A threshold analysis of dengue transmission in terms of weather variables and imported dengue cases in Australia

Dengue virus (DENV) transmission in Australia is driven by weather factors and imported dengue fever (DF) cases. However, uncertainty remains regarding the threshold effects of high-order interactions among weather factors and imported DF cases and the impact of these factors on autochthonous DF. A time-series regression tree model was used to assess the threshold effects of natural temporal variations of weekly weather factors and weekly imported DF cases in relation to incidence of weekly autochthonous DF from 1 January 2000 to 31 December 2009 in Townsville and Cairns, Australia. In Cairns, mean weekly autochthonous DF incidence increased 16.3-fold when the 3-week lagged moving average maximum temperature was <32 °C, the 4-week lagged moving average minimum temperature was ≥24 °C and the sum of imported DF cases in the previous 2 weeks was >0. When the 3-week lagged moving average maximum temperature was ≥32 °C and the other two conditions mentioned above remained the same, mean weekly autochthonous DF incidence only increased 4.6-fold. In Townsville, the mean weekly incidence of autochthonous DF increased 10-fold when 3-week lagged moving average rainfall was ≥27 mm, but it only increased 1.8-fold when rainfall was <27 mm during January to June. Thus, we found different responses of autochthonous DF incidence to weather factors and imported DF cases in Townsville and Cairns. Imported DF cases may also trigger and enhance local outbreaks under favorable climate conditions.

A porcine deep dermal partial thickness burn model with hypertrophic scarring

We developed a reproducible model of deep dermal partial thickness burn injury in juvenile Large White pigs. The contact burn is created using water at 92 degrees C for 15s in a bottle with the bottom replaced with plastic wrap. The depth of injury was determined by a histopathologist who examined tissue sections 2 and 6 days after injury in a blinded manner. Upon creation, the circular wound area developed white eschar and a hyperaemic zone around the wound border. Animals were kept for 6 weeks or 99 days to examine the wound healing process. The wounds took between 3 and 5 weeks for complete re-epithelialisation. Most wounds developed contracted, purple, hypertrophic scars. On measurement, the thickness of the burned skin was approximately 1.8 times that of the control skin at week 6 and approximately 2.2 times thicker than control skin at 99 days after injury. We have developed various methods to assess healing wounds, including digital photographic analysis, depth of organising granulation tissue, immunohistochemistry, electron microscopy and tensiometry. Immunohistochemistry and electron microscopy showed that our porcine hypertrophic scar appears similar to human hypertrophic scarring. The development of this model allows us to test and compare different treatments on burn wounds.

Vibrational spectroscopic study of the sulphate mineral glaucocerinite (Zn,Cu)10Al6(SO4)3(OH)32⋅18H2O – a natural layered double hydroxide

We have studied the molecular structure of the mineral glaucocerinite (Zn,Cu)5Al3(SO4)1.5(OH)16�9(H2O) using a combination of Raman and infrared spectroscopy. The mineral is one of the hydrotalcite supergroup of natural layered double hydroxides. The Raman spectrum is characterised by an intense Raman band at 982 cm�1 with a low intensity band at 1083 cm�1. These bands are attributed to the sulphate symmetric and antisymmetric stretching mode. The infrared spectrum is quite broad with a peak at 1020 cm�1. A series of Raman bands at 546, 584, 602, 625 and 651 cm�1 are assigned to the m4 (SO4)2� bending modes. The observation of multiple bands provides evidence for the reduction in symmetry of the sulphate anion from Td to C2v or even lower symmetry. The Raman band at 762 cm�1 is attributed to a hydroxyl deformation mode associated with AlOH units. Vibrational spectroscopy enables aspects of the molecular structure of glaucocerinite to be determined.

Modelling the economic benefits of gold standard care for chronic wounds in a community setting

Chronic leg ulcers are costly to manage for health service providers. Although evidence-based care leads to improved healing rates and reduced costs, a significant evidence-practice gap is known to exist. Lack of access to specialist skills in wound care is one reason suggested for this gap. The aim of this study was to model the change to total costs and health outcomes under two versions of health services for patients with leg ulcers: routine health services for community-living patients; and care provided by specialist wound clinics. Mean weekly treatment and health services costs were estimated from participants’ data (n=70) for the twelve months prior to their entry to a study specialist wound clinic, and prospectively for 24 weeks after entry. For the retrospective phase mean weekly costs of care were $AU130.30 (SD $12.64) and these fell to $AU53.32 (SD $6.47) for the prospective phase. Analysis at a population level suggests if 10,000 individuals receive 12 weeks of specialist evidence-based care, the cost savings are likely to be AU$9,238,800. Significant savings could be made by the adoption of evidence-based care such as that provided by the community and outpatient specialist wound clinics in this study.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough

Background Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. Methods 50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was ‘cough resolution’ defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Results Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. Conclusion A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children.

Zymosan-induced inflammation stimulates neo-adipogenesis

Objective: To investigate the potential of inflammation to induce new adipose tissue formation in the in vivo environment. Methods and results: Using an established model of in vivo adipogenesis, a silicone chamber containing a Matrigel and fibroblast growth factor 2 (1 μg/ml) matrix was implanted into each groin of an adult male C57Bl6 mouse and vascularized with the inferior epigastric vessels. Sterile inflammation was induced in one of the two chambers by suspending Zymosan-A (ZA) (200-0.02 μg/ml) in the matrix at implantation. Adipose tissue formation was assessed at 6, 8, 12 and 24 weeks. ZA induced significant adipogenesis in an inverse dose-dependent manner (P<0.001). At 6 weeks adipose tissue formation was greatest with the lowest concentrations of ZA and least with the highest. Adipogenesis occurred both locally in the chamber containing ZA and in the ZA-free chamber in the contralateral groin of the same animal. ZA induced a systemic inflammatory response characterized by elevated serum tumour necrosis factor-α levels at early time points. Aminoguanidine (40 μg/ml) inhibited the adipogenic response to ZA-induced inflammation. Adipose tissue formed in response to ZA remained stable for 24 weeks, even when exposed to the normal tissue environment. Conclusions: These results demonstrate that inflammation can drive neo-adipogenesis in vivo. This suggests the existence of a positive feedback mechanism in obesity, whereby the state of chronic, low-grade inflammation, characteristic of the condition, may promote further adipogenesis. The mobilization and recruitment of a circulating population of adipose precursor cells is likely to be implicated in this mechanism.

Flupirtine enhances the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis

Objective Current treatments for cancer pain are often inadequate, particularly when metastasis to bone is involved. The addition to the treatment regimen of another drug that has a complementary analgesic effect may increase the overall analgesia without the necessity to increase doses, thus avoiding dose-related side effects. This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2–3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain. Design Syngeneic prostate cancer cells were injected into the right tibia of male Wistar rats under anesthesia. This led to expanding tumor within the bone in 2 weeks, together with the concurrent development of hyperalgesia to noxious heat. Paw withdrawal thresholds from noxious heat were measured before and after the maximum non-sedating doses of morphine and flupirtine given alone and in combinations. Dose-response curves for morphine (0.13–5.0 mg/kg ip) and flupirtine (1.25–10.0 mg/kg ip) given alone and in fixed-dose combinations were plotted and subjected to an isobolographic analysis. Results Both morphine (ED50 = 0.74 mg/kg) and flupirtine (ED50 = 3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation. Isobolographic analysis revealed that there was a synergistic interaction between flupirtine and morphine. Addition of flupirtine to morphine treatment improved morphine anti-hyperalgesia, and resulted in the reversal of cancer-induced heat hyperalgesia. Conclusions These results suggest that flupirtine in combination with morphine may be useful clinically to provide better analgesia at lower morphine doses in the management of pain caused by tumors growing in bone.

How does access to development finance shape our cities?

In market economies the built environment is largely the product of private sector property development. Property development is a high-risk entrepreneurial activity executing expensive projects with long gestation periods in an uncertain environment and into an uncertain future. Risk lies at the core of development: the developer manages the multiple risks of development and it is the capital injection and financing that is placed at risk. From the developer's perspective the search for development capital is a quest: to access more finance, over a longer term, with fewer conditions and at lower rates. From the supply angle, capital of various sources - banks, insurance companies, superannuation funds, accumulated firm profits, retail investors and private equity - is always seeking above market returns for limited risk. Property development presents one potentially lucrative, but risky, investment opportunity. Competition for returns on capital produces a continual dynamic evolution of methods for funding property developments. And thus the relationship between capital and development and the outcomes for the built environment are in a restless continual evolution. Little is documented about the ways development is financed in Australia and even less of the consequences for cities. Using publicly available data sources and examples of different development financing from Australian practice, this paper argues that different methods of financing development have different outcomes and consequences for the built environment. This paper also presents an agenda for further research into these themes.

An acute cough-specific quality of life questionnaire for children: Development and validation

Background Patient-relevant outcome measures are essential for high-quality clinical research, and quality-of-life (QoL) tools are the current standard. Currently, there is no validated children's acute cough-specific QoL questionnaire. Objective The objective of this study was to develop and validate the Parent-proxy Children's Acute Cough-specific QoL Questionnaire (PAC-QoL). Methods Using focus groups, a 48-item PAC-QoL questionnaire was developed and later reduced to 16 items by using the clinical impact method. Parents of children with a current acute cough (<2 weeks) at enrollment completed 2 validated cough score measures, the preliminary 48-item PAC-QoL, and 3 other questionnaires (the State Trait Anxiety Inventory [STAI], the Short-Form 8-item 24-hour recall Health Survey [SF-8], and the Depression, Anxiety, and Stress 21-item Scale [DASS21]). All measures were repeated on days 3 and 14. Results The median age of the 155 children enrolled was 2.3 years (interquartile range, 1.3-4.6). Median cough duration at enrollment was 3 days (interquartile range, 2-5). The reduced 16-item scale had high internal consistency (Cronbach α = 0.95). Evidence for repeatability and criterion validity was shown by significant correlations between the domains and total PAC-QoL scores and the SF-8 (r = −0.36 and −0.51), STAI (r = −0.27 and −0.39), and DASS21 (r = −0.32 and −0.41) scales on days 0 and 3, respectively. The final PAC-QoL questionnaire was sensitive to change over time, with changes significantly relating to changes in cough score measures (P < .001). Conclusion The 16-item PAC-QoL is a reliable and valid outcome measure that assesses QoL related to childhood acute cough at a given time point and reflects changes in acute cough-specific QoL over time.

Effect of tocopherol on atherosclerosis, vascular function and inflammation in Apolipoprotein E knockout mice with subtotal nephrectomy

Background/Aims: Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E−/− mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Methods: Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Results: Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10−7 M to 3 × 10−5 M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01). Conclusion: Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E−/− mouse with CKD.

Temporal and spatial patterns of seed dispersal of Musa acuminata by Cynopterus sphinx

The foraging behavior of greater short-nosed fruit bats (Cynopterus sphinx) on wild banana (Musa acuminata) and subsequent dispersal of seeds were studied in the Tropical Rainforest Conservation Area, Xishuangbanna Tropical Botanical Garden, Yunnan province, by direct observation of marked fruits, mist netting, and seed collection. The mean number (± SE) of individual C. sphinx captured by mist net were 2.2 ± 0.33/day and 1.4 ± 0.32/day in the rainy season (September to October) and dry season (November to December), respectively; the difference was not significant. The number of seed pellets expelled was 9.0 ± 1.12/day and 7.2 ± 1.37/day in the rainy and dry seasons respectively; again the difference was not significant. The removal curves for marked fruit were similar for 10 focal trees. Fruits were consumed heavily within two weeks after ripening and all the marked fruit were removed within one month. The difference in seed dispersal was significant between different feeding roosts indicating that patterns of seed dispersal may not be uniform. We found the seeds of M. acuminata can be dispersed by C. sphinx to a distance of about 200 m, and C. sphinx can be considered as an effective seed disperser of M. acuminata.

Streamlined research funding using short proposals and accelerated peer review : an observational study

Background Despite the widely recognised importance of sustainable health care systems, health services research remains generally underfunded in Australia. The Australian Centre for Health Services Innovation (AusHSI) is funding health services research in the state of Queensland. AusHSI has developed a streamlined protocol for applying and awarding funding using a short proposal and accelerated peer review. Method An observational study of proposals for four health services research funding rounds from May 2012 to November 2013. A short proposal of less than 1,200 words was submitted using a secure web-based portal. The primary outcome measures are: time spent preparing proposals; a simplified scoring of grant proposals (reject, revise or accept for interview) by a scientific review committee; and progressing from submission to funding outcomes within eight weeks. Proposals outside of health services research were deemed ineligible. Results There were 228 eligible proposals across 4 funding rounds: from 29% to 79% were shortlisted and 9% to 32% were accepted for interview. Success rates increased from 6% (in 2012) to 16% (in 2013) of eligible proposals. Applicants were notified of the outcomes within two weeks from the interview; which was a maximum of eight weeks after the submission deadline. Applicants spent 7 days on average preparing their proposal. Applicants with a ranking of reject or revise received written feedback and suggested improvements for their proposals, and resubmissions composed one third of the 2013 rounds. Conclusions The AusHSI funding scheme is a streamlined application process that has simplified the process of allocating health services research funding for both applicants and peer reviewers. The AusHSI process has minimised the time from submission to notification of funding outcomes.

Age-related changes to adenosine in rat coronary resistance vessels

1. The vasodilator effects of adenosine receptor agonists, isoprenaline and histamine were examined in perfused heart preparations from young (4–6 weeks) and mature (12–20 weeks) rats. 2. Adenosine induced a biphasic concentration-dependent decrease in KCl (35 mM) raised coronary perfusion pressure in hearts from young and mature rats, suggesting the presence of both high- and low-affinity sites for adenosine receptors in the two age groups tested. In heart preparations from mature rats, vasodilator responses to adenosine were significantly reduced compared with responses observed in young rats. 3. Responses to 5′-N-ethylcarboxamidoadenosine (NECA) and 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) were reduced in preparations from mature rats, whereas the vasodilator actions of N6-cyclopentyladenosine (CPA) and N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not change with age. 4. The results presented in this study suggest that several adenosine receptor subtypes mediate vasodilator responses in the coronary circulation of the rat and that a reduction in response to adenosine with age may be due to changes in the high-affinity receptor site.

The relationship between stress, HPA axis functioning and brain structure in first episode psychosis over the first 12 weeks of treatment

Stress and abnormal hypothalamic-pituitary-adrenal axis functioning have been implicated in the early phase of psychosis and may partly explain reported changes in brain structure. This study used magnetic resonance imaging to investigate whether biological measures of stress were related to brain structure at baseline and to structural changes over the first 12 weeks of treatment in first episode patients (n=22) compared with matched healthy controls (n=22). At baseline, no significant group differences in biological measures of stress, cortical thickness or hippocampal volume were observed, but a significantly stronger relationship between baseline levels of cortisol and smaller white matter volumes of the cuneus and anterior cingulate was found in patients compared with controls. Over the first 12 weeks of treatment, patients showed a significant reduction in thickness of the posterior cingulate compared with controls. Patients also showed a significant positive relationship between baseline cortisol and increases in hippocampal volume over time, suggestive of brain swelling in association with psychotic exacerbation, while no such relationship was observed in controls. The current findings provide some support for the involvement of stress mechanisms in the pathophysiology of early psychosis, but the changes are subtle and warrant further investigation.

Weight-related risk perception among healthy and overweight pregnant women: A cross-sectional study

Objective The objective of this study was to evaluate weight-related risk perception in early pregnancy and to compare this perception between women commencing pregnancy healthy weight and overweight. Study design Pregnant women (n=664) aged 29±5 (mean±s.d.) years were recruited from a metropolitan teaching hospital in Australia. A self-administered questionnaire was completed at around 16 weeks of gestation. Height measured at baseline and self-reported pre-pregnancy weight were used to calculate body mass index. Cross-sectional analysis was conducted. Differences between groups were assessed using chi-squared tests for categorical variables and t-tests or Mann–Whitney U tests for continuous variables depending on distribution. Result Excess gestational weight gain (GWG) during pregnancy was more important in leading to health problems for women or their child compared with pre-pregnancy weight. Personal risk perception for complications was low for all women, although overweight women had slightly higher scores than healthy-weight women (2.4±1.0 vs 2.9±1.0; P<0.001). All women perceived their risk for complications to be below that of an average pregnant woman. Conclusion Women should be informed of the risk associated with their pre-pregnancy weight (in the case of maternal overweight) and excess GWG. If efforts to raise risk awareness are to result in preventative action, this information needs to be accompanied by advice and appropriate support on how to reduce risk.