Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker.

BACKGROUND: Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. METHODS AND RESULTS: Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. CONCLUSIONS: Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

Mathematical models for describing the shape of the in vitro unstretched human crystalline lens

We developed orthogonal least-squares techniques for fitting crystalline lens shapes, and used the bootstrap method to determine uncertainties associated with the estimated vertex radii of curvature and asphericities of five different models. Three existing models were investigated including one that uses two separate conics for the anterior and posterior surfaces, and two whole lens models based on a modulated hyperbolic cosine function and on a generalized conic function. Two new models were proposed including one that uses two interdependent conics and a polynomial based whole lens model. The models were used to describe the in vitro shape for a data set of twenty human lenses with ages 7–82 years. The two-conic-surface model (7 mm zone diameter) and the interdependent surfaces model had significantly lower merit functions than the other three models for the data set, indicating that most likely they can describe human lens shape over a wide age range better than the other models (although with the two-conic-surfaces model being unable to describe the lens equatorial region). Considerable differences were found between some models regarding estimates of radii of curvature and surface asphericities. The hyperbolic cosine model and the new polynomial based whole lens model had the best precision in determining the radii of curvature and surface asphericities across the five considered models. Most models found significant increase in anterior, but not posterior, radius of curvature with age. Most models found a wide scatter of asphericities, but with the asphericities usually being positive and not significantly related to age. As the interdependent surfaces model had lower merit function than three whole lens models, there is further scope to develop an accurate model of the complete shape of human lenses of all ages. The results highlight the continued difficulty in selecting an appropriate model for the crystalline lens shape.

The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model

Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features.

The experience of emotional expression in the context of social relations for people diagnosed with schizophrenia : a phenomenological explication

The experience of emotional expression in the context of social relations is not well understood for people diagnosed with schizophrenia. Early phenomenological research on the experience of people diagnosed with schizophrenia traditionally focussed on self experience in isolation from others, with later research explicating isolated aspects of self experience in relation to others. The current research aimed to focus on the progressive experience of emotional expression of people diagnosed with schizophrenia in relation to others over 12 months, in order to gain a broad spectrum of experience. This study involved unstructured interviews with 7 participants, an average of 4 times each, over a period of 12 months. Due to the unstructured nature of the interviews, a great breadth of experience was explicated. From the interviews there emerged 6 themes grouped together as a transition into, and 5 themes grouped together as a recovery from, symptoms associated with a diagnosis of schizophrenia. Special significance was given to the theme of relational confusion as an experience that provides an understanding of the relationship between social stressors and personal characteristics with responses that are associated with a diagnosis of schizophrenia. It was suggested that participants experienced themselves, including their distancing and isolating responses, as a part of a social system. The breadth of experiences that emerged afforded a framework of experiences within which prior phenomenological research findings on static moments of experience have been located. A more meaningful understanding of the transitioning into and recovery from the experiences associated with a diagnosis of schizophrenia will afford advances in mental health practice.

The role of social capital in reducing negative health outcomes among police officers

This paper investigates the role of social capital on the reduction of short and long run negative health effects associated with stress, as well as indicators of burnout among police officers. Despite the large volume of research on either social capital or the health effects of stress, the interaction of these factors remains an underexplored topic. In this empirical analysis we aim to reduce such a shortcoming focusing on a highly stressful and emotionally draining work environment, namely law enforcement agents who perform as an essential part of maintaining modern society. Using a multivariate regression analysis focusing on three different proxies of health and three proxies for social capital conducting also several robustness checks, we find strong evidence that increased levels of social capital is highly correlated with better health outcomes. Additionally we observe that while social capital at work is very important, social capital in the home environment and work-life balance are even more important. From a policy perspective, our findings suggest that work and stress programs should actively encourage employees to build stronger social networks as well as incorporate better working/home life arrangements.

The properties of the international classification of the external cause of injury when used as an instrument for injury prevention research

Objective: To demonstrate properties of the International Classification of the External Cause of Injury (ICECI) as a tool for use in injury prevention research. Methods: The Childhood Injury Prevention Study (CHIPS) is a prospective longitudinal follow up study of a cohort of 871 children 5–12 years of age, with a nested case crossover component. The ICECI is the latest tool in the International Classification of Diseases (ICD) family and has been designed to improve the precision of coding injury events. The details of all injury events recorded in the study, as well as all measured injury related exposures, were coded using the ICECI. This paper reports a substudy on the utility and practicability of using the ICECI in the CHIPS to record exposures. Interrater reliability was quantified for a sample of injured participants using the Kappa statistic to measure concordance between codes independently coded by two research staff. Results: There were 767 diaries collected at baseline and event details from 563 injuries and exposure details from injury crossover periods. There were no event, location, or activity details which could not be coded using the ICECI. Kappa statistics for concordance between raters within each of the dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for activity and location in the control periods. Discussion: This study represents the first detailed account of the properties of the ICECI revealed by its use in a primary analytic epidemiological study of injury prevention. The results of this study provide considerable support for the ICECI and its further use.

From the cathedral to the classroom : the emergence of new discourses on religious education

In 2009, Religious Education is a designated key learning area in Catholic schools in the Archdiocese of Brisbane and, indeed, across Australia. Over the years, though, different conceptualisations of the nature and purpose of religious education have led to the construction of different approaches to the classroom teaching of religion. By investigating the development of religious education policy in the Archdiocese of Brisbane from 1984 to 2003, the study seeks to trace the emergence of new discourses on religious education. The study understands religious education to refer to a lifelong process that occurs through a variety of forms (Moran, 1989). In Catholic schools, it refers both to co-curricula activities, such as retreats and school liturgies, and the classroom teaching of religion. It is the policy framework for the classroom teaching of religion that this study explores. The research was undertaken using a policy case study approach to gain a detailed understanding of how new conceptualisations of religious education emerged at a particular site of policy production, in this case, the Archdiocese of Brisbane. The study draws upon Yeatman’s (1998) description of policy as occurring “when social actors think about what they are doing and why in relation to different and alternative possible futures” (p. 19) and views policy as consisting of more than texts themselves. Policy texts result from struggles over meaning (Taylor, 2004) in which specific discourses are mobilised to support particular views. The study has a particular interest in the analysis of Brisbane religious education policy texts, the discursive practices that surrounded them, and the contexts in which they arose. Policy texts are conceptualised in the study as representing “temporary settlements” (Gale, 1999). Such settlements are asymmetrical, temporary and dependent on context: asymmetrical in that dominant actors are favoured; temporary because dominant actors are always under challenge by other actors in the policy arena; and context - dependent because new situations require new settlements. To investigate the official policy documents, the study used Critical Discourse Analysis (hereafter referred to as CDA) as a research tool that affords the opportunity for researchers to map and chart the emergence of new discourses within the policy arena. As developed by Fairclough (2001), CDA is a three-dimensional application of critical analysis to language. In the Brisbane religious education arena, policy texts formed a genre chain (Fairclough, 2004; Taylor, 2004) which was a focus of the study. There are two features of texts that form genre chains: texts are systematically linked to one another; and, systematic relations of recontextualisation exist between the texts. Fairclough’s (2005) concepts of “imaginary space” and “frameworks for action” (p. 65) within the policy arena were applied to the Brisbane policy arena to investigate the relationship between policy statements and subsequent guidelines documents. Five key findings emerged from the study. First, application of CDA to policy documents revealed that a fundamental reconceptualisation of the nature and purpose of classroom religious education in Catholic schools occurred in the Brisbane policy arena over the last twenty-five years. Second, a disjuncture existed between catechetical discourses that continued to shape religious education policy statements, and educational discourses that increasingly shaped guidelines documents. Third, recontextualisation between policy documents was evident and dependent on the particular context in which religious education occurred. Fourth, at subsequent links in the chain, actors created their own “imaginary space”, thereby altering orders of discourse within the policy arena, with different actors being either foregrounded or marginalised. Fifth, intertextuality was more evident in the later links in the genre chain (i.e. 1994 policy statement and 1997 guidelines document) than in earlier documents. On the basis of the findings of the study, six recommendations are made. First, the institutional Church should carefully consider the contribution that the Catholic school can make to the overall pastoral mission of the diocese in twenty-first century Australia. Second, policymakers should articulate a nuanced understanding of the relationship between catechesis and education with regard to the religion classroom. Third, there should be greater awareness of the connections among policies relating to Catholic schools – especially the connection between enrolment policy and religious education policy. Fourth, there should be greater consistency between policy documents. Fifth, policy documents should be helpful for those to whom they are directed (i.e. Catholic schools, teachers). Sixth, “imaginary space” (Fairclough, 2005) in policy documents needs to be constructed in a way that allows for multiple “frameworks for action” (Fairclough, 2005) through recontextualisation. The findings of this study are significant in a number of ways. For religious educators, the study highlights the need to develop a shared understanding of the nature and purpose of classroom religious education. It argues that this understanding must take into account the multifaith nature of Australian society and the changing social composition of Catholic schools themselves. Greater recognition should be given to the contribution that religious studies courses such as Study of Religion make to the overall religious development of a person. In view of the social composition of Catholic schools, there is also an issue of ecclesiological significance concerning the conceptualisation of the relationship between the institutional Catholic Church and Catholic schools. Finally, the study is of significance because of its application of CDA to religious education policy documents. Use of CDA reveals the foregrounding, marginalising, or excluding of various actors in the policy arena.

Everyday life and the edges of existence : wrongs with no name or the wrong name?

Actions for wrongful life, as they have come unfortunately to be styled, encompass various types of claim. These include claims for alleged negligence after conception, those based on negligent advice or diagnosis prior to conception concerning possible effects of treatment given to the child's mother, contraception or sterilisation, or genetic disability. This distinguishes such claims from those for so called wrongful birth, which are claims by parents for the cost of raising either a healthy or a disabled child where the unplanned birth imposes costs on the parents as a result of clinical negligence. Two of the more controversial cases to have reached the High Court of Australia which are if interest to us here in the past decade are Cattanach v Melchior where the court, by a narrow majority (McHugh, Gummow, Kirby and Callinan JJ; Gleeson CJ, Hayne and Heydon dissenting) acknowledged recovery for wrongful birth. In the second joined appeals of Harriton v Stephens and Waller v James; Waller v Hoolahan the court overwhelmingly precluded a ‘wrongful life’ claim (Gleeson CJ, Gummow, Hayne, Callinan, Heydon and Crennan JJ; Kirby J dissenting). Both cases raised issues around the sanctity and value of life and the nature of harm and the assessment of damages, and this brief note affords us the opportunity to consider the way in which the ‘life as legal loss’ arguments were treated by the various judges in both cases.

The contribution of physical activity and sedentary behaviours to the growth and development of children and adolescents : implications for overweight and obesity

The obesity epidemic is a global trend and is of particular concern in children. Recent reports have highlighted the severity of obesity in children by suggesting: “today's generation of children will be the first for over a century for whom life expectancy falls.” This review assesses the evidence that identifies the important role of physical activity in the growth, development and physical health of young people, owing to its numerous physical and psychological health benefits. Key issues, such as “does a sedentary lifestyle automatically lead to obesity” and “are levels of physical activity in today's children less than physical activity levels in children from previous generations?”, are also discussed. Today's environment enforces an inactive lifestyle that is likely to contribute to a positive energy balance and childhood obesity. Whether a child or adolescent, the evidence is conclusive that physical activity is conducive to a healthy lifestyle and prevention of disease. Habitual physical activity established during the early years may provide the greatest likelihood of impact on mortality and longevity. It is evident that environmental factors need to change if physical activity strategies are to have a significant impact on increasing habitual physical activity levels in children and adolescents. There is also a need for more evidence-based physical activity guidelines for children of all ages. Efforts should be concentrated on facilitating an active lifestyle for children in an attempt to put a stop to the increasing prevalence of obese children

The effect of graded levels of exercise on energy intake and balance in free-living men, consuming their normal diet

Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ~1.6 MJ/day) and high exercise level (Hex; ~3.2 MJ/day). On days 1-2 subjects were given a medium fat (MF) maintenance diet (1.6 ´ resting metabolic rate (RMR)). Measurements: On days 3-9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P<0.001 (s.e.d=0.55)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 11.6, 11.8 and 11.8 MJ/day (F(2,10)=0.10; P=0.910 (s.e.d.=0.10)), respectively. There were no treatment effects on hunger, appetite or body weight, but there was evidence of weight loss on the Hex treatment. Conclusion: Increasing EE did not lead to compensation of EI over 7 days. However, total daily EE tended to decrease over time on the two exercise treatments. Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI.

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized stsytems for temporal tracking of appetite ratings.

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more arti®cial) conditions of the laboratory where the signal : noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a signi®cantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably