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.

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.

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.

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.

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.

A probabilistic quantitative microbial risk assessment model of norovirus disease burden from wastewater irrigation of vegetables in Shepparton, Australia.

Wastewater can be an important resource for water-scarce regions of the world, but a major barrier to its use is the associated health risk. Quantitative microbial risk assessment (QMRA) is a probabilistic modeling technique used to determine the health risks from wastewater reuse, but only a handful of QMRA studies have examined the norovirus health risks from consumption of vegetables irrigated with human wastewater, even though norovirus is a, if not the most, significant microbial cause of diarrheal disease world-wide. Furthermore, the majority of these studies have focused only on risks from lettuce consumption. To meet the knowledge gap in health risks for other vegetables, a QMRA model was constructed for agricultural wastewater irrigation in the regional city of Shepparton, Australia, using fecal shedding rates to estimate norovirus concentration in raw sewage. Annual norovirus disease burden was estimated for the consumption of lettuce, broccoli, cabbage, Asian vegetables, and cucumber after irrigation with treated wastewater. Results indicate that the waste stabilization pond treatment did not have sufficient virus removal to meet the World Health Organization (WHO) threshold for acceptable level of risk for wastewater reuse, but addition of disinfection treatments provided acceptable results for consumption of cucumber and broccoli. This is the first QMRA study to incorporate virus accumulation from previous wastewater irrigation events.

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.

Pathogen reduction requirements for direct potable reuse in Antarctica: evaluating human health risks in small communities.

Small, remote communities often have limited access to energy and water. Direct potable reuse of treated wastewater has recently gained attention as a potential solution for water-stressed regions, but requires further evaluation specific to small communities. The required pathogen reduction needed for safe implementation of direct potable reuse of treated sewage is an important consideration but these are typically quantified for larger communities and cities. A quantitative microbial risk assessment (QMRA) was conducted, using norovirus, giardia and Campylobacter as reference pathogens, to determine the level of treatment required to meet the tolerable annual disease burden of 10(-6) DALYs per person per year, using Davis Station in Antarctica as an example of a small remote community. Two scenarios were compared: published municipal sewage pathogen loads and estimated pathogen loads during a gastroenteritis outbreak. For the municipal sewage scenario, estimated required log10 reductions were 6.9, 8.0 and 7.4 for norovirus, giardia and Campylobacter respectively, while for the outbreak scenario the values were 12.1, 10.4 and 12.3 (95th percentiles). Pathogen concentrations are higher under outbreak conditions as a function of the relatively greater degree of contact between community members in a small population, compared with interactions in a large city, resulting in a higher proportion of the population being at risk of infection and illness. While the estimates of outbreak conditions may overestimate sewage concentration to some degree, the results suggest that additional treatment barriers would be required to achieve regulatory compliance for safe drinking water in small communities.

A probabilistic model of norovirus disease burden associated with greywater irrigation of home-produced lettuce in Melbourne, Australia.

The reuse of domestic greywater has become common in Australia, especially during periods of extreme drought. Greywater is typically used in a raw, untreated form, primarily for landscape irrigation, but more than a quarter of greywater users irrigate vegetable gardens with the water, despite government advice against this practice. Greywater can be contaminated with enteric pathogens and may therefore pose a health risk if irrigated produce is consumed raw. A quantitative microbial risk assessment (QMRA) model was constructed to estimate the norovirus disease burden associated with consumption of greywater-irrigated lettuce. The annual disease burdens (95th percentile; DALYs per person) attributed to greywater irrigation ranged from 2 × 10(-8) to 5 × 10(-4), depending on the source of greywater and the existence of produce washing within households. Accounting for the prevalence of produce-washing behaviours across Melbourne, the model predicted annual disease burdens ranging from 4 × 10(-9) for bathroom water use only to 3 × 10(-6) for laundry water use only, and accounting for the proportionate use of each greywater type, the annual disease burden was 2 × 10(-6). We recommend the preferential use of bathroom water over laundry water where possible as this would reduce the annual burden of disease to align with the current Australian recycled water guidelines, which recommend a threshold of 10(-6) DALYs per person. It is also important to consider other exposure pathways, particularly considering the high secondary attack rate of norovirus, as it is highly likely that the estimated norovirus disease burden associated with greywater irrigation of vegetables is negligible relative to household contact with an infected individual.

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.

Fixed sized samples for type-specific surveillance of human papillomavirus in genital warts.

Surveillance data suggest that human papillomavirus (HPV) vaccination in Australia is reducing the incidence of genital warts. However, existing surveillance measures do not assess the proportion of the remaining cases of warts that are caused by HPV types other than 6 or 11, against which the vaccine has no demonstrated effectiveness. Using computer simulation rather than sample size formulae, we established that genotyping at least 60 warts can accurately test whether the proportion of warts due to HPV types not targeted by the vaccine has increased (Type I error probability ≤ 0.05, Type II error probability <0.07). Standard formulae for calculating sample size, in contrast, suggest that a sample size of more than 130 would be required for this task, but using these formulae entails making several strong assumptions. Our methods require fewer assumptions and demonstrate that a smaller sample size than anticipated could be used to address the question of what proportion of post-vaccination cases of warts are due to nonvaccine types. In conjunction with indications of incidence and prevalence provided by existing surveillance measures, this could indicate the number of cases of post-vaccination warts due to nonvaccine types and hence whether type replacement is occurring.

Taking the "waste" out of "wastewater" for human water security and ecosystem sustainability.

Humans create vast quantities of wastewater through inefficiencies and poor management of water systems. The wasting of water poses sustainability challenges, depletes energy reserves, and undermines human water security and ecosystem health. Here we review emerging approaches for reusing wastewater and minimizing its generation. These complementary options make the most of scarce freshwater resources, serve the varying water needs of both developed and developing countries, and confer a variety of environmental benefits. Their widespread adoption will require changing how freshwater is sourced, used, managed, and priced.

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.

Antibody therapy for histoplasmosis.

The endemic human pathogenic fungus Histoplasma capsulatum is a major fungal pathogen with a broad variety of clinical presentations, ranging from mild, focal pulmonary disease to life-threatening systemic infections. Although azoles, such as itraconazole and voriconazole, and amphotericin B have significant activity against H. capsulatum, about 1 in 10 patients hospitalized due to histoplasmosis die. Hence, new approaches for managing disease are being sought. Over the past 10 years, studies have demonstrated that monoclonal antibodies (mAbs) can modify the pathogenesis of histoplasmosis. Disease has been shown to be impacted by mAbs targeting either fungal cell surface proteins or host co-stimulatory molecules. This review will detail our current knowledge regarding the impact of antibody therapy on histoplasmosis.

Detection of antibodies against Paracoccidioides brasiliensis melanin in in vitro and in vivo studies during infection.

Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice.

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.