Chronic pain and the use of complementary and alternative medicine in rural Victoria, Australia.

OBJECTIVE: The relationship between chronic pain and complementary and alternative medicine (CAM) use is poorly understood, and the situation in rural Australia is particularly unclear. The objective here was to determine the socio-demographic factors associated with the use of CAM for the treatment of chronic pain in a region of rural Australia. METHODS: This secondary analysis used data from a population health survey, Crossroads-II, to assess the relationships of various socio-demographic factors with the use of CAM by those suffering from chronic pain. DESIGN: Face-to-face surveys at households randomly selected from residential address lists. SETTING: A large regional centre and three nearby rural towns in northern Victoria, Australia. PARTICIPANTS: Sixteen years of age and older. MAIN OUTCOME MEASURES: Use of a CAM service to treat chronic pain. RESULTS: Being female (2.40 [1.47, 3.93], p < 0.001) and having a bachelor's degree (OR 2.24 [1.20, 4.20], p < 0.001) had a significant positive relationship with the use of CAM overall to redress chronic pain and those 50 years and older had greater odds of using manipulation therapies relative to those below 50 years (50-64: OR 0.52 [0.32, 0.86], p = 0.010; 65+: 0.37 [0.18, 0.75], p = 0.005). CONCLUSION: In the studied region, females and those with university education have the greatest odds of using CAM to treat chronic pain. This study needs to be complemented with more mechanistic investigations into the reasons people make the decisions they make about using CAM for the management of chronic pain.

New approaches narrow global species estimates for beetles, insects, and terrestrial arthropods.

It has been suggested that we do not know within an order of magnitude the number of all species on Earth [May RM (1988) Science 241(4872):1441-1449]. Roughly 1.5 million valid species of all organisms have been named and described [Costello MJ, Wilson S, Houlding B (2012) Syst Biol 61(5):871-883]. Given Kingdom Animalia numerically dominates this list and virtually all terrestrial vertebrates have been described, the question of how many terrestrial species exist is all but reduced to one of how many arthropod species there are. With beetles alone accounting for about 40% of all described arthropod species, the truly pertinent question is how many beetle species exist. Here we present four new and independent estimates of beetle species richness, which produce a mean estimate of 1.5 million beetle species. We argue that the surprisingly narrow range (0.9-2.1 million) of these four autonomous estimates--derived from host-specificity relationships, ratios with other taxa, plant:beetle ratios, and a completely novel body-size approach--represents a major advance in honing in on the richness of this most significant taxon, and is thus of considerable importance to the debate on how many species exist. Using analogous approaches, we also produce independent estimates for all insects, mean: 5.5 million species (range 2.6-7.8 million), and for terrestrial arthropods, mean: 6.8 million species (range 5.9-7.8 million), which suggest that estimates for the world's insects and their relatives are narrowing considerably.

Identification of Preferential Paths of Fossil Carbon within Water Resource Recovery Facilities via Radiocarbon Analysis.

The Intergovernmental Panel on Climate Change (IPCC) reported that all carbon dioxide (CO2) emissions generated by water resource recovery facilities (WRRFs) during treatment are modern, based on available literature. Therefore, such emissions were omitted from IPCC's greenhouse gas (GHG) accounting procedures. However, a fraction of wastewater's carbon is fossil in origin. We hypothesized that since the fossil carbon entering municipal WRRFs is mostly from soaps and detergents as dissolved organic matter, its fate can be selectively determined during the universally applied separation treatment processes. Analyzing radiocarbon at different treatment points within municipal WRRFs, we verified that the fossil content could amount to 28% in primary influent and showed varying distribution leaving different unit operations. We recorded the highest proportion of fossil carbon leaving the secondary treatment as off-gas and as solid sludge (averaged 2.08 kg fossil-CO2-emission-potential m-3 wastewater treated). By including fossil CO2, total GHG emission in municipal WRRFs increased 13%, and 23% if an on-site energy recovery system exists although much of the postdigestion fossil carbon remained in biosolids rather than in biogas, offering yet another carbon sequestration opportunity during biosolids handling. In comparison, fossil carbon contribution to GHG emission can span from negligible to substantial in different types of industrial WRRFs. With such a considerable impact, CO2 should be analyzed for each WRRF and not omitted from GHG accounting.

Zoonotic Transmission of Waterborne Disease: A Mathematical Model.

Waterborne parasites that infect both humans and animals are common causes of diarrhoeal illness, but the relative importance of transmission between humans and animals and vice versa remains poorly understood. Transmission of infection from animals to humans via environmental reservoirs, such as water sources, has attracted attention as a potential source of endemic and epidemic infections, but existing mathematical models of waterborne disease transmission have limitations for studying this phenomenon, as they only consider contamination of environmental reservoirs by humans. This paper develops a mathematical model that represents the transmission of waterborne parasites within and between both animal and human populations. It also improves upon existing models by including animal contamination of water sources explicitly. Linear stability analysis and simulation results, using realistic parameter values to describe Giardia transmission in rural Australia, show that endemic infection of an animal host with zoonotic protozoa can result in endemic infection in human hosts, even in the absence of person-to-person transmission. These results imply that zoonotic transmission via environmental reservoirs is important.

Exposure factors for wastewater-irrigated Asian vegetables and a probabilistic rotavirus disease burden model for their consumption.

Many farmers in water-scarce regions of developing countries use wastewater to irrigate vegetables and other agricultural crops, a practice that may expand with climate change. There are a number of health risks associated with wastewater irrigation for human food crops, particularly with surface irrigation techniques common in the developing world. The World Health Organization (WHO) recommends using quantitative microbial risk assessment (QMRA) to determine if the irrigation scheme meets health standards. However, only a few vegetables have been studied for wastewater risk and little information is known about the disease burden of wastewater-irrigated vegetable consumption in China. To bridge this knowledge gap, an experiment was conducted to determine volume of water left on Asian vegetables and lettuce after irrigation. One hundred samples each of Chinese chard (Brassica rapa var. chinensis), Chinese broccoli (Brassica oleracea var. alboglabra), Chinese flowering cabbage (Brassica rapa var. parachinensis), and lettuce (Lactuca sativa) were harvested after overhead sprinkler irrigation. Chinese broccoli and flowering cabbage were found to capture the most water and lettuce the least. QMRAs were then constructed to estimate rotavirus disease burden from consumption of wastewater-irrigated Asian vegetables in Beijing. Results indicate that estimated risks from these reuse scenarios exceed WHO guideline thresholds for acceptable disease burden for wastewater use, signifying that reduction of pathogen concentration or stricter risk management is necessary for safe reuse. Considering the widespread practice of wastewater irrigation for food production, particularly in developing countries, incorporation of water retention factors in QMRAs can reduce uncertainty regarding health risks for consumers worldwide.

Estimating global arthropod species richness: refining probabilistic models using probability bounds analysis.

A key challenge in the estimation of tropical arthropod species richness is the appropriate management of the large uncertainties associated with any model. Such uncertainties had largely been ignored until recently, when we attempted to account for uncertainty associated with model variables, using Monte Carlo analysis. This model is restricted by various assumptions. Here, we use a technique known as probability bounds analysis to assess the influence of assumptions about (1) distributional form and (2) dependencies between variables, and to construct probability bounds around the original model prediction distribution. The original Monte Carlo model yielded a median estimate of 6.1 million species, with a 90 % confidence interval of [3.6, 11.4]. Here we found that the probability bounds (p-bounds) surrounding this cumulative distribution were very broad, owing to uncertainties in distributional form and dependencies between variables. Replacing the implicit assumption of pure statistical independence between variables in the model with no dependency assumptions resulted in lower and upper p-bounds at 0.5 cumulative probability (i.e., at the median estimate) of 2.9-12.7 million. From here, replacing probability distributions with probability boxes, which represent classes of distributions, led to even wider bounds (2.4-20.0 million at 0.5 cumulative probability). Even the 100th percentile of the uppermost bound produced (i.e., the absolutely most conservative scenario) did not encompass the well-known hyper-estimate of 30 million species of tropical arthropods. This supports the lower estimates made by several authors over the last two decades.

Tracking type specific prevalence of human papillomavirus in cervical pre-cancer: a novel sampling strategy.

BACKGROUND: Surveillance designed to detect changes in the type-specific distribution of HPV in cervical intraepithelial neoplasia grade 3 (CIN-3) is necessary to evaluate the effectiveness of the Australian vaccination programme on cancer causing HPV types. This paper develops a protocol that eliminates the need to calculate required sample size; sample size is difficult to calculate in advance because HPV's true type-specific prevalence is imperfectly known. METHOD: A truncated sequential sampling plan that collects a variable sample size was designed to detect changes in the type-specific distribution of HPV in CIN-3. Computer simulation to evaluate the accuracy of the plan at classifying the prevalence of an HPV type as low (< 5%), moderate (5-15%), or high (> 15%) and the average sample size collected was conducted and used to assess its appropriateness as a surveillance tool. RESULTS: The plan classified the proportion of CIN-3 lesions positive for an HPV type very accurately, with >90% of simulations correctly classifying a simulated data-set with known prevalence. Misclassifying an HPV type of high prevalence as being of low prevalence, arguably the most serious kind of potential error, occurred < 0.05 times per 100 simulations. A much lower sample size (21-22 versus 40-48) was required to classify samples of high rather than low or moderate prevalence. CONCLUSIONS: Truncated sequential sampling enables the proportion of CIN-3 due to an HPV type to be accurately classified using small sample sizes. Truncated sequential sampling should be used for type-specific HPV surveillance in the vaccination era.

Quantifying uncertainty in estimation of tropical arthropod species richness.

There is a bewildering range of estimates for the number of arthropods on Earth. Several measures are based on extrapolation from species specialized to tropical rain forest, each using specific assumptions and justifications. These approaches have not provided any sound measure of uncertainty associated with richness estimates. We present two models that account for parameter uncertainty by replacing point estimates with probability distributions. The models predict medians of 3.7 million and 2.5 million tropical arthropod species globally, with 90% confidence intervals of [2.0, 7.4] million and [1.1, 5.4] million, respectively. Estimates of 30 million or greater are predicted to have <0.00001 probability. Sensitivity analyses identified uncertainty in the proportion of canopy arthropod species that are beetles as the most influential parameter, although uncertainties associated with three other parameters were also important. Using the median estimates suggests that in spite of 250 years of taxonomy and around 855,000 species of arthropods already described, approximately 70% await description.

MicroRNA in erythrocytes.

Mammalian erythrocytes are generally thought to lack RNA and therefore to be unable to translate new proteins in response to internal or external signals. Support for this long-standing view has accumulated from diverse studies, most of which have focused on the total content of RNA or the overall level of translation. However, more recent work on specific types of RNA has shown the presence in human erythrocytes of both Y RNA and microRNA. The latter seem particularly incongruous given that their normal role is to attenuate the translation of mRNA. Y RNA binds the Ro autoantigen which may have a role in cellular RNA quality control. Therefore the presence of both of these non-coding RNAs indicates the possible existence of other cryptic RNAs in erythrocytes. It also suggests either the existence of low levels of translation or new uncharacterized processes involving microRNA in these cells.

Cocoa Pod Borer (Conopomorpha cramerella Snellen) in Papua New Guinea: biosecurity models for New Ireland and the autonomous region of Bougainville.

Cocoa Pod Borer (Conopomorpha cramerella Snellen) (CPB) is an important pest of cocoa. Following its emergence as a pest in East New Britain, Papua New Guinea, in 2006, it was considered relevant to assess its potential spread to other cocoa growing regions. Its likelihood of introduction to the islands of Bougainville and New Ireland from East New Britain Province, Papua New Guinea, was modeled using Monte Carlo simulation. This dispersal model was based around different scenarios, identifying trends rather than explicitly attempting to encapsulate true values. The model suggested that CPB is far more likely to establish on New Ireland than on Bougainville. More important, incertitude resulting from incomplete knowledge of the amount and frequency of cocoa transported between islands had a significant effect on model outputs. Quarantine and agriculture officials will be able to refine these parameter values, and then use the relevant scenarios from those presented here as a guide to develop quarantine procedures. In addition, a contingency model was employed to estimate the optimal sampling effort to use following an incursion of CPB into Bougainville or New Ireland and the seemingly successful implementation of an initial eradication program. The model suggests that at a 1% infestation level, sampling should continue for 2.5-2.7 years (90% CI) after claiming eradication, and this estimate changed little for higher infestation levels. Through modeling variations in sampling intensity, the model also suggested that determining the full spread of CPB is more important than increased sampling within one region.

Involvement of extracellular matrix proteins in the course of experimental paracoccidioidomycosis.

We aimed at determining involvement of extracellular matrix proteins (ECMp) and an ECM-binding adhesin (32-kDa protein) from Paracoccidioides brasiliensis, in the course of experimental paracoccidioidomycosis. BALB/c mice were infected with P. brasiliensis conidia previously incubated with soluble laminin, fibronectin and fibrinogen or a mAb against the fungal adhesin. Inflammatory response, chitin levels and cytokine production at different postinfection periods were determined. Chitin was significantly decreased in lungs of mice infected with ECMp-treated conidia when compared with controls at week 8, especially with laminin and fibrinogen. Contrariwise, when animals were infected with mAb-treated conidia no differences in chitin content were found. The observed inflammatory reaction in lungs was equivalent in all cases. IFN-gamma increased significantly in lungs from mice infected with soluble ECMp - (at day 4 and week 12) or mAb-treated conidia (at week 12) when compared with animals infected with untreated conidia. Significant increased levels of tumour necrosis factor-alpha were observed at 8 weeks in animals infected with ECMp-treated conidia while no differences were observed during the remaining periods. These findings point toward an inhibitory effect of ECMp on P. brasiliensis conidia infectivity and suggest that these proteins may interfere with conidia initial adhesion to host tissues probably modulating the immune response in paracoccidioidomycosis.

Risk stratification of chest pain patients in the emergency department by a nurse utilizing a point of care protocol.

OBJECTIVE: Risk stratification of patients with ischaemic type chest pain assessed in the emergency department utilizing a point of care (POC) protocol. METHODS: Patient demographics, cardiac biomarkers, management and follow-up at 6 months were reviewed for patients seen over 20 months. RESULTS: Out of 546 patients, 351 (64%) were admitted. The diagnoses after admission were confirmed as acute myocardial infarction in 59 patients and unstable angina, (cTroponin T<0.09 ng/ml) in 92 patients. The c-statistic of the receiver operating curves for myocardial infarction (myocardial infarction, cTroponinT at 12 h >0.09 ng/ml) as determined by the POC assay was cTroponin I=0.884, CK-MB=0.883, myoglobin=0.845 and beta-type natriuretic peptide (BNP)=0.755. The c-statistic for the same sample assessed by the hospital laboratory was cTroponin T=0.893: for CK-MB within 12 h of admission it was 0.918; the 12 h cTroponin T was 0.982 and within 24 h of admission NT pro-BNP was 0.789. POC BNP in patients admitted was 68 ng/l (median) vs. 24 ng/l (median) for those not admitted, (P<0.001). POC BNP for patients admitted with unstable angina (12 h cTroponin T <0.09 ng/ml) was 47 ng/l (median, P<0.001). At 6 months, 14 patients had died; five during admission, two within 30 days and seven up to 6 months. During admission two died from heart failure, two with respiratory tract infection and one from carcinoma. Of those not admitted one had died from asbestosis. CONCLUSION: Risk stratification by a specialist nurse utilizing a POC protocol is an appropriate means of assessing patients with chest pain.

Abscopal Effect after Radiosurgery for Solitary Brain Metastasis from Non-small Cell Lung Cancer.

The abscopal effect is a phenomenon relating to the treatment of metastatic cancer in which localized irradiation to a tumor concurrently causes shrinkage of tumors distant from the area of treatment. Localized radiotherapy is thought to cause anti-tumor immunologic responses that lead to regression and remission of cancers distant to the initial location of treatment. We present a 47-year-old male with brain metastasis from non-small cell lung cancer (NSCLC) who went into remission following stereotactic radiosurgery treatment to a brain lesion, in the absence of systemic treatment. We discuss the novelty of this case and its importance to future research on the abscopal effect. Though it is difficult to distinguish the abscopal effect from spontaneous remission of non-targeted cancer, this report sheds insight on the potential for improving treatment for the leading cause of cancer death worldwide.

A transgene with repeated DNA causes high frequency, post-transcriptional suppression of ACC-oxidase gene expression in tomato.

Gene silencing with sense genes is an important method for down-regulating the expression of endogenous plant genes, but the frequency of silencing is unpredictable. Fifteen per cent of tomato plants transformed with a 35S-ACC-oxidase ( ACO 1) sense gene had reduced ACC-oxidase activity. However, 96% of plants transformed with an ACC-oxidase sense gene, containing two additional upstream inverted copies of its 5' untranslated region, exhibited reduced ACC-oxidase activity compared to wild-type plants. In the three plants chosen for analysis, there were substantially reduced amounts of both endogenous and transgenic ACO RNA, indicating that this was an example of co-suppression. Ribonuclease protection assays using probes spanning intron-exon borders showed that the reduced accumulation of endogenous ACO mRNA occurred post-transcriptionally since the abundance of unprocessed transcripts was not affected. The ACO1 transgene with the repeated 5'UTR also strongly inhibited the accumulation of RNA from the related ACO 2 gene in flowers, although there is little homology between the 5'UTRs of ACO 1 and ACO 2. These results indicate that although repeated DNA in a transgene greatly enhances the probability of gene silencing of an endogenous gene, it also involves generation of a trans -acting silencing signal produced, at least partly, from sequences external to the repeat.

Intravascular ultrasound molecular imaging of atheroma components in vivo.

OBJECTIVES: Our purpose was to quantitate and confirm specific echogenic immunoliposome (ELIP) atheroma component enhancement in vivo. BACKGROUND: Targeted ELIPs for ultrasonic detection and staging of active molecular components of endothelium and atheroma have been developed. METHODS: In Yucatan miniswine, the endothelium was injured from one femoral and one carotid artery, and animals were fed a high-cholesterol diet for two months to create various stages of atheroma. Arteries were imaged with intravascular ultrasound (IVUS) 5 and 10 min after ELIP injection (5-mg dose). Anti-intercellular adhesion molecule-1 (ICAM-1), anti-vascular cell adhesion molecule-1 (VCAM-1), anti-fibrin, anti-fibrinogen, and anti-tissue factor (TF) conjugated ELIPs were used, and immunohistochemistry (IHC) confirmed the presence or absence of molecular expression. Two blinded observers determined if each segment was enhanced by ELIP. Three-dimensional image reconstruction and videodensitometric analysis determined the mean gray-scale (MGS) change of the luminal border. RESULTS: To determine endothelial injury component enhancement, anti-fibrinogen ELIP enhanced exposed fibrin in all arteries (MGS increased 22 +/- 5%; 6 arteries; 2 animals). To determine enhancement of molecular components in atherosclerotic arteries, observers detected enhancement 5 min after anti-VCAM, anti-ICAM, anti-TF, anti-fibrin, and anti-fibrinogen conjugated ELIPs. Furthermore, ELIP enhanced atheroma MGS by 39 +/- 18% (n = 8). The IHC staining confirmed the expression of respective molecular targets in all enhanced segments. CONCLUSIONS: It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.

Regional material property alterations in porcine femoral arteries with atheroma development.

We have developed a novel methodology that permits assessment of regional vascular mechanical property alterations in the presence of atheroma in vivo employing a Yucatan miniswine model with induced lesions. Femoral arteries were imaged with intravascular ultrasound. Image data were segmented and, following three-dimensional reconstruction, underwent finite element and sensitivity analysis with optimization to identify regions with altered vascular mechanical properties. All regions were compared to histological analysis. In 12 animals with 8 weeks of endothelial cell denudation and high cholesterol diet (induced atherosclerosis), the elastic modulus initially decreased with early lesion development and then increased with increasing fibrosis-(elastic modulus-all values x10(4)Pa-mean+/-SEM) histologically normal (non-denuded control segment) elements 9.73+/-0.01, fatty elements 9.53+/-0.01, fibrofatty elements 9.41+/-0.03, and fibrous elements 9.68+/-0.02 (all p<0.001 vs. normal elements). Wall thickness, however, increased with atheroma formation. These data demonstrate decreasing vascular material properties with early lesions, followed by an increase as lesions progress. This methodology permits determination of areas with early atheroma development, follow atheroma progression, and potentially evaluate interventions aimed at decreasing atheroma load and normalizing vascular material properties.

Porcine carotid arterial material property alterations with induced atheroma: an in vivo study.

OBJECTIVE: A novel methodology has been developed to evaluate regional alterations in arterial wall material properties with induced atheroma in an animal model. METHODS: Atheromatous lesions (fatty, fibro-fatty, and fibrous) were induced in the carotid arteries of a Yucatan miniswine model by endothelial cell denudation and high cholesterol diet. The images at base line and 8 weeks after denudation were obtained using intravascular ultrasound (IVUS) imaging along with hemodynamic data. Finite element analysis (FEA) along with optimization was employed to assess regional alterations in elastic modulus in the presence of atheroma confirmed by histology. RESULTS: In animals with 8 weeks of induced atherosclerosis, the elastic modulus increased-(elastic modulus-all values x 10(4) Pa, mean+/-S.D.) normal elements (9.34+/-0.36) compared to abnormal elements (9.52+/-0.36) (p<0.05 versus normal elements). Wall thickness increased with atheroma formation. These data demonstrate stiffening vascular wall elastic modulus with lesion progression. This is different from the behavior of femoral arteries, where the elastic modulus decreases with early stages of atheroma development followed by an increase as lesions progress. CONCLUSIONS: This methodology permits determination of areas with early atheroma development, follow atheroma progression, and potentially evaluate interventions aimed at decreasing atheroma load and normalizing vascular material properties.

Assessment of public health risk associated with viral contamination in harvested urban stormwater for domestic applications.

Capturing stormwater is becoming a new standard for sustainable urban stormwater management, which can be used to supplement water supply portfolios in water-stressed cities. The key advantage of harvesting stormwater is to use low impact development (LID) systems for treatment to meet water quality requirement for non-potable uses. However, the lack of scientific studies to validate the safety of such practice has limited its adoption. Microbial hazards in stormwater, especially human viruses, represent the primary public health threat. Using adenovirus and norovirus as target pathogens, we investigated the viral health risk associated with a generic scenario of urban stormwater harvesting practice and its application for three non-potable uses: 1) toilet flushing, 2) showering, and 3) food-crop irrigation. The Quantitative Microbial Risk Assessment (QMRA) results showed that food-crop irrigation has the highest annual viral infection risk (median range: 6.8×10(-4)-9.7×10(-1) per-person-per-year or pppy), followed by showering (3.6×10(-7)-4.3×10(-2)pppy), and toilet flushing (1.1×10(-7)-1.3×10(-4)pppy). Disease burden of each stormwater use was ranked in the same order as its viral infection risk: food-crop irrigation>showering>toilet flushing. The median and 95th percentile risk values of toilet-flushing using treated stormwater are below U.S. EPA annual risk benchmark of ≤10(-4)pppy, whereas the disease burdens of both toilet-flushing and showering are within the WHO recommended disease burdens of ≤10(-6)DALYspppy. However, the acceptability of showering risk interpreted based on the U.S. EPA and WHO benchmarks is in disagreement. These results confirm the safety of stormwater application in toilet flushing, but call for further research to fill the data gaps in risk modeling as well as risk benchmarks.