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.

3-D reconstruction of an ancient Egyptian mummy using X-ray computer tomography

Computer tomography has been used to image and reconstruct in 3-D an Egyptian mummy from the collection of the British Museum. This study of Tjentmutengebtiu, a priestess from the 22nd dynasty (945-715 BC) revealed invaluable information of a scientific, Egyptological and palaeopathological nature without mutilation and destruction of the painted cartonnage case or linen wrappings. Precise details on the removal of the brain through the nasal cavity and the viscera from the abdominal cavity were obtained. The nature and composition of the false eyes were investigated. The detailed analysis of the teeth provided a much closer approximation of age at death. The identification of materials used for the various amulets including that of the figures placed in the viscera was graphically demonstrated using this technique.

Vitamin D in health and disease : an insight into traditional functions and new roles for the 'sunshine vitamin'

Vitamin D is unique among the vitamins in that humans can synthesize it via the action of UV radiation upon the skin. This combined with its ability to act on specific target tissues via Vitamin D Receptor’s (VDR) make its classification as a steroid hormone more appropriate. While Vitamin D deficiency is a recognized problem in some northern latitude countries, recent studies have shown even in sunny countries such as Australia, vitamin D deficiency may be more prevalent than first thought. Vitamin D is most well known for its role in bone health, however, the discovery of VDR’s on a wide variety of tissue types has also opened up roles for vitamin D far beyond traditional bone health. These include possible associations with autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, cancer, cardiovascular diseases and muscle strength. Firstly, this paper presents an overview of the two sources of vitamin D: exposure to ultraviolet-B radiation and food sources of vitamin D, with particular focus on both Australian and international studies on dietary vitamin D intake and national fortification strategies. Secondly, the paper reviews recent epidemiological and experimental evidence linking vitamin D and its role in health and disease for the major conditions linked to suboptimal vitamin D, while identifying significant gaps in the research and possible future directions for research.

Vitamin D and sun protection : the impact of mixed public health messages in Australia

Exposure of the skin to sunlight can cause skin cancer and is also necessary for cutaneous vitamin D production. Media reports have highlighted the purported health benefits of vitamin D. Our aim was to examine attitudes and behaviours related to sun protection and vitamin D. A cross-sectional study of 2,001 residents in Queensland, Australia aged 20-70 years was undertaken. Information collected included: skin cancer risk factors; perceptions about levels of sun exposure required to maintain vitamin D; belief that sun protection increases risk of vitamin D deficiency; intention, and actual change in sun protection practices for adults and children. Multivariate models examined predictors of attitudinal and behavioural change. One-third (32%) believed a fair-skinned adult, and 31% thought a child required at least 30 minutes per day in summer sun to maintain vitamin D levels. Reductions in sun protection were reported by 21% of adults and 14% of children. Factors associated with belief that sun protection may result in not obtaining enough vitamin D included aged ≥ 60 years (OR=1.35, 95% CI 1.09-1.66) and having skin that tanned easily (OR=1.96, 95% CI 1.38-2.78). Participants from low income households, and those who frequently used sun protective clothing were more likely to have reduced sun protection practices (OR=1.33, 95% CI 1.10-1.73 and OR=1.73, 95% CI 1.36-2.20, respectively). This study provides evidence of reductions in sun protection practices in a population living in a high UV environment. There is an urgent need to re-focus messages regarding sun exposure and for continued sun protection practices.

Describing ocular aberrations with wavefront vergence maps

A common optometric problem is to specify the eye’s ocular aberrations in terms of Zernike coefficients and to reduce that specification to a prescription for the optimum sphero-cylindrical correcting lens. The typical approach is first to reconstruct wavefront phase errors from measurements of wavefront slopes obtained by a wavefront aberrometer. This paper applies a new method to this clinical problem that does not require wavefront reconstruction. Instead, we base our analysis of axial wavefront vergence as inferred directly from wavefront slopes. The result is a wavefront vergence map that is similar to the axial power maps in corneal topography and hence has a potential to be favoured by clinicians. We use our new set of orthogonal Zernike slope polynomials to systematically analyse details of the vergence map analogous to Zernike analysis of wavefront maps. The result is a vector of slope coefficients that describe fundamental aberration components. Three different methods for reducing slope coefficients to a spherocylindrical prescription in power vector forms are compared and contrasted. When the original wavefront contains only second order aberrations, the vergence map is a function of meridian only and the power vectors from all three methods are identical. The differences in the methods begin to appear as we include higher order aberrations, in which case the wavefront vergence map is more complicated. Finally, we discuss the advantages and limitations of vergence map representation of ocular aberrations.

Zernike radial slope polynomials for wavefront reconstruction and refraction

Ophthalmic wavefront sensors typically measure wavefront slope, from which wavefront phase is reconstructed. We show that ophthalmic prescriptions (in power-vector format) can be obtained directly from slope measurements without wavefront reconstruction. This is achieved by fitting the measurement data with a new set of orthonormal basis functions called Zernike radial slope polynomials. Coefficients of this expansion can be used to specify the ophthalmic power vector using explicit formulas derived by a variety of methods. Zernike coefficients for wavefront error can be recovered from the coefficients of radial slope polynomials, thereby offering an alternative way to perform wavefront reconstruction.

Building an effective trade practices commission : the role of Professor Robert Baxt AO

Bob Baxt, the third Chairman of the Trade Practices Commission, served for a single three year term from 1988 to 1991. He followed Bob McComas, who had deliberately adopted a non-litigious approach to preserving the competitive process, believing that he understood business as an insider and that much of what it did was not anti-competitive, when correctly viewed. Baxt was far more pro-active in his approach, and more closely aligned with that of the first Chairman, Ron Bannerman. Baxt sought to push the frontiers of investigation and precedent, and perhaps, more significantly, sought to influence his Ministers, the government, public servants and public opinion about the need to expand the coverage of the Trade Practices Act, increase penalties and properly resource the Commission so that it could perform its assigned roles. This article examines Baxt’s early and on-going role in teaching Australian students and professionals through his interdisciplinary Trade Practices Workshops, the political context of Baxt’s tenure, including his relations with the Attorney-General ,Michael Duffy, and his skilful handling of the Queensland Wire case.

Calculations of capacitive couplings in induction generators to analyse shaft voltage

This paper deals with the analysis of the parameters which are effective in shaft voltage generation of induction generators. It focuses on different parasitic capacitive couplings by mathematical equations, finite element simulations and experiments. The effects of different design parameters have been studied on proposed capacitances and resultant shaft voltage. Some parameters can change proposed capacitive coupling such as: stator slot tooth, the gap between slot tooth and winding, and the height of the slot tooth, as well as the air gap between the rotor and the stator. This analysis can be used in a primary stage of a generator design to reduce motor shaft voltage and avoid additional costs of resultant bearing current mitigation.

The impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25-hydroxyvitamin D concentrations

Studies have examined the associations between cancers and circulating 25-hydroxyvitamin D [25(OH)D], but little is known about the impact of different laboratory practices on 25(OH)D concentrations. We examined the potential impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25(OH)D concentrations. Blood samples from 20 healthy volunteers underwent alternative laboratory procedures: four centrifuging times (2, 24, 72, and 96 h after blood draw); three types of collection tubes (red top serum tube, two different plasma anticoagulant tubes containing heparin or EDTA); and two types of assays (DiaSorin radioimmunoassay [RIA] and chemiluminescence immunoassay [CLIA/LIAISON®]). Log-transformed 25(OH)D concentrations were analyzed using the generalized estimating equations (GEE) linear regression models. We found no difference in 25(OH)D concentrations by centrifuging times or type of assay. There was some indication of a difference in 25(OH)D concentrations by tube type in CLIA/LIAISON®-assayed samples, with concentrations in heparinized plasma (geometric mean, 16.1 ng ml−1) higher than those in serum (geometric mean, 15.3 ng ml−1) (p = 0.01), but the difference was significant only after substantial centrifuging delays (96 h). Our study suggests no necessity for requiring immediate processing of blood samples after collection or for the choice of a tube type or assay.

Public health and clinical dilemmas resulting from imprecise vitamin D tests

Objective: To determine whether there are clinical and public health dilemmas resulting from the reproducibility of routine vitamin D assays. Methods: Blinded agreement studies were conducted in eight clinical laboratories using two commonly used assays to measure serum 25-hydroxyvitamin D (25(OH)D) levels in Australasia and Canada (DiaSorin Radioimmunoassay (RIA) and DiaSorin LIAISON® one). Results: Only one laboratory measured 25(OH)D with excellent precision. Replicate 25(OH)D measurements varied by up to 97% and 15% of paired results differed by more than 50%. Thirteen percent of subjects received one result indicating insufficiency [25-50 nmol/l] and another suggesting adequacy [>50 nmol/l]). Agreement ranged from poor to excellent for laboratories using the manual RIA, while the precision of the semi-automated Liaison® system was consistently poor. Conclusions: Recent interest in the relevance of vitamin D to human health has increased demand for 25(OH)D testing and associated costs. Our results suggest clinicians and public health authorities are making decisions about treatment or changes to public health policy based on imprecise data. Clinicians, researchers and policy makers should be made aware of the imprecision of current 25(OH)D testing so that they exercise caution when using these assays for clinical practice, and when interpreting the findings of epidemiological studies based on vitamin D levels measured using these assays. Development of a rapid, reproducible, accurate and robust assay should be a priority due to interest in populationbased screening programs and research to inform public health policy about the amount of sun exposure required for human health. In the interim, 25(OH)D results should routinely include a statement of measurement uncertainty.

Modeling corneal surfaces with three-dimensional basis functions

Purpose: To ascertain the effectiveness of object-centered three-dimensional representations for the modeling of corneal surfaces. Methods: Three-dimensional (3D) surface decomposition into series of basis functions including: (i) spherical harmonics, (ii) hemispherical harmonics, and (iii) 3D Zernike polynomials were considered and compared to the traditional viewer-centered representation of two-dimensional (2D) Zernike polynomial expansion for a range of retrospective videokeratoscopic height data from three clinical groups. The data were collected using the Medmont E300 videokeratoscope. The groups included 10 normal corneas with corneal astigmatism less than −0.75 D, 10 astigmatic corneas with corneal astigmatism between −1.07 D and 3.34 D (Mean = −1.83 D, SD = ±0.75 D), and 10 keratoconic corneas. Only data from the right eyes of the subjects were considered. Results: All object-centered decompositions led to significantly better fits to corneal surfaces (in terms of the RMS error values) than the corresponding 2D Zernike polynomial expansions with the same number of coefficients, for all considered corneal surfaces, corneal diameters (2, 4, 6, and 8 mm), and model orders (4th to 10th radial orders) The best results (smallest RMS fit error) were obtained with spherical harmonics decomposition which lead to about 22% reduction in the RMS fit error, as compared to the traditional 2D Zernike polynomials. Hemispherical harmonics and the 3D Zernike polynomials reduced the RMS fit error by about 15% and 12%, respectively. Larger reduction in RMS fit error was achieved for smaller corneral diameters and lower order fits. Conclusions: Object-centered 3D decompositions provide viable alternatives to traditional viewer-centered 2D Zernike polynomial expansion of a corneal surface. They achieve better fits to videokeratoscopic height data and could be particularly suited to the analysis of multiple corneal measurements, where there can be slight variations in the position of the cornea from one map acquisition to the next.

Elucidating the links between UV radiation and vitamin D synthesis : using an in vitro model

Ultraviolet radiation (UV) is the carcinogen that causes the most common malignancy in humans – skin cancer. However, moderate UV exposure is essential for producing vitaminDin our skin. VitaminDincreases the absorption of calcium from the diet, and adequate calcium is necessary for the building and maintenance of bones. Thus, low levels of vitamin D can cause osteomalacia and rickets and contribute to osteoporosis. Emerging evidence also suggests vitamin D may protect against falls, internal cancers, psychiatric conditions, autoimmune diseases and cardiovascular diseases. Since the dominant source of vitamin D is sunlight exposure, there is a need to understand what is a “balanced��� level of sun exposure to maintain an adequate level of vitamin D but minimise the risks of eye damage, skin damage and skin cancer resulting from excessive UV exposure. There are many steps in the pathway from incoming solar UV to the eventual vitamin D status of humans (measured as 25-hydroxyvitamin D in the blood), and our knowledge about many of these steps is currently incomplete. This project begins by investigating the levels of UV available for synthesising vitamin D, and how these levels vary across seasons, latitudes and times of the day. The thesis then covers experiments conducted with an in vitro model, which was developed to study several aspects of vitamin D synthesis. Results from the model suggest the relationship between UV dose and vitamin D is not linear. This is an important input into public health messages regarding ‘safe’ UV exposure: larger doses of UV, beyond a certain limit, may not continue to produce vitamin D; however, they will increase the risk of skin cancers and eye damage. The model also showed that, when given identical doses of UV, the amount of vitamin D produced was impacted by temperature. In humans, a temperature-dependent reaction must occur in the top layers of human skin, prior to vitamin D entering the bloodstream. The hypothesis will be raised that cooler temperatures (occurring in winter and at high latitudes) may reduce vitamin D production in humans. Finally, the model has also been used to study the wavelengths of UV thought to be responsible for producing vitamin D. It appears that vitamin D production is limited to a small range of UV wavelengths, which may be narrower than previously thought. Together, these results suggest that further research is needed into the ability of humans to synthesise vitamin D from sunlight. In particular, more information is needed about the dose-response relationship in humans and to investigate the proposed impact of temperature. Having an accurate action spectrum will also be essential for measuring the available levels of vitamin D-effective UV. As this research continues, it will contribute to the scientific evidence-base needed for devising a public health message that will balance the risks of excessive UV exposure with maintaining adequate vitamin D.

Devising a scenographic approach in Jonzi D's Hip Hop theatre

Jonzi D, one of the leading Hip Hop voices in the UK, creates contemporary theatrical works that merge dance, street art, original scored music and contemporary rap poetry, to create theatrical events that expand a thriving sense of a Hip Hop nation with citizens in the UK, throughout southern Africa and the rest of the world. In recent years Hip Hop has evolved as a performance genre in and of itself that not only borrows from other forms but vitally now contributes back to the body of contemporary practice in the performing arts. As part of this work Jonzi’s company Jonzi D Productions is committed to creating and touring original Hip Hop theatre that promotes the continuing development and awareness of a nation with its own language, culture and currency that exists without borders. Through the deployment of a universal voice from the local streets of Johannesburg and the East End of London, Jonzi D creates a form of highly energized performance that elevates Hip Hop as great democratiser between the highly developed global and under resourced local in the world. It is the staging of this democratised and technologised future (and present), that poses the greatest challenge for the scenographer working with Jonzi and his company, and the associated deprogramming and translation of the artists particular filmic vision to the stage, that this discussion will explore. This paper interrogates not only how a scenographic strategy can support the existence of this work but also how the scenographer as outsider can enter and influence this nation.

Sir Neville Howse (VC), Private John Simpson Kirkpatrick and Private Martin O’Meara (VC) and their contributions to Australian military medicine

Medical personnel serving with the Defence Forces have contributed to the evolution of trauma treatment and the advancement of prehospital care within the military environment. This paper investigates the stories of an Australian Medical Officer, Sir Neville Howse, and two stretcher bearers, Private John Simpson (Kirkpatrick) and Private Martin O’Meara, In particular it describes the gruelling conditions under which they performed their roles, and reflects on the legacy that they have left behind in Australian society. While it is widely acknowledged that conflicts such as World War One should never have happened, as civilian and defence force paramedics, we should never forget the service and sacrifice of defence force medical personnel and their contribution to the body of knowledge on the treatment of trauma. These men and women bravely provided emergency care in the most harrowing conditions possible. However, men like Martin O’Meara may not have been given the same status in society today as Sir Neville Howse or Simpson and his donkey, due to the public’s lack of awareness and acceptance of war neurosis and conditions such as post traumatic stress disorder, reactive psychosis and somatoform disorders which were suffered by many soldiers during their wartime service and on their return home after fighting in war.