Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies.

How do local differences in saltmarsh ecology influence disease vector mosquito populations?

Saltmarsh breeding mosquitoes are an important source of vectors for arboviral transmission. In southern Australia, the most prominent vector borne disease, Ross River virus (Togaviridae: Alphavirus) (RRV), is transmitted by the saltmarsh mosquito (Diptera: Culicidae) Aedes camptorhynchus (Thomson). However, the factors driving the abundance of this mosquito within and among saltmarshes are poorly understood. To predict the abundance of this mosquito within saltmarshes, the environmental conditions and aquatic invertebrate ecology of three temperate saltmarshes habitats were monitored over two seasons. Up to 44% of first-instar mosquito numbers and 21% of pupal numbers were accounted for by environmental variables. Samphire vegetation cover was a common predictor of first-instar numbers across sites although, between saltmarshes, aquatic factors such as high salinity, temperatures less than 22 °C and water body volume were important predictors. The identified predictors of pupal numbers were more variable and included high tides, waterbody volume and alkalinity. The composition of invertebrate functional feeding groups differed between saltmarshes and showed that an increased diversity led to fewer mosquitoes. It was evident that apparently similar saltmarshes can vary markedly in invertebrate assemblages, water availability and conditions through tidal inundations, rainfall or waterbody permanency. The present study advances insight into predictors of vector mosquito numbers that drive the risk of RRV outbreaks.

Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord Injury, Implicating Novel Mechanisms of Pathogenesis.

L-selectin, a lectin-like receptor on all leukocyte classes, functions in adhesive and signaling roles in the recruitment of myeloid cells from the blood to sites of inflammation. Here, we consider L-selectin as a determinant of neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord-injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery with greater white matter sparing relative to wild-type (WT) mice and reduced oxidative stress in the injured cord at 72 h post-SCI. There was a partial and transient reduction in accumulation of neutrophils in the injured spinal cords of KOs at 24 h post-injury. To complement these findings with KO mice, we sought a pharmacologic means for lowering L-selectin levels. We found that diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin from the cell surface of myeloid subsets, specifically neutrophils and non-classical monocytes, in the blood and the injured spinal cord. Diclofenac administration to injured WT mice enhanced neurological recovery to a level comparable to that of KOs but did not improve recovery in KOs. While diclofenac treatment had no effect on myeloid cell accumulation, there was a reduction in oxidative stress at 72 h post-SCI. These findings implicate L-selectin in secondary pathogenesis beyond a role in leukocyte recruitment and raise the possibility of repurposing diclofenac for the treatment of SCI.

Association between malaria incidence and meteorological factors: a multi-location study in China, 2005-2012.

This study aims to investigate the climate-malaria associations in nine cities selected from malaria high-risk areas in China. Daily reports of malaria cases in Anhui, Henan, and Yunnan Provinces for 2005-2012 were obtained from the Chinese Center for Disease Control and Prevention. Generalized estimating equation models were used to quantify the city-specific climate-malaria associations. Multivariate random-effects meta-regression analyses were used to pool the city-specific effects. An inverted-U-shaped curve relationship was observed between temperatures, average relative humidity, and malaria. A 1 °C increase of maximum temperature (T max) resulted in 6·7% (95% CI 4·6-8·8%) to 15·8% (95% CI 14·1-17·4%) increase of malaria, with corresponding lags ranging from 7 to 45 days. For minimum temperature (T min), the effect estimates peaked at lag 0 to 40 days, ranging from 5·3% (95% CI 4·4-6·2%) to 17·9% (95% CI 15·6-20·1%). Malaria is more sensitive to T min in cool climates and T max in warm climates. The duration of lag effect in a cool climate zone is longer than that in a warm climate zone. Lagged effects did not vanish after an epidemic season but waned gradually in the following 2-3 warm seasons. A warming climate may potentially increase the risk of malaria resurgence in China.

Experts' Perceptions on China's Capacity to Manage Emerging and Re-emerging Zoonotic Diseases in an Era of Climate Change.

Zoonotic diseases transmitted by arthropods and rodents are a major public health concern in China. However, interventions in recent decades have helped lower the incidence of several diseases despite the country's large, frequently mobile population and socio-economic challenges. Increasing globalization, rapid urbanization and a warming climate now add to the complexity of disease control and prevention and could challenge China's capacity to respond to threats of emerging and re-emerging zoonoses. To investigate this notion, face-to-face interviews were conducted with 30 infectious disease experts in four cities in China. The case study diseases under discussion were malaria, dengue fever and haemorrhagic fever with renal syndrome, all of which may be influenced by changing meteorological conditions. Data were analysed using standard qualitative techniques. The study participants viewed the current disease prevention and control system favourably and were optimistic about China's capacity to manage climate-sensitive diseases in the future. Several recommendations emerged from the data including the need to improve health literacy in the population regarding the transmission of infectious diseases and raising awareness of the health impacts of climate change amongst policymakers and health professionals. Participants thought that research capacity could be strengthened and human resources issues for front-line staff should be addressed. It was considered important that authorities are well prepared in advance for outbreaks such as dengue fever in populous subtropical areas, and a prompt and coordinated response is required when outbreaks occur. Furthermore, health professionals need to remain skilled in the identification of diseases for which incidence is declining, so that re-emerging or emerging trends can be rapidly identified. Recommendations such as these may be useful in formulating adaptation plans and capacity building for the future control and prevention of climate-sensitive zoonotic diseases in China and neighbouring countries.

Improving public health intervention for mosquito-borne disease: the value of geovisualization using source of infection and LandScan data.

Epidemiological studies use georeferenced health data to identify disease clusters but the accuracy of this georeferencing is obfuscated by incorrectly assigning the source of infection and by aggregating case data to larger geographical areas. Often, place of residence (residence) is used as a proxy for the source of infection (source) which may not be accurate. Using a 21-year dataset from South Australia of human infections with the mosquito-borne Ross River virus, we found that 37% of cases were believed to have been acquired away from home. We constructed two risk maps using age-standardized morbidity ratios (SMRs) calculated using residence and patient-reported source. Both maps confirm significant inter-suburb variation in SMRs. Areas frequently named as the source (but not residence) and the highest-risk suburbs both tend to be tourist locations with vector mosquito habitat, and camping or outdoor recreational opportunities. We suggest the highest-risk suburbs as places to focus on for disease control measures. We also use a novel application of ambient population data (LandScan) to improve the interpretation of these risk maps and propose how this approach can aid in implementing disease abatement measures on a smaller scale than for which disease data are available.

Seroprevalence of antibodies to Rickettsia typhi in the Waikato region of New Zealand.

The first reported New Zealand-acquired case of murine typhus occurred near Auckland in 1989. Since then, 72 locally acquired cases have been recorded from northern New Zealand. By 2008, on the basis of the timing and distribution of cases, it appeared that murine typhus was escalating and spreading southwards. To explore the presence of Rickettsia typhi in the Waikato region, we conducted a seroprevalence study, using indirect immunofluorescence, Western blot, and cross-adsorption assays of blood donor samples. Of 950 human sera from Waikato, 12 (1·3%) had R. typhi antibodies. The seroprevalence for R. typhi was slightly higher in northern Waikato (1·4%) compared to the south (1·2%; no significant difference, χ 2 P = 0·768 at P < 0·05). Our results extend the reported southern range of R. typhi by 140 km and indicate it is endemic in Waikato. Evidence of past Rickettsia felis infections was also detected in six sera. Globally, R. felis is an emerging disease of concern and this pathogen should also be considered when locally acquired rickettsiosis is suspected. If public health interventions are to be implemented to reduce the risk of rickettsioses as a significant public health problem, improvements in rickettsial diagnostics and surveillance will be necessary.

Diffusivity measurements differentiate benign from malignant lesions in patients with peripheral neuropathy or plexopathy.

BACKGROUND AND PURPOSE: Peripheral nerve disorders caused by benign and malignant primary nerve sheath tumors, infiltration or compression of nerves by metastatic disease, and postradiation neuritis demonstrate overlapping features on conventional MR imaging but require vastly different therapeutic approaches. We characterize and compare diffusivities of peripheral nerve lesions in patients undergoing MR neurography for peripheral neuropathy or brachial or lumbosacral plexopathy. MATERIALS AND METHODS: Twenty-three patients, referred for MR neurography at our institution between 2003 and 2009 for a peripheral mononeuropathy or brachial or lumbosacral plexopathy and whose examinations included DWI, received a definitive diagnosis, based on biopsy results or clinical and imaging follow-up, for a masslike or infiltrative peripheral nerve or plexus lesion suspicious for tumor. Mean ADC values were determined within each lesion and compared across 3 groups (benign lesions, malignant lesions, and postradiation changes). RESULTS: Both ANOVA and Kruskal-Wallis tests demonstrated a statistically significant difference in ADC values across the 3 groups (P = .000023, P = .00056, respectively). Post hoc pair-wise comparisons showed that the ADC within malignant tumors differed significantly from that within benign tumors and postradiation changes. ADC within benign tumors and postradiation changes did not differ significantly from each other. CONCLUSIONS: DWI may be highly effective for the differentiation of benign from malignant peripheral nerve masslike or infiltrative lesions.

Is restoring an ecosystem good for your health?

It is well known that the degradation of ecosystems can have serious impacts on human health. There is currently a knowledge gap on what impact restoring ecosystems has on human health. In restoring ecosystems there is a drive to restore the functionality of ecosystems rather than restoring ecosystems to 'pristine' condition. Even so, the complete restoration of all ecosystem functions is not necessarily possible. Given the uncertain trajectory of the ecosystem during the ecosystem restoration process the impact of the restoration on human health is also uncertain. Even with this uncertainty, the restoration of ecosystems for human health is still a necessity.

Utilisation of beds on the general medical unit by 'non-acute medical' patients: a retrospective study of incidence and cost in two Tasmanian regional medical hospital units.

BACKGROUND: Demand for healthcare services threatens to overwhelm the Australian healthcare system. Public hospitals have the largest component of expenditure growth and as such represent the largest opportunity for efficiency gains. Utilisation of inpatient hospital beds and in particular those on general medical units has not been studied in Australia. AIM: To undertake a retrospective patient medical record review of 200 sequential admissions to the medical wards in two regional Tasmanian hospitals to determine the incidence of non-acute medical patient admission to the medical unit, and the subsequent days in hospital that were not required for medical reasons. The cost of these days was estimated. RESULTS: Sixteen patient admissions (8%) could not be justified on medical grounds. Forty-eight (24%) patient admissions had at least one day hospital day that could not be justified on medical grounds. Of the 1438 total bed days, 475 (33%) were for non-medical reasons. The estimated cost of those non-medical bed days for this cohort was $764 800. CONCLUSIONS: The incidence of non-acute medical admissions and non-acute medical bed days to the medical unit and associated cost was significant. Further research is needed to design alternative care provision for such patients particularly in regional Australia. The potential savings to the Australian healthcare system could be significant.

Implementation partnerships in a community-based intergenerational oral health study.

BACKGROUND: University-community partnerships are a common strategy used in implementing community-based health promotion trials, yet few published studies report these interactions in detail. "Baby Smiles" was a five-year intervention study in Oregon, USA. The study involved 400 low-income women during and after pregnancy across four rural counties. In this report, we describe and assess four university-community health partnerships formed to support the intervention. METHODS: A community health partnership advisory group for the study was established in each of the four participating counties. Group membership ranged from 9 to 23 individuals. A survey was administered to the groups five times in a 2.5 year period. The survey asked members' opinions of the intervention's goals, scientific basis and relevance to their organisation. Questions also asked about members' knowledge of oral health, beliefs about access to dental care for low-income pregnant women and children in their county and how their organisation functioned. RESULTS: There was strong overall support by each partnership group despite differences in the groups' structure, foci and turnover in membership during intervention period. Responses to specific survey items indicating misinformation or negative opinions about oral health care were used to address weaknesses in study implementation throughout the conduct of the study. CONCLUSION: Systematic monitoring of community support for a multi-year oral health intervention is feasible and can identify potential barriers to address while the study is underway.

Dengue surveillance by proxy: travellers as sentinels for outbreaks in the Pacific Islands.

Sensitive surveillance systems are crucial for effective control of infectious disease outbreaks, and regional surveillance could provide valuable data to supplement global systems, improve sensitivity and timeliness of reporting, or capture otherwise undetected outbreaks. In New Zealand (NZ), there are no endemic arboviral diseases in humans, and the majority of dengue cases are imported from neighbouring Pacific Islands where comprehensive surveillance systems are under development. From 1997 to 2009, 679 cases of dengue were reported in NZ (74·2% acquired from the Pacific Islands), and the patterns of reported incidence of dengue acquired from different islands closely reflected local reported incidence in those areas. NZ is therefore in a unique position to provide early alerts on dengue outbreaks in the Pacific Islands. Such a strategy would reduce disease burden in both the Pacific Islands and NZ, and provide a model for transnational collaboration in disease surveillance with regional as well as global benefits.

Sunshine, rainfall, humidity and child pneumonia in the tropics: time-series analyses.

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51-0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8-14 days earlier was 0·95 (95% CI 0·91-1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Environmental drivers of Ross River virus in southeastern Tasmania, Australia: towards strengthening public health interventions.

In Australia, Ross River virus (RRV) is predominantly identified and managed through passive health surveillance. Here, the proactive use of environmental datasets to improve community-scale public health interventions in southeastern Tasmania is explored. Known environmental drivers (temperature, rainfall, tide) of the RRV vector Aedes camptorhynchus are analysed against cumulative case records for five adjacent local government areas (LGAs) from 1993 to 2009. Allowing for a 0- to 3-month lag period, temperature was the most significant driver of RRV cases at 1-month lag, contributing to a 23·2% increase in cases above the long-term case average. The potential for RRV to become an emerging public health issue in Tasmania due to projected climate changes is discussed. Moreover, practical outputs from this research are proposed including the development of an early warning system for local councils to implement preventative measures, such as public outreach and mosquito spray programmes.

Microbial risk classifications for recreational waters and applications to the Swan and Canning Rivers in Western Australia.

Protecting recreational water quality where 'whole-of-body contact' activities occur is important from a public health and economic perspective. Numerous studies have demonstrated that infectious illnesses occur when swimming in faecally polluted waters. With the release of the 2008 Australian recreational water guidelines, the Western Australian (WA) Department of Health conducted a formal evaluation to highlight the advantages of applying the microbial risk management framework to 27 swimming beaches in the Swan and Canning Rivers in Perth, WA. This involved a two-phase approach: (i) calculation of 95th percentiles using historical enterococci data; and (ii) undertaking sanitary inspections. The outcomes were combined to assign provisional risk classifications for each site. The classifications are used to promote informed choices as a risk management strategy. The study indicates that the majority of swimming beaches in the Swan-Canning Rivers are classified as 'very good' to 'good' and are considered safe for swimming. The remaining sites were classified as 'poor', which is likely to be attributed to environmental influences. Information from the study was communicated to the public via a series of press releases and the Healthy Swimming website. The guidelines provide a sound approach to managing recreational water quality issues, but some limitations were identified.

Recruiting rural dentally-avoidant adolescents into an intervention study.

AIM: To carry out a study designed to test an intervention to increase dental attendance in rural dentally-avoidant adolescents, to identify and recruit eligible adolescents. STUDY DESIGN AND METHODS: This study used a cross-sectional design to identify eligible adolescents. A total of 2,762 adolescents (60% of the enrolled students) from junior high and senior high schools in a rural county in Washington State (USA) were given a dental examination with a light and mirror by calibrated dental examiners using WHO criteria. Parents of children with serious dental needs were urged to seek dental care for their adolescent children. They were offered the chance to enroll their child in a study comparing two programs designed to help the adolescent decide whether to seek out dental care. A second group of emancipated adolescents and young adults (aged < 26 years) receiving services at the local college and health department was also screened, and eligible individuals were also offered the chance to enroll. RESULTS AND STATISTICS: Only 23 (6%) of 357 eligible junior and senior high school adolescents enrolled, compared with 24 (67%) of the 36 eligible emancipated adolescents and young adults. A second follow-up letter was sent to the 85 parents of un-enrolled adolescents with the most severe caries, offering direct assistance in obtaining dental care for their children; only 3 families responded. CONCLUSIONS: This study illustrates the difficulty in engaging adolescents in their oral health and utilization of oral health interventions. The results also suggest that slightly older rural individuals are more interested in and/or able to overcome barriers to seeking out dental care. Alternative strategies are suggested for recruiting avoidant adolescents.

Randomized equivalence trial of intensive and semiannual applications of fluoride varnish in the primary dentition.

For children in the primary dentition with high caries prevalence the standard semiannual application of fluoride varnish may not be successful in preventing tooth decay. Oftentimes this population is mobile and does not receive consistent preventive care. This trial tested whether an intensive fluoride 5% sodium varnish regimen (three applications/2 weeks) applied annually has an equivalent effect on caries progression in the primary dentition compared to single applications applied semiannually. This study was a randomized clinical trial with two treatment groups. All participants (n = 600; mean age +/- SD = 55.3 +/- 4.6 months) received three varnish applications (active varnish or placebo) at semiannual visits over 3 years. Once per year the intensive-treatment group received one set of three active treatments and three placebo treatments 6 months later, each time within 2 weeks. The standard group received one active and two placebo treatments every 6 months. Children were assessed clinically at baseline and 12, 24 and 36 months after the initiation of the study. The mean (SD) numbers of newly decayed primary tooth surfaces observed over 3 years were 9.8 (8.6) and 7.4 (7.7) in the intensive and standard groups, respectively. The adjusted rate ratio was 1.13 (95% CI = 0.94-1.37, p = 0.20). In conclusion, the trial failed to demonstrate clear evidence of a difference in efficacy. However, differences of up to 36% greater rates of caries in the intensive group could not be ruled out, thus equivalence of the treatments cannot be concluded.

Impact of dryland salinity on population dynamics of vector mosquitoes (Diptera: Culicidae) of Ross River virus in inland areas of southwestern Western Australia.

Clearing of native vegetation for agriculture since European settlement has left 1.047 million ha of southwestern Australia affected by a severe form of environmental degradation called dryland salinity, characterized by secondary soil salinization and waterlogging. This area may expand by a further 1.7-3.4 million ha if current trends continue. Detailed investigations of seasonal of adult and larval mosquito population dynamics were undertaken in the region to test the hypothesis that the development of dryland salinity and waterlogging in inland southwestern Australia has led to a succession of mosquito species and increased Ross River virus (family Togaviridae, genus Alphavirus, RRV) transmission risk. Aedes (Ochlerotatus) camptorhynchus (Thomson) made up >90% of adult mosquito collections in saline regions. Nonmetric multidimensional scaling and generalized estimating equations modeling demonstrated that it was strongly associated with increasing severity of dryland salinity. This article describes the first detailed investigation of the mosquito fauna of inland southwestern Australia, and it is the first description of the influence of secondary soil salinity on mosquito population dynamics. Despite the dominant presence of Ae. camptorhynchus, RRV disease incidence is not currently a significant population health priority in areas affected by dryland salinity. Potential limiting factors include local climatic impacts on the seasonal mosquito population dynamics, vertebrate host distribution and feeding behavior of Ae. camptorhynchus, and the scarce and uneven distribution of the human population in the region.