Localization of Mineralocorticoid Receptors at Mammalian Synapses

In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

Prediction of muscular architecture of the rectus femoris and vastus lateralis from EMG during isometric contractions in soccer players

Objectives The purpose of the study was to establish regression equations that could be used to predict muscle thickness and pennation angle at different intensities from electromyography (EMG) based measures of muscle activation during isometric contractions. Design Cross-sectional study. Methods Simultaneous ultrasonography and EMG were used to measure pennation angle, muscle thickness and muscle activity of the rectus femoris and vastus lateralis muscles, respectively, during graded isometric knee extension contractions performed on a Cybex dynamometer. Data form fifteen male soccer players were collected in increments of approximately 25% intensity of the maximum voluntary contraction (MVC) ranging from rest to MVC. Results There was a significant correlation (P < 0.05) between ultrasound predictors and EMG measures for the muscle thickness of rectus femoris with an R2 value of 0.68. There was no significant correlation (P > 0.05) between ultrasound pennation angle for the vastus lateralis predictors for EMG muscle activity with an R2 value of 0.40. Conclusions The regression equations can be used to characterise muscle thickness more accurately and to determine how it changes with contraction intensity, this provides improved estimates of muscle force when using musculoskeletal models.

Effect of interval training intensity on fat oxidation, blood lactate and the rate of perceived exertion in obese men

Purpose The objectives of this study were to examine the effect of 4-week moderate- and high-intensity interval training (MIIT and HIIT) on fat oxidation and the responses of blood lactate (BLa) and rating of perceived exertion (RPE). Methods Ten overweight/obese men (age = 29 ±3.7 years, BMI = 30.7 ±3.4 kg/m2) participated in a cross-over study of 4-week MIIT and HIIT training. The MIIT training sessions consisted of 5-min cycling stages at mechanical workloads 20% above and 20% below 45%VO2peak. The HIIT sessions consisted of intervals of 30-s work at 90%VO2peak and 30-s rest. Pre- and post-training assessments included VO2max using a graded exercise test (GXT) and fat oxidation using a 45-min constant-load test at 45%VO2max. BLa and RPE were also measured during the constant-load exercise test. Results There were no significant changes in body composition with either intervention. There were significant increases in fat oxidation after MIIT and HIIT (p ≤ 0.01), with no effect of intensity. BLa during the constant-load exercise test significantly decreased after MIIT and HIIT (p ≤ 0.01), and the difference between MIIT and HIIT was not significant (p = 0.09). RPE significantly decreased after HIIT greater than MIIT (p ≤ 0.05). Conclusion Interval training can increase fat oxidation with no effect of exercise intensity, but BLa and RPE decreased after HIIT to greater extent than MIIT.

Fully Bayesian experimental design for pharmacokinetic studies

Utility functions in Bayesian experimental design are usually based on the posterior distribution. When the posterior is found by simulation, it must be sampled from for each future data set drawn from the prior predictive distribution. Many thousands of posterior distributions are often required. A popular technique in the Bayesian experimental design literature to rapidly obtain samples from the posterior is importance sampling, using the prior as the importance distribution. However, importance sampling will tend to break down if there is a reasonable number of experimental observations and/or the model parameter is high dimensional. In this paper we explore the use of Laplace approximations in the design setting to overcome this drawback. Furthermore, we consider using the Laplace approximation to form the importance distribution to obtain a more efficient importance distribution than the prior. The methodology is motivated by a pharmacokinetic study which investigates the effect of extracorporeal membrane oxygenation on the pharmacokinetics of antibiotics in sheep. The design problem is to find 10 near optimal plasma sampling times which produce precise estimates of pharmacokinetic model parameters/measures of interest. We consider several different utility functions of interest in these studies, which involve the posterior distribution of parameter functions.

Physical activity patterns among South-Asian adults : a systematic review

Physical activity (PA) has many beneficial physical and mental health effects. Physical inactivity is considered the fourth leading risk factor for global mortality. At present there are no systematic reviews on PA patterns among South Asian adults residing in the region. The present study aims to systematically evaluate studies on PA patterns in South Asian countries. A five-staged comprehensive search of the literature was conducted in Medline, Web of Science and SciVerse Scopus using keywords ‘Exercise’, ‘Walking’, ‘Physical activity’, ‘Inactivity’, ‘Physical Activity Questionnaire’, ‘International Physical Activity Questionnaire’, ‘IPAQ’, ‘Global Physical Activity Questionnaire’ and ‘GPAQ’, combined with individual country names. The search was restricted to English language articles conducted in humans and published before 31st December 2012. To obtain additional data a manual search of the reference lists of articles was performed. Data were also retrieved from the search of relevant web sites and online resources. The total number of hits obtained from the initial search was 1,771. The total number of research articles included in the present review is eleven (India-8, Sri Lanka-2, Pakistan-1). In addition, eleven country reports (Nepal-3, Bangladesh-2, India-2, Sri Lanka-2, Bhutan-1, Maldives-1) of World Health Organization STEPS survey from the South-Asian countries were retrieved online. In the research articles the overall prevalence of inactivity was as follows; India (18.5%-88.4%), Pakistan (60.1%) and Sri Lanka (11.0%-31.8%). STEPS survey reports were available from all countries except Pakistan. Overall in majority of STEPS surveys females were more inactive compared to males. Furthermore, leisure related inactivity was >75% in studies reporting inactivity in this domain and people were more active in transport domain when compared with the other domains. In conclusion, our results show that there is a wide variation in the prevalence of physical inactivity among South-Asian adults within and between countries. Furthermore, physical inactivity in South Asian adults was associated with several socio-demographic characteristics. Majority of South Asian adults were inactive during their leisure time. These Factors need to be considered when planning future interventions and research aimed at improving PA in the region.

The health outcomes and costs of people attending an interdisciplinary chronic disease service in regional Australia : protocol for a longitudinal cohort investigation

Background Rates of chronic disease are escalating around the world. To date health service evaluations have focused on interventions for single chronic diseases. However, evaluations of the effectiveness of new intervention strategies that target single chronic diseases as well as multimorbidity are required, particularly in areas outside major metropolitan centres where access to services, such as specialist care, is difficult and where the retention and recruitment of health professionals affects service provision. Methods This study is a longitudinal investigation with a baseline and three follow-up assessments comparing the health and health costs of people with chronic disease before and after intervention at a chronic disease clinic, in regional Australia. The clinic is led by students under the supervision of health professionals. The study will provide preliminary evidence regarding the effectiveness of the intervention, and evaluate the influence of a range of factors on the health outcomes and costs of the patients attending the clinic. Patients will be evaluated at baseline (intake to the service), and at 3-, 6-, and 12-months after intake to the service. Health will be measured using the SF-36 and health costs will be measured using government and medical record sources. The intervention involves students and health professionals from multiple professions working together to treat patients with programs that include education and exercise therapy programs for back pain, and Healthy Lifestyle programs; as well as individual consultations involving single professions. Discussion Understanding the effect of a range of factors on the health state and health costs of people attending an interdisciplinary clinic will inform health service provision for this clinical group and will determine which factors need to be controlled for in future observational studies. Preliminary evidence regarding changes in health and health costs associated with the intervention will be a platform for future clinical trials of intervention effectiveness. The results will be of interest to teams investigating new chronic disease programs particularly for people with multimorbidity, and in areas outside major metropolitan centres.

Long-term survival after intensive care unit discharge in Thailand : a retrospective study

Introduction Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country. Methods In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy. Results This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population. Conclusions Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.

The impact of the clean development mechanism (CDM) on the cost price of wind power electricity : a China study

As a renewable energy source, wind power is playing an increasingly important role in China’s electricity supply. Meanwhile, China is also the world’s largest market for Clean Development Mechanism (CDM) wind power projects. Based on the data of 27 wind power projects of Inner Mongolia registered with the Executive Board of the United Nations (EB) in 2010, this paper constructs a financial model of Net Present Value (NPV) to analyze the cost of wind power electricity. A sensitivity analysis is then conducted to examine the impact of different variables with and without Certified Emission Reduction (CER) income brought about by the CDM. It is concluded that the CDM, along with static investment and annual wind electricity production, is one of the most significant factors in promoting the development of wind power in China. Additionally, wind power is envisaged as a practical proposition for competing with thermal power if the appropriate actions identified in the paper are made.

BIM : enabling sustainability and asset management through knowledge management

Building Information Modeling (BIM) is the use of virtual building information models to develop building design solutions and design documentation and to analyse construction processes. Recent advances in IT have enabled advanced knowledge management, which in turn facilitates sustainability and improves asset management in the civil construction industry. There are several important qualifiers and some disadvantages of the current suite of technologies. This paper outlines the benefits, enablers, and barriers associated with BIM and makes suggestions about how these issues may be addressed. The paper highlights the advantages of BIM, particularly the increased utility and speed, enhanced fault finding in all construction phases, and enhanced collaborations and visualisation of data. The paper additionally identifies a range of issues concerning the implementation of BIM as follows: IP, liability, risks, and contracts and the authenticity of users. Implementing BIM requires investment in new technology, skills training, and development of new ways of collaboration and Trade Practices concerns. However, when these challenges are overcome, BIM as a new information technology promises a new level of collaborative engineering knowledge management, designed to facilitate sustainability and asset management issues in design, construction, asset management practices, and eventually decommissioning for the civil engineering industry.

Differential entrainment of neuroelectric delta oscillations in developmental dyslexia

Oscillatory entrainment to the speech signal is important for language processing, but has not yet been studied in developmental disorders of language. Developmental dyslexia, a difficulty in acquiring efficient reading skills linked to difficulties with phonology (the sound structure of language), has been associated with behavioural entrainment deficits. It has been proposed that the phonological ‘deficit’ that characterises dyslexia across languages is related to impaired auditory entrainment to speech at lower frequencies via neuroelectric oscillations (<10 Hz, ‘temporal sampling theory’). Impaired entrainment to temporal modulations at lower frequencies would affect the recovery of the prosodic and syllabic structure of speech. Here we investigated event-related oscillatory EEG activity and contingent negative variation (CNV) to auditory rhythmic tone streams delivered at frequencies within the delta band (2 Hz, 1.5 Hz), relevant to sampling stressed syllables in speech. Given prior behavioural entrainment findings at these rates, we predicted functionally atypical entrainment of delta oscillations in dyslexia. Participants performed a rhythmic expectancy task, detecting occasional white noise targets interspersed with tones occurring regularly at rates of 2 Hz or 1.5 Hz. Both groups showed significant entrainment of delta oscillations to the rhythmic stimulus stream, however the strength of inter-trial delta phase coherence (ITC, ‘phase locking’) and the CNV were both significantly weaker in dyslexics, suggestive of weaker entrainment and less preparatory brain activity. Both ITC strength and CNV amplitude were significantly related to individual differences in language processing and reading. Additionally, the instantaneous phase of prestimulus delta oscillation predicted behavioural responding (response time) for control participants only.

What makes school leaders inspirational and how does this relate to mentoring?

Leadership comes in many forms (such as transactional, transformational, distributed) and its effectiveness can inspire others to achieve organisational goals and visions. Inspiration as an emotional event requires receptiveness and an awareness of social interdependence. When mentees are inspired by mentor role models they can extend personal attributes and practices. Similar to other leaders, inspiring mentors can motivate mentees to develop a strength of character and achieve goals in the workplace. What makes school leaders inspirational and how does this relate to mentoring? This qualitative study collects data from 25 experienced teachers, which involved written questionnaire, work samples, and audio-recorded focus group discussions. These participants indicated that inspirational school leaders were those who had: (1) organisational goals (e.g., visionary, goal driven, innovative, & motivational); (2) professional skills such as being knowledgeable, communicative, and acknowledging others’ achievements; and (3) personal attributes (e.g., integrity, active listening, respectful, enthusiastic, & approachable). This research shows how mentors and school leaders can consider the inspirational attributes and practices outlined by participants in this study to inspire teaching staff. For example, an awareness of attentive listening, motivational and visionary practices, and acknowledging individual achievements can guide school leaders and mentors to inspire others for achieving organsational goals and visions.

The cultural impact of institutional remix : the formalisation of textual reappropriation within the ABC

In 2009, Mark Deuze proposed an updated approach to media studies to incorporate ‘media life’, a concept he suggests addresses the invisibleness of ubiquitous media. Media life provides a useful lens for researchers to understand the human condition in media and not with media. At a similar time, public service media (PSM) strategies have aligned audience participation with the so‐called Reithian trinity which suggest the PSB should inform, educate and entertain while performing its core values of public service broadcasting (Enli 2008). Remix within the PSM institution relies on audience participation, employing ‘the people formerly known as the audience’ (Rosen 2006) as cultural artifact producers, and draws on their experience from within the media. Remix as a practice then enables us to examine the shift of the core PSM values by understanding how audience participation, informed by a human condition mobilised from our existence of being in media and not merely with media. However, remix within PSM challenges the once elitist construction of meaning models with an egalitarian approach towards socially reappropriated texts, questioning its affect on the cultural landscape. This paper draws on three years of ethnographic data from within the Australian Broadcasting Corporation (ABC), exploring the remix culture of ABC Pool. ABC Pool operates under a Creative Commons licensing regime to enable remix practice under the auspices of the ABC. ABC Pool users provide a useful group of remix practitioners to examine as they had access to a vast ABC archival collection and were invited to remix those cultural artefacts, often adding cultural and fiscal value. This paper maintains a focus on the audience participation within PSM through remix culture by applying media dependency theory to remix as cultural practice and calls to expand and update the societal representation within the ABC.

Exosomes in prostate cancer: Putting together the pieces of a puzzle

Exosomes have been shown to act as mediators for cell to cell communication and as a potential source of biomarkers for many diseases, including prostate cancer. Exosomes are nanosized vesicles secreted by cells and consist of proteins normally found in multivesicular bodies, RNA, DNA and lipids. As a potential source of biomarkers, exosomes have attracted considerable attention, as their protein content resembles that of their cells of origin, even though it is noted that the proteins, miRNAs and lipids found in the exosomes are not a reflective stoichiometric sampling of the contents from the parent cells. While the biogenesis of exosomes in dendritic cells and platelets has been extensively characterized, much less is known about the biogenesis of exosomes in cancer cells. An understanding of the processes involved in prostate cancer will help to further elucidate the role of exosomes and other extracellular vesicles in prostate cancer progression and metastasis. There are few methodologies available for general isolation of exosomes, however validation of those methodologies is necessary to study the role of exosomal-derived biomarkers in various diseases. In this review, we discuss “exosomes” as a member of the family of extracellular vesicles and their potential to provide candidate biomarkers for prostate cancer.

Othering the Malay in Malaysia : a planned consequence of politics?

This paper examines the rise in the politicisation of Islam in Malaysia and links it to the othering of the Malaysian Malay. It is my argument that both were “conquering” tools of Malaysia’s “Father of Modernisation”, Mahathir Mohamad, devised to win the support of the Malay Muslim majority in Malaysia. The many awards bestowed on Mahathir obscure the fact that he was instrumental in the systematic erosion of the power and roles of state institutions, especially at the Federal government level. This includes the significant loss of the independence of the Malaysian judiciary. Whilst per capita income in Malaysia may well have increased eight times under his 22-year leadership, this paper asks why is it that the majority of the Malays remain the largest number among the poor and the more disenfranchised of ethnicities in the country? Why have Malay and Muslim women suffered such a rapid decreasing ability to access justice? This paper examines existing research on the social and political changes Malaysia has experienced with Islamisation and under Mahathir’s rule, as well as studies on Malayness, Malay nationalism and Muslim Malay identity formation. The paper elaborates the othering of a majority people, the Malays in Malaysia, and how this othering has brought forth a fast-growing political power in the name of a supremacist Islam, a puritanical Sunni and Malay Islam. Specific events in the rise and rule of Mahathir as Malaysia’s then Prime Minister are reviewed, such as the banning of The Malay Dilemma, and the split in the United Malays National Organisation (UMNO) in 1987. Also examined is the varying emphasis between Muslim and race, and how during Mahathir’s rule, that strong misogynist and patriarchal attitudes took hold in Malay Muslim consciousness, a colonising consciousness that is othering the perceived cultural and genetic “impurities” within the Malay.

The state of the art defence : defining the Australian experience in the context of pharmaceuticals

One of the defences within Part 3-5 of the Australian Consumer Law is the state of the art, or development risk defence. This defence, although significant, has often been neglected in Australian jurisprudential analysis and has triggered at most generic academic analysis. However, with the rise of pharmaceutical and medical device litigation in Australia, it could become a vital weapon for Australian manufacturers against product liability claims. This paper will firstly review the two ways this defence could operate. It will also discuss the three types of defects which the defence could apply to. This paper aims to determine exactly when and how this defence should apply in Australia, in the context of pharmaceutical product liability claims.