.60, 95%CrI 0.49-0.74) and blue collar workers (OR 0.63, 95%CrI 0.50-0.81). The odds of walking for transport were higher for the least educated (OR 1.58, 95%CrI 1.18-2.11), those not in the labour force (OR 1.94, 95%CrI 1.38-2.72), members of lower income households (OR 2.10, 95%CrI 1.23-3.64), and residents of more disadvantaged neighbourhoods (OR 2.73, 95%CrI 1.46-5.24). The odds of cycling were lower among less educated groups (OR 0.31, 95% CrI 0.19-0.48). Conclusion The relationships between socioeconomic characteristics and transport modes are complex, and provide challenges for those attempting to encourage active forms of transportation. Further work is required exploring the individual- and neighbourhood-level mechanisms behind transport mode choice, and what factors might influence individuals from different socioeconomic backgrounds to change to more active transport modes.

Party On! A call for entrepreneurship research that is more interactive, activity based, cognitively hot, compassionate, and prosocial

It is the Journal of Business Venturing's (JBV) 30th birthday. Although the community of entrepreneurship scholars deserves to celebrate JBV's achievements over the last 30 years (and congratulate the journal's parents—Ian Macmillan and S. Venkataraman), my focus is more on the future of entrepreneurship (and by extension JBV). A focus on entrepreneurship is both timeless and timely. On the one hand, entrepreneurship is timeless given the long-recognized importance of entrepreneurs to economies and societies (e.g., Jean Baptiste who supposedly coined the term in about 1800). On the other hand, a discussion of entrepreneurship is timely because now that the field of entrepreneurship has achieved legitimacy, it faces both opportunities and threats. It is thus timely to acknowledge the threats and think about opportunities to advance the field. A discussion of entrepreneurship is also timely because society faces a number of grand challenges (including the durability of poverty, environmental degradation [ Dorado and Ventresca, 2013]), challenges well suited to entrepreneurial responses...

Hole mobility of 3.56 cm2V−1s−1accomplished using more extended dithienothiophene with furan flanked diketopyrrolopyrrole polymer

A highly extended dithienothiophene comonomer building block was used in combination with highly fused aromatic furan substituted diketopyrrolopyrrole for the synthesis of novel donor–acceptor alternating copolymer PDPPF-DTT. Upon testing PDPPF-DTT as a channel semiconductor in top contact bottom gate organic field effect transistors (OFETs), it was found to exhibit p-channel behaviour. The highest hole mobility of 3.56 cm2 V−1 s−1 was reported for PDPPF-DTT. To our knowledge, this is the highest mobility reported so far for the furan flanked diketopyrrolopyrrole class of copolymers using conventional device geometry with straightforward processing.

Life-course determinants of bone mass in young adults from a transitional rural community in India: The Andhra Pradesh Children and Parents Study (APCAPS)

Background: Undernutrition and physical inactivity are both associated with lower bone mass. Objective: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. Design: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987–1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009–2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18–23 y). Results: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm2; lumbar spine: 0.86 (women), 0.93 (men) g/cm2]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. Conclusions: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.

More than thirty years of ultimatum bargaining experiments: Motives, variations, and a survey of the recent literature

Take-it or leave-it offers are probably as old as mankind. Our objective here is, first, to provide a, probably subjectively colored, recollection of the initial ultimatum game experiment, its motivation and the immediate responses. Second, we discuss extensions of the standard ultimatum bargaining game in a unified framework, and, third, we offer a survey of the experimental ultimatum bargaining literature containing papers published since the turn of the century. The paper argues that the ultimatum game is a versatile tool for research in bargaining and on social preferences. Finally, we provide examples for open research questions and directions for future studies.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Computer-assisted sampling of acoustic data for more efficient determination of bird species richness

Bird species richness survey is one of the most intriguing ecological topics for evaluating environmental health. Here, bird species richness denotes the number of unique bird species in a particular area. Factors affecting the investigation of bird species richness include weather, observation bias, and most importantly, the prohibitive costs of conducting surveys at large spatiotemporal scales. Thanks to advances in recording techniques, these problems have been alleviated by deploying sensors for acoustic data collection. Although automated detection techniques have been introduced to identify various bird species, the innate complexity of bird vocalizations, the background noise present in the recording and the escalating volumes of acoustic data pose a challenging task on determination of bird species richness. In this paper we proposed a two-step computer-assisted sampling approach for determining bird species richness in one-day acoustic data. First, a classification model is built based on acoustic indices for filtering out minutes that contain few bird species. Then the classified bird minutes are ordered by an acoustic index and the redundant temporal minutes are removed from the ranked minute sequence. The experimental results show that our method is more efficient in directing experts for determination of bird species compared with the previous methods.