Characterisation of a microelectrochemical biosensor for real-time detection of brain extracellular d-serine.

A modified development protocol and concomitant characterisation of a first generation biosensor for the detection of brain extracellular d-serine is reported. Functional parameters important for neurochemical monitoring, including sensor sensitivity, O2 interference, selectivity, shelf-life and biocompatibility were examined. Construction and development involved the enzyme d-amino acid oxidase (DAAO), utilising a dip-coating immobilisation method employing a new extended drying approach. The resultant Pt-based polymer enzyme composite sensor achieved high sensitivity to d-serine (0.76 ± 0.04 nA mm-2. µM-1) and a low µM limit of detection (0.33 ± 0.02 µM). The in-vitro response time was within the solution stirring time, suggesting potential sub-second in-vivo response characteristics. Oxygen interference studies demonstrated a 1 % reduction in current at 50 µM O2 when compared to atmospheric O2 levels (200 µM), indicating that the sensor can be used for reliable neurochemical monitoring of d-serine, free from changes in current associated with physiological O2 fluctuations. Potential interference signals generated by the principal electroactive analytes present in the brain were minimised by using a permselective layer of poly(o-phenylenediamine), and although several d-amino acids are possible substrates for DAAO, their physiologically relevant signals were small relative to that for d-serine. Additionally, changing both temperature and pH over possible in vivo ranges (34-40 °C and 7.2-7.6 respectively) resulted in no significant effect on performance. Finally, the biosensor was implanted in the striatum of freely moving rats and used to monitor physiological changes in d-serine over a two-week period.

A physiatrist's role in managing unique challenges in pregnancy and delivery in a patient with incomplete lumbar SCI: a case report.

INTRODUCTION: Women of childbearing age make up around 5-10% of individuals with spinal cord injury (SCI) and may face unique medical and functional complications during pregnancy, including prolonged hospitalization and increased risk of early rehospitalization due to falls. CASE PRESENTATION: Here, we discuss a case of a young ambulatory woman with a lumbar motor incomplete spinal cord injury who underwent successful delivery via cesarean section and the role of the physiatrist in the management of the patient's antepartum, intrapartum, and postpartum complications. The patient faced significant antepartum challenges secondary to her neurogenic bladder and pelvic floor weakness, resulting in increased use of her manual wheelchair. The physiatry team assisted with the co-development of a multidisciplinary bladder plan for increased urinary frequency and urinary tract infection prevention with the patient's obstetrics physician (OB). In addition, the physiatry team assisted with the procurement of a new wheelchair suited for the patient's pregnancy and childcare needs in anticipation of decreased mobility during this time. Regarding intrapartum challenges, the physiatry team worked with the patient and her OB to develop a safe birth plan considering the method of delivery, epidural usage, and the need for pelvic floor therapy before and after childbirth. DISCUSSION: The patient had a successful cesarean section delivery, with return to independent mobility soon after childbirth. In summary, this case demonstrates that there is a need for a multidisciplinary approach to patients with SCI during pregnancy and that the role of physiatry is critical to optimizing medical and functional outcomes.

The Impacts of Burn Severity and Frequency on Erosion in Western Arnhem Land, Australia.

Wildfires are pivotal to the functioning of many ecosystems globally, including the magnitude of surface erosion rates. This study aims to investigate the relationships between surface erosion rates and wildfire intensity in the tropical north savanna of Australia. The occurrence of fires in western Arnhem Land, Northern Territory, Australia was determined with remotely sensed digital datasets as well as analogue erosion measurement methods. Analysis was performed using satellite imagery to quantify burn severity via a monthly delta normalised burn ratio (dNBR). This was compared and correlated against on-ground erosion measurements (erosion pins) for 13 years. The dNBR for each year (up to +0.4) displayed no relationship with subsequent erosion (up to ±4 mm of erosion/deposition per year). Poor correlation was attributed to low fire severity, patchy burning, significant time between fires and erosion-inducing rainfall. Other influences included surface roughness from disturbances from feral pigs and cyclone impacts. The findings here oppose many other studies that have found that fires increase surface erosion. This accentuates the unique ecosystem characteristics and fire regime properties found in the tropical Northern Territory. Scenarios of late dry season fires with high severity were not observed in this study and require more investigations. Ecosystems such as the one examined here require specialised management practices acknowledging the specific ecosystem functions and processes. The methods employed here combine both analogue and digital sensors to improve understandings of a unique environmental system.

Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

Design optimisation and characterisation of an amperometric glutamate oxidase-based composite biosensor for neurotransmitter l-glutamic acid.

A polymer/enzyme composite biosensor for monitoring neurochemical glutamate was performance optimised in vitro for sensitivity, selectivity and stability. This first generation Pt/glutamate oxidase-based sensor displayed appropriate sensitivity (90.4 ± 2.0 nA cm-2 µM-1). It also has ideal stability/biocompatibility with no significant decrease in response observed for repeated calibrations, exposure to electron beam sterilisation, or following storage at 4 °C either dry (28 days) or in ex-vivo rodent brain tissue (14 days). Potential non-glutamate contributing signals, generated by extracellular levels of the principal endogenous electroactive interferents, were typically <5% of the basal (10 µM) glutamate response. Changes in molecular oxygen (the natural enzyme mediator) over the normal brain tissue range of 40-80 µM had minimal effect on the glutamate signal for concentrations of 10 and 100 µM (Mean KMO2 = 1.86 ± 0.74 µM, [O2]90% = ca. 15 µM). Additionally, a low µM calculated limit of detection (0.44 ± 0.05) and rapid response time (ca. 1.67 ± 0.06 s), combined with no effect of pH and temperature changes over physiologically relevant ranges (7.2-7.6 and 34-40 °C respectively), collectively suggest that this composite biosensor should reliably detect l-glutamate when used for neurochemical monitoring. Preliminary experiments involving implantation in the striatum of freely moving rats demonstrated stable recording over several weeks, and reliable detection of physiological changes in glutamate in response to behavioural/neuronal activation (locomotor activity and restraint stress).

Quantifying spatial non-stationarity in the relationship between landscape structure and the provision of ecosystem services: An example in the New Zealand hill country.

Knowing how landscape structure affects the provision of ecosystem services (ES) is an important first step toward better landscape planning. Because landscape structure is often heterogenous across space, modelling the relationship between landscape structure and the provision of ES must account for spatial non-stationarity. This paper examines the relationship between landscape structure and the provision of ES using a hill country and steep-land case farm in New Zealand. Indicators derived from land cover and topographical data such as Largest Patch Index (LPI), Contrast Class Edge (CCE), Edge Density (ED), and Terrain slope (SLOPE) were used to examine the landscape's structure and pattern. Measures of pasture productivity, soil erosion control, and water supply were derived with InVEST tools and spatial analysis in a GIS. Multiscale Geographically Weighted Regression (MGWR) was used to evaluate the relationship between indicators of landscape structure and the provisioning of ES. Other regression models, including Ordinary Least Square (OLS) and Geographically Weighted Regression (GWR), were carried out to evaluate the performance of MGWR. Results showed that landscape patterns significantly affect the supply of all mapped ES, and this varies across the landscape, dependent on the pattern of topographical features and land cover pattern and structure. MWGR outperformed other OLS and GWR in terms of explanatory power of the ES determinants and had a better ability to deal with the presence of spatial autocorrelation. Spatially and quantitatively detailed variations of the relationship between landscape structure and the provision of ES provide a scientific basis to inform the design of sustainable multifunctional landscapes. Information derived from this analysis can be used for spatial planning of farmed landscapes to promote multiple ES which meet multiple sustainable development objectives.

Development and validation of a real-time microelectrochemical sensor for clinical monitoring of tissue oxygenation/perfusion.

Oxygen is of critical importance to tissue viability and there is increasing demand for its reliable real-time clinical monitoring in order to prevent, diagnose, and treat several pathological disorders, including hypoxia, stroke and reperfusion injury. Herein we report the development and characterisation of a prototype clinical O2 sensor, and its validation in vivo, including proof-of-concept monitoring in patients undergoing surgery for carpal tunnel release. An integrated platinum-based microelectrochemical device was custom designed and controlled using a miniaturised telemetry-operated single channel clinical potentiostat. The in vitro performance of different sensor configurations is presented, with the best sensor design (S2) displaying appropriate linearity (R2 = 0.994) and sensitivity (0.569 ± 0.022 nA µM-1). Pre-clinical validation of S2 was performed in the hind limb muscle of anaesthetised rats; tourniquet application resulted in a significant rapid decrease in signal (90 ± 27%, [ΔO2] ca. 140 ± 18 µM), with a return to baseline within a period of ca. 3 min following tourniquet release. Similar trends were observed in the clinical study; an immediate decrease in signal (39 ± 3%, [ΔO2] ca. 30 ± 20 µM), with basal levels re-established within 2 min of tourniquet release. These results confirm that continuous real-time monitoring of dynamic changes in tissue O2 can serve as an indicator of reperfusion status in patients undergoing carpal tunnel surgery, and suggests the potential usefulness of the developed microelectrochemical sensor for other medical conditions where clinical monitoring of O2 and perfusion is important.

A first nation-wide assessment of soil-transmitted helminthiasis in Fijian primary schools, and factors associated with the infection, using a lymphatic filariasis transmission assessment survey as surveillance platform.

BACKGROUND: Soil-transmitted helminthiasis (STH) is endemic in Fiji but its prevalence is not known and likely to have changed after a decade of mass drug administration (MDA) for lymphatic filariasis (LF). By linking with LF transmission assessment surveys (LF-TAS), we undertook the first nation-wide assessment of STH in Fijian primary schools, as well as an analysis of factors associated with STH infections. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional assessment for STH was conducted in all four Divisions of Fiji from 2014 to 2015. In the Western, Central, and Northern Divisions, schools were sub-sampled after LF-TAS, while, in the Eastern Division, schools were selected via simple random sampling. For the diagnosis of STH, stool samples were examined by coproscopy with a single Kato-Katz thick smear (KK) and the formol-ether-acetate concentration technique, except for the samples from the Eastern Division where only KK was used. Mean prevalence of any STH among class 1-2 students at the national level was 10.5% (95% CI: 6.9-15.5). Across the three Divisions via LF-TAS, the prevalence levels for ascariasis were 8.7% (95% CI: 4.3-16.6), hookworm 3.9% (95% CI: 2.3-6.6) and trichuriasis 0%. In the Eastern Division, ascariasis prevalence was 13.3% (95% CI: 6.4-25.6), and hookworm 0.7% (95% CI: 0.2-2.5), with one case of trichuriasis. Among class 3-8 students, ascariasis prevalence was lower. Lower risk of any STH was associated with wearing shoes (adjusted OR 0.54, 95% CI: 0.32-0.90) and having piped water from the Fiji Water Authority at home (adjusted OR 0.48, 95% CI: 0.25-0.92). CONCLUSIONS: After a decade of community-based LF-MDA, STH in school-age children in Fiji is now close to 10%, but localities of endemicity remain. Preventive chemotherapy should be maintained in areas with elevated STH prevalence alongside targeted delivery of integrated WASH interventions. LF-TAS has provided an opportunity to develop future public health surveillance platforms.

Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium.

Systemic infection triggers a spectrum of metabolic and behavioral changes, collectively termed sickness behavior, which while adaptive, can affect mood and cognition. In vulnerable individuals, acute illness can also produce profound, maladaptive, cognitive dysfunction including delirium, but our understanding of delirium pathophysiology remains limited. Here, we used bacterial lipopolysaccharide (LPS) in female C57BL/6J mice and acute hip fracture in humans to address whether disrupted energy metabolism contributes to inflammation-induced behavioral and cognitive changes. LPS (250 µg/kg) induced hypoglycemia, which was mimicked by interleukin (IL)-1ß (25 µg/kg) but not prevented in IL-1RI-/- mice, nor by IL-1 receptor antagonist (IL-1RA; 10 mg/kg). LPS suppression of locomotor activity correlated with blood glucose concentrations, was mitigated by exogenous glucose (2 g/kg), and was exacerbated by 2-deoxyglucose (2-DG) glycolytic inhibition, despite preventing IL-1ß synthesis. Using the ME7 model of chronic neurodegeneration in female mice, to examine vulnerability of the diseased brain to acute stressors, we showed that LPS (100 µg/kg) produced acute cognitive dysfunction, selectively in those animals. These acute cognitive impairments were mimicked by insulin (11.5 IU/kg) and mitigated by glucose, demonstrating that acutely reduced glucose metabolism impairs cognition selectively in the vulnerable brain. To test whether these acute changes might predict altered carbohydrate metabolism during delirium, we assessed glycolytic metabolite levels in CSF in humans during inflammatory trauma-induced delirium. Hip fracture patients showed elevated CSF lactate and pyruvate during delirium, consistent with acutely altered brain energy metabolism. Collectively, the data suggest that disruption of energy metabolism drives behavioral and cognitive consequences of acute systemic inflammation.SIGNIFICANCE STATEMENT Acute systemic inflammation alters behavior and produces disproportionate effects, such as delirium, in vulnerable individuals. Delirium has serious short and long-term sequelae but mechanisms remain unclear. Here, we show that both LPS and interleukin (IL)-1ß trigger hypoglycemia, reduce CSF glucose, and suppress spontaneous activity. Exogenous glucose mitigates these outcomes. Equivalent hypoglycemia, induced by lipopolysaccharide (LPS) or insulin, was sufficient to trigger cognitive impairment selectively in animals with existing neurodegeneration and glucose also mitigated those impairments. Patient CSF from inflammatory trauma-induced delirium also shows altered brain carbohydrate metabolism. The data suggest that the degenerating brain is exquisitely sensitive to acute behavioral and cognitive consequences of disrupted energy metabolism. Thus "bioenergetic stress" drives systemic inflammation-induced dysfunction. Elucidating this may offer routes to mitigating delirium.

Environmental factors associated with diarrhoea prevalence among under-five children in the Mataniko settlements in Honiara, Solomon Islands.

INTRODUCTION: Children aged less than 5 years are often at high risk of diarrhoeal infection. In the Solomon Islands, diarrhoea is the second leading cause of under-five mortality with about one in every 10 children dying from it before reaching 5 years. This study aims to assess environmental factors that are associated with under-five diarrhoea prevalence in the Mataniko informal settlements, in Honiara, Solomon Islands. METHODS: Three out of the six settlements along the Mataniko River corridor were randomly selected. Caregivers who were taking care of at least one child under 5 years, and had signed a voluntary informed consent form, were included in the study. Instruments employed to collect the study variables were global positioning system technology and a questionnaire. Each child's medical record was used to verify the date of his or her diarrhoeal status. The data were entered and analysed using SPSS (v23). Binary logistic regression was used to measure the strength of association between under-five diarrhoea and the independent variables. A p-value of <0.05 was considered as statistically significant (p<0.05). RESULTS: A total of 205 caregivers with at least one child under 5 years participated in the study. Approximately half (45.9%) of the participants reported that their children (<5 years) had suffered with at least one episode of diarrhoea within the 2 weeks prior to the survey. Of the participants, 73.2% did not own a toilet facility and 61.0% of households were built on low-altitude areas (≤19 m above sea level), and above half (70.6%) were built near (≤125 m) the river. The presence of stagnant wastewater, flies, solid waste and water-filled containers near households, plus the distance of under-five households from the river, were found to be directly associated with under-five diarrhoea in the Mataniko informal settlements (p<0.05). CONCLUSION: Awareness and advocacy programs on environmental hygiene, food hygiene and potential health risks about the river should be ongoing at the community level.

The Use of the Abdominal Aortic and Junctional Tourniquet Versus Combat Gauze in a Porcine Hemicorporectomy Model.

BACKGROUND: Junctional hemorrhage is a potentially preventable cause of death. The Abdominal Aortic and Junctional Tourniquet (AAJT) compresses major vascular structures and arrests blood flow in exsanguinating hemorrhage. In a human model, the AAJT was effective in stopping blood flow in the femoral arteries via compression of the distal aorta. This study compares the ability of AAJT and Combat Gauze (CG) to stop hemorrhagic bleeding from a hemicorporectomy in a swine model. METHOD: Six anesthetized swine were used. Carotid arterial catheters were placed for continuous mean arterial pressure (MAP) readings. A hemicorporectomy was accomplished with a blade lever device by cutting the animal through both femoral heads transecting the proximal iliac arteries and veins. Hemorrhage control was attempted with the AAJT and regular Kerlix gauze or CG packing and direct pressure followed by Kerlix gauze placed over the CG. The primary outcome measure was survival at 60 minutes. RESULTS: The 60-minute survival was 100% for the AAJT and 0% for the CG group. During the 60-minute monitoring period, only one CG animal achieved hemostasis. For the AAJT group, the mean time to hemostasis was 30 seconds. Initial MAP was higher in the AAJT group (mean, 87mmHg) than the CG group (mean, 70mmHg). The mean 60-minute MAP was 73mmHg for the AAJT group. Mean blood loss at 5 minutes and mean total blood loss were greater in the CG group than in the AAJT group. CONCLUSION: AAJT is superior to CG in controlling hemorrhage in a junctional wound in a swine model.

Cardiovascular Disease Risk Factors and Physical Fitness in Volunteer Firefighters.

Forty-seven percent of volunteer firefighter line of duty deaths are caused by cardiovascular events. Aggressive cardiovascular disease (CVD) risk factor reduction and improved physical fitness could reduce CVD mortality within this population. We assessed CVD risk factors and physical fitness in a large cohort of volunteer firefighters to help establish a health and fitness profile of this population, which may serve as evidence for the need to initiate programs aimed at reducing morbidity and mortality caused by CVD in the volunteer fire service. Seventy-four male volunteer firefighters were assessed for eight CVD risk factors and anthropometric characteristics. Physical fitness was assessed via push-ups, sit-ups, and the YMCA step test. Sixty-eight percent of the firefighters had two or more CVD risk factors. The sample was considered obese via body fat percentage (25.3 ± 5.7%), 27% were hypertensive, 30% had hypercholesterolemia, and 46% were sedentary. The average number of sit-ups performed was 27.3 ± 10.5, which was ranked in the 25th percentile. The average heart rate after the YMCA step test was 160.2 ± 14.6 bpm, which was ranked very poor. The number of CVD risk factors and poor physical fitness in this cohort of volunteer firefighters was noteworthy. Most volunteer firefighters in our sample were at elevated risk for CVD and had inadequate physical fitness. This evidence conveys the need to initiate physical activity and nutrition outreach programs, led by health and fitness professionals, aimed at reducing firefighter morbidity and mortality within the volunteer fire service.

Predictive risk mapping of an environmentally-driven infectious disease using spatial Bayesian networks: A case study of leptospirosis in Fiji.

INTRODUCTION: Leptospirosis is a zoonotic disease responsible for over 1 million severe cases and 60,000 deaths annually. The wide range of animal hosts and complex environmental drivers of transmission make targeted interventions challenging, particularly when restricted to regression-based analyses which have limited ability to deal with complexity. In Fiji, important environmental and socio-demographic factors include living in rural areas, poverty, and livestock exposure. This study aims to examine drivers of transmission under different scenarios of environmental and livestock exposures. METHODS: Spatial Bayesian networks (SBN) were used to analyse the influence of livestock and poverty on the risk of leptospirosis infection in urban compared to rural areas. The SBN models used a combination of spatially-explicit field data from previous work and publically available census information. Predictive risk maps were produced for overall risk, and for scenarios related to poverty, livestock, and urban/rural setting. RESULTS: While high, rather than low, commercial dairy farm density similarly increased the risk of infection in both urban (12% to 18%) and rural areas (70% to 79%), the presence of pigs in a village had different impact in rural (43% to 84%) compared with urban areas (4% to 24%). Areas with high poverty rates were predicted to have 26.6% and 18.0% higher probability of above average seroprevalence in rural and urban areas, respectively. In urban areas, this represents >300% difference between areas of low and high poverty, compared to 43% difference in rural areas. CONCLUSIONS: Our study demonstrates the use of SBN to provide valuable insights into the drivers of leptospirosis transmission under complex scenarios. By estimating the risk of leptospirosis infection under different scenarios, such as urban versus rural areas, these subgroups or areas can be targeted with more precise interventions that focus on the most relevant key drivers of infection.

Multicomponent analysis using a confocal Raman microscope.

Measuring the concentration of multiple chemical components in a low-volume aqueous mixture by Raman spectroscopy has received significant interest in the literature. All of the contributions to date focus on the design of optical systems that facilitate the recording of spectra with high signal-to-noise ratio by collecting as many Raman scattered photons as possible. In this study, the confocal Raman microscope setup is investigated for multicomponent analysis. Partial least-squares regression is used to quantify physiologically relevant aqueous mixtures of glucose, lactic acid, and urea. The predicted error is 17.81 mg/dL for glucose, 10.6 mg/dL for lactic acid, and 7.6 mg/dL for urea, although this can be improved with increased acquisition times. A theoretical analysis of the method is proposed, which relates the numerical aperture and the magnification of the microscope objective, as well as the confocal pinhole size, to the performance of the technique.

Use of geographically weighted logistic regression to quantify spatial variation in the environmental and sociodemographic drivers of leptospirosis in Fiji: a modelling study.

BACKGROUND: Leptospirosis is a globally important zoonotic disease, with complex exposure pathways that depend on interactions between human beings, animals, and the environment. Major drivers of outbreaks include flooding, urbanisation, poverty, and agricultural intensification. The intensity of these drivers and their relative importance vary between geographical areas; however, non-spatial regression methods are incapable of capturing the spatial variations. This study aimed to explore the use of geographically weighted logistic regression (GWLR) to provide insights into the ecoepidemiology of human leptospirosis in Fiji. METHODS: We obtained field data from a cross-sectional community survey done in 2013 in the three main islands of Fiji. A blood sample obtained from each participant (aged 1-90 years) was tested for anti-Leptospira antibodies and household locations were recorded using GPS receivers. We used GWLR to quantify the spatial variation in the relative importance of five environmental and sociodemographic covariates (cattle density, distance to river, poverty rate, residential setting [urban or rural], and maximum rainfall in the wettest month) on leptospirosis transmission in Fiji. We developed two models, one using GWLR and one with standard logistic regression; for each model, the dependent variable was the presence or absence of anti-Leptospira antibodies. GWLR results were compared with results obtained with standard logistic regression, and used to produce a predictive risk map and maps showing the spatial variation in odds ratios (OR) for each covariate. FINDINGS: The dataset contained location information for 2046 participants from 1922 households representing 81 communities. The Aikaike information criterion value of the GWLR model was 1935·2 compared with 1254·2 for the standard logistic regression model, indicating that the GWLR model was more efficient. Both models produced similar OR for the covariates, but GWLR also detected spatial variation in the effect of each covariate. Maximum rainfall had the least variation across space (median OR 1·30, IQR 1·27-1·35), and distance to river varied the most (1·45, 1·35-2·05). The predictive risk map indicated that the highest risk was in the interior of Viti Levu, and the agricultural region and southern end of Vanua Levu. INTERPRETATION: GWLR provided a valuable method for modelling spatial heterogeneity of covariates for leptospirosis infection and their relative importance over space. Results of GWLR could be used to inform more place-specific interventions, particularly for diseases with strong environmental or sociodemographic drivers of transmission. FUNDING: WHO, Australian National Health & Medical Research Council, University of Queensland, UK Medical Research Council, Chadwick Trust.

Island-Wide Surveillance of Gastrointestinal Protozoan Infection on Fiji by Expanding Lymphatic Filariasis Transmission Assessment Surveys as an Access Platform.

As part of lymphatic filariasis (LF) transmission assessment surveys (TAS) on Fiji, an island-wide assessment of gastrointestinal protozoan infection was performed by inspection of a concomitant stool sample collection to investigate the distribution of parasitic protozoa. All grade 1 and 2 students of 69 schools on the two main islands were targeted in two phases (one in the Western Division and the other in the Central and Northern Divisions, except Taveuni sub-Division of Northern), where fecal samples of 1,800 students were available for coproscopy using formalin-ether-acetate concentration. The overall prevalence of Giardia infection was 1.6%, having 2.2% in Western and 0.8% in Central/Northern Divisions (P = 0.094). The school-level prevalence of giardiasis ranged from 0% to 15.4%, and hotspot analysis using the Getis-Ord Gi* method detected spatial heterogeneity of giardiasis prevalence in schools around Lautoka (Z-score = 3.36, P value < 0.05), an area affected by Cyclone Kofi in February 2014. Any protozoan infection prevalence was 4.9% in Western and 4.4% in Central/Northern Divisions (P = 0.825). Real-time polymerase chain reaction analysis to confirm the findings from a parasitological examination of a 10% stool archive in 95% ethanol from Western Division revealed an elevated prevalence of giardiasis up to 22.4%, the presence of Entamoeba histolytica, and the absence of Cryptosporidium parvum. Obtaining stool samples alongside LF TAS is a convenient access platform for cosurveillance of gastrointestinal protozoan infection and has pinpointed hitherto unknown hotspots of giardiasis in urban city centers of Fiji. This calls for greater attention to apply tailored water, sanitation and hygiene measures for the control of these parasites.

Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji.

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.

A cross-sectional seroepidemiological survey of typhoid fever in Fiji.

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks.

Real-time changes in hippocampal energy demands during a spatial working memory task.

Activity-dependent changes in hippocampal energy consumption have largely been determined using microdialysis. However, real-time recordings of brain energy consumption can be more accurately achieved using amperometric sensors, allowing for sensitive real-time monitoring of concentration changes. Here, we test the theory that systemic pre-treatment with glucose in rats prevents activity-dependent decreases in hippocampal glucose levels and thus enhances their performance in a spontaneous alternation task. Male Sprague Dawley rats were implanted into the hippocampus with either: 1) microdialysis probe; or 2) an oxygen sensor and glucose biosensor co-implanted together. Animals were pre-treated with either saline or glucose (250mg/kg) 30min prior to performing a single 20-min spontaneous alternation task in a +-maze. There were no significant differences found between either treatment group in terms of spontaneous alternation performance. Additionally, there was a significant difference found between treatment groups on hippocampal glucose levels measured using microdialysis (a decrease associated with glucose pre-treatment in control animals) but not amperometry. There were significant increases in hippocampal oxygen during +-maze exploration. Combining the findings from both methods, it appears that hippocampal activity in the spontaneous alternation task does not cause an increase in glucose consumption, despite an increase in regional cerebral blood flow (using oxygen supply as an index of blood flow) and, as such, pre-treatment with glucose does not enhance spontaneous alternation performance.

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance.