Evidence for an Auditory Fovea in the New Zealand Kiwi (Apteryx mantelli).

Kiwi are rare and strictly protected birds of iconic status in New Zealand. Yet, perhaps due to their unusual, nocturnal lifestyle, surprisingly little is known about their behaviour or physiology. In the present study, we exploited known correlations between morphology and physiology in the avian inner ear and brainstem to predict the frequency range of best hearing in the North Island brown kiwi. The mechanosensitive hair bundles of the sensory hair cells in the basilar papilla showed the typical change from tall bundles with few stereovilli to short bundles with many stereovilli along the apical-to-basal tonotopic axis. In contrast to most birds, however, the change was considerably less in the basal half of the epithelium. Dendritic lengths in the brainstem nucleus laminaris also showed the typical change along the tonotopic axis. However, as in the basilar papilla, the change was much less pronounced in the presumed high-frequency regions. Together, these morphological data suggest a fovea-like overrepresentation of a narrow high-frequency band in kiwi. Based on known correlations of hair-cell microanatomy and physiological responses in other birds, a specific prediction for the frequency representation along the basilar papilla of the kiwi was derived. The predicted overrepresentation of approximately 4-6 kHz matches potentially salient frequency bands of kiwi vocalisations and may thus be an adaptation to a nocturnal lifestyle in which auditory communication plays a dominant role.

Echolocation call production during aerial and terrestrial locomotion by New Zealand's enigmatic lesser short-tailed bat, Mystacina tuberculata

Linkage of echolocation call production with contraction of flight muscles has been suggested to reduce the energetic cost of flight with echolocation, such that the overall cost is approximately equal to that of flight alone. However, the pattern of call production with limb movement in terrestrially agile bats has never been investigated. We used synchronised high-speed video and audio recordings to determine patterns of association between echolocation call production and limb motion by Mystacina tuberculata Gray 1843 as individuals walked and flew, respectively. Results showed that there was no apparent linkage between call production and limb motion when bats walked. When in flight, two calls were produced per wingbeat, late in the downstroke and early in the upstroke. When bats walked, calls were produced at a higher rate, but at a slightly lower intensity, compared with bats in flight. These results suggest that M. tuberculata do not attempt to reduce the cost of terrestrial locomotion and call production through biomechanical linkage. They also suggest that the pattern of linkage seen when bats are in flight is not universal and that energetic savings cannot necessarily be explained by contraction of muscles associated with the downstroke alone.

The contribution of major depression to the global burden of ischemic heart disease : a comparative risk assessment

Background Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. Methods A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010. Results The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. Conclusions The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.

Estimating the burden of disease attributable to excess body weight in South Africa in 2000

Objective. To estimate the burden of disease attributable to excess body weight using the body mass index (BMI), by age and sex, in South Africa in 2000. Design. World Health Organization comparative risk assessment (CRA) methodology was followed. Re-analysis of the 1998 South Africa Demographic and Health Survey data provided mean BMI estimates by age and sex. Populationattributable fractions were calculated and applied to revised burden of disease estimates. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. Setting. South Africa. Subjects. Adults 30 years of age. Outcome measures. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, hypertensive disease, osteoarthritis, type 2 diabetes mellitus, and selected cancers. Results. Overall, 87% of type 2 diabetes, 68% of hypertensive disease, 61% of endometrial cancer, 45% of ischaemic stroke, 38% of ischaemic heart disease, 31% of kidney cancer, 24% of osteoarthritis, 17% of colon cancer, and 13% of postmenopausal breast cancer were attributable to a BMI 21 kg/m2. Excess body weight is estimated to have caused 36 504 deaths (95% uncertainty interval 31 018 - 38 637) or 7% (95% uncertainty interval 6.0 - 7.4%) of all deaths in 2000, and 462 338 DALYs (95% uncertainty interval 396 512 - 478 847) or 2.9% of all DALYs (95% uncertainty interval 2.4 - 3.0%). The burden in females was approximately double that in males. Conclusions. This study shows the importance of recognising excess body weight as a major risk to health, particularly among females, highlighting the need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of excess body weight.

Key influences on cycling for transport

Over recent years, the health, transport and environment sectors have been increasingly focused on the promotion of transport cycling. From a health perspective, transport cycling is recognised as a beneficial form of physical activity as it can be easily integrated into daily living, is done at an intensity that confers health benefits, and is associated with reductions in mortality and morbidity [1]. From a safety perspective, the risk of a serious cycling injury decreases as cycling increases [2] as having more cyclists on roads increases motor vehicle drivers’ awareness of cyclists and in turn makes cycling safer. Whereas cycling for recreation is the fourth most commonly reported physical activity among Australian adults [3], transport cycling is an underutilised travel mode. Approximately 1.3% of journeys to work in Australia are made by bicycle [4]. This low prevalence is mirrored in the UK and the US, but not in some European countries like the Netherlands and Denmark, where over 18% and 26%, respectively, of all journeys are made by bicycle [5]. In the past decade, concerted efforts have been made by Australian state and local governments to increase cycling rates [6]. Notably, Melbourne, Sydney and Brisbane have implemented policies, increased bicycle commuting infrastructure, and offered information and promotion programs to encourage commuter cycling [6,7]. Governments have also developed comprehensive longterm plans for guiding future cycling strategies, using lessons learned from around the world in developing successful cycling policy and promotion [6,7]. Changes in transport cycling rates in inner cities since these efforts have been implemented are encouraging. In Sydney, census data indicate an 83% increase in the number of people using a bicycle for commuting between 2001 and 2011 [8]. Counts of bicycles being ridden along major cycling commuter routes indicate increases in weekday morning cycling trips in Brisbane (63% increase from 2004 to 2010) [7] and in Melbourne (a 43% increase from 2006 to 2008) [9]. However, bicycle mode share to work has changed little: for example, between 2001 and 2011, it decreased slightly from 1.6% to 1.3% in Brisbane [10,11]. Researchers have been investigating factors that may be contributing to low rates of cycling for transport, to inform future policy and programming to encourage transport cycling. The aim of this paper is to overview our work to date in this area of research in Queensland.

A reduction of diffusion in PVA Fricke hydrogels

A modification to the PVA-FX hydrogel whereby the chelating agent, xylenol orange, was partially bonded to the gelling agent, poly-vinyl alcohol, resulted in an 8% reduction in the post irradiation Fe3+ diffusion, adding approximately 1 hour to the useful timespan between irradiation and readout. This xylenol orange functionalised poly-vinyl alcohol hydrogel had an OD dose sensitivity of 0.014 Gy−1 and a diffusion rate of 0.133 mm2 h−1. As this partial bond yields only incremental improvement, it is proposed that more efficient methods of bonding xylenol orange to poly-vinyl alcohol be investigated to further reduce the diffusion in Fricke gels.

Photon beam dose distributions for patients with implanted temporary tissue expanders

This study examines the effects of temporary tissue expanders (TTEs) on the dose distributions of photon beams in breast cancer radiotherapy treatments. EBT2 radiochromic film and ion chamber measurements were taken to quantify the attenuation and backscatter effects of the inhomogeneity. Results illustrate that the internal magnetic port present in a tissue expander causes a dose reduction of approximately 25% in photon tangent fields immediately downstream of the implant. It was also shown that the silicone elastomer shell of the tissue expander reduced the dose to the target volume by as much as 8%. This work demonstrates the importance for an accurately modelled high-density implant in the treatment planning system for post-mastectomy breast cancer patients.

Hydrological consequences of land-cover change: Quantifying the influence of plants on soil moisture with time-lapse electrical resistivity

Electrical resistivity of soils and sediments is strongly influenced by the presence of interstitial water. Taking advantage of this dependency, electrical-resistivity imaging (ERI) can be effectively utilized to estimate subsurface soil-moisture distributions. The ability to obtain spatially extensive data combined with time-lapse measurements provides further opportunities to understand links between land use and climate processes. In natural settings, spatial and temporal changes in temperature and porewater salinity influence the relationship between soil moisture and electrical resistivity. Apart from environmental factors, technical, theoretical, and methodological ambiguities may also interfere with accurate estimation of soil moisture from ERI data. We have examined several of these complicating factors using data from a two-year study at a forest-grassland ecotone, a boundary between neighboring but different plant communities.At this site, temperature variability accounts for approximately 20-45 of resistivity changes from cold winter to warm summer months. Temporal changes in groundwater conductivity (mean=650 S/cm =57.7) and a roughly 100-S/cm spatial difference between the forest and grassland had only a minor influence on the moisture estimates. Significant seasonal fluctuations in temperature and precipitation had negligible influence on the basic measurement errors in data sets. Extracting accurate temporal changes from ERI can be hindered by nonuniqueness of the inversion process and uncertainties related to time-lapse inversion schemes. The accuracy of soil moisture obtained from ERI depends on all of these factors, in addition to empirical parameters that define the petrophysical soil-moisture/resistivity relationship. Many of the complicating factors and modifying variables to accurately quantify soil moisture changes with ERI can be accounted for using field and theoretical principles.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Potentially inappropriate prescribing in older patients admitted to acute care hospitals and discharged to residential aged care facilities

Background The frequency of prescribing potentially inappropriate medications (PIMs) in older patients remains high regardless of the evidence of adverse outcomes from their use. This study aims to identify the prevalence and nature of PIMs at admission to acute care and at discharge to residential aged care facilities (RACFs) using the recently updated Beers’ Criteria. We also aim to identify if polypharmacy, age, gender and the frailty status of patients are independent risk factors for receiving a PIM. Methods This was a retrospective study of 206 patients discharged to RACFs from acute care. All patients were aged at least70 years and were admitted between July 2005 and May 2010; their admission and discharge medications were evaluated. Frailty status was measured as the Frailty Index (FI), adding each individual’s deficits and dividing by the total number of deficits considered, with FI 0.25 used as the cut-off between “fit” and “frail”. Results Mean patient age was 84.8 ± 6.7 years; the majority (57%) were older than 85 years and approximately 90% were frail. Patients were prescribed a mean of 7.2 regular medications at admission and 8.1 on discharge. At least one PIM was identified in 112 (54.4%) patients on admission and 102 (49.5%) patients on discharge. Of all medications prescribed at admission (1728), 10.8% were PIMs and at discharge of 1759 medications, 9.6% were PIMs. Of the total 187 PIMs on admission, 56 (30%) were stopped, and 131 were continued; 32 new PIMs were introduced. Commonly prescribed PIMs at both admission and discharge were central nervous system, cardiovascular and gastrointestinal drugs and analgesics. Of the potential risk factors, frailty status was the only significant predictor of PIMs at both admission and discharge (p = 0.016). Conclusion A high prevalence of unnecessary drug use was observed in frail older patients on admission to acute care hospitals and on discharge to RACFs. The only association with PIM use was the frailty status of patients. Further studies are needed to further evaluate this association.

The burden of cancer in member countries of the association of southeast asian nations (ASEAN)

This paper presents the most recent data on cancer rates and the burden of cancer in the ASEAN region. Epidemiological data were sourced from GLOBOCAN 2008 and disability adjusted life years (DALYs) lost were estimated using the standard methodology developed within the World Health Organization's Global Burden of Disease study. Overall, it was estimated there were over 700,000 new cases of cancer and 500,000 cancer deaths in ASEAN in the year 2008, leading to approximately 7.5 million DALYs lost in one year. The most commonly diagnosed cancers were lung (98,143), breast (86,842) and liver cancers (74,777). The most common causes of cancer death were lung cancer (85,772), liver cancer (69,115) and colorectal cancer (44,280). The burden of cancer in terms of DALYs lost was highest in Laos, Viet Nam and Myanmar and lowest in Brunei, Singapore and the Philippines. Significant differences in the patterns of cancer from country to country were observed. Another key finding was the major impact played by population age distribution on cancer incidence and mortality. Cancer rates in ASEAN are expected to increase with ageing of populations and changes in lifestyles associated with economic development. Therefore, ASEAN member countries are strongly encouraged to put in place cancer-control health carepolicies, focussed on strengthening the health systems to cope with projected increases in cancer prevention, treatment and management needs.

Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution

A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 A˚, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced "leopard skin"-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism.

Establishing the impact of temporary tissue expanders on electron and photon beam dose distributions

Purpose: This study investigates the effects of temporary tissue expanders (TTEs) on the dose distributions in breast cancer radiotherapy treatments under a variety of conditions. Methods: Using EBT2 radiochromic film, both electron and photon beam dose distribution measurements were made for different phantoms, and beam geometries. This was done to establish a more comprehensive understanding of the implant’s perturbation effects under a wider variety of conditions. Results: The magnetic disk present in a tissue expander causes a dose reduction of approximately 20% in a photon tangent treatment and 56% in electron boost fields immediately downstream of the implant. The effects of the silicon elastomer are also much more apparent in an electron beam than a photon beam. Conclusions: Evidently, each component of the TTE attenuates the radiation beam to different degrees. This study has demonstrated that the accuracy of photon and electron treatments of post-mastectomy patients is influenced by the presence of a tissue expander for various beam orientations. The impact of TTEs on dose distributions establishes the importance of an accurately modelled high-density implant in the treatment planning system for post-mastectomy patients.

A simulation model of the within-host dynamics of Plasmodium vivax infection

Background The benign reputation of Plasmodium vivax is at odds with the burden and severity of the disease. This reputation, combined with restricted in vitro techniques, has slowed efforts to gain an understanding of the parasite biology and interaction with its human host. Methods A simulation model of the within-host dynamics of P. vivax infection is described, incorporating distinctive characteristics of the parasite such as the preferential invasion of reticulocytes and hypnozoite production. The developed model is fitted using digitized time-series’ from historic neurosyphilis studies, and subsequently validated against summary statistics from a larger study of the same population. The Chesson relapse pattern was used to demonstrate the impact of released hypnozoites. Results The typical pattern for dynamics of the parasite population is a rapid exponential increase in the first 10 days, followed by a gradual decline. Gametocyte counts follow a similar trend, but are approximately two orders of magnitude lower. The model predicts that, on average, an infected naïve host in the absence of treatment becomes infectious 7.9 days post patency and is infectious for a mean of 34.4 days. In the absence of treatment, the effect of hypnozoite release was not apparent as newly released parasites were obscured by the existing infection. Conclusions The results from the model provides useful insights into the dynamics of P. vivax infection in human hosts, in particular the timing of host infectiousness and the role of the hypnozoite in perpetuating infection.

Social policy implications relating to road trauma in a rapidly motorising world : the example of China

The World Health Organization (WHO) identifies road trauma as a major public health issue in all countries, though most notably among low-to-middle income countries and particularly those experiencing rapid motorisation, such as China. As China transitions from a nation of bicycle riders and pedestrians to one where car ownership is increasingly desired, there is need to address the accompanying social policy challenges. With this increased motorisation has come an increased road trauma burden, shouldered disproportionately among the population. Vulnerable road users (i.e., pedestrians, cyclists, motorcyclists) are of primary concern because they are most frequently killed in road crashes, representing approximately 70% of all Chinese road-related fatalities. The aim of this paper is to summarise the scale of the road trauma burden, highlight the disparity of this burden across the Chinese population, and discuss the related social policy implications in dealing with the impact of deaths and of otherwise healthy lives diminished by injury and disability. Future research priorities are also discussed and include the need to strive to provide detailed information on the level of inequity of the road trauma burden across the population and identify appropriate social supports and healthcare services required, both preventative and post-crash, so these can be developed and implemented throughout China.