The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulu

Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvulus as an alternative to skin snips. We screened a plasma sample set of infected individuals followed up at four, 12 and 21 months after microfilaricidal (ivermectin, n = four), macrofilaricidal (doxycycline, n = nine), or combination treatment (n = five). Two parasite-derived miRNAs, cel-miR-71-5p and bma-lin-4, and O-150 repeat DNA were assessed. Highly abundant DNA repeat families identified in the O. volvulus genome were also evaluated. miRNAs were detected in two of 72 plasma samples (2.8%) and two of 47 samples (4.3%) with microfilaridermia using RT-qPCR. O-150 DNA was detected in eight (44.4%) baseline samples by qPCR and the number of positives declined post-treatment. One doxycycline-treated individual remained O-150 positive. However, only 11 (23.4%) samples with microfilaridermia were qPCR-positive. Analysis by qPCR showed novel DNA repeat families were comparatively less abundant than the O-150 repeat. Circulating parasite-derived nucleic acids are therefore insufficient as diagnostic tools or as biomarkers of treatment efficacy for O. volvulus

Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans

Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, ‘puppet-like’ ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). UBE3A is transcribed predominantly from the maternal allele in brain, but is expressed from both alleles in most other tissues. It has been proposed that brain-specific silencing of the paternal UBE3A allele is mediated by a large (>500 kb) paternal non-coding antisense transcript (UBE3A-ATS). There are several other examples of imprinting regulation involving antisense transcripts that share two main properties: (i) the sense transcript is repressed by antisense and (ii) the interaction between sense and antisense occurs in cis. We show here that, in a mouse model of AS, maternal transmission of Ube3a mutation leads to increased expression of the paternal Ube3a-ATS, suggesting that the antisense is modulated by sense rather than the reciprocal mode of regulation. Our observation that Ube3a regulates expression of Ube3a-ATS in trans is in contrast to the other cases of sense–antisense epigenetic cis-interactions and argues against a major role for Ube3a-ATS in the imprinting of Ube3a

The effect of head-to-head competition on behavioral thermoregulation, thermophysiological strain and performance during exercise in the heat

Background It has been suggested that pacing is a thermoregulatory behaviour. We investigated the effect of competition on pacing, performance and thermophysiological strain during exercise in the heat and the psychological factors mediating competition effects. Method Eighteen males (maximum oxygen uptake [VO2max] 3.69 [0.44] L min−1) undertook a preliminary 20-km cool (wet-bulb globe temperature [WBGT] 12 °C) cycling time trial (TT) and three experimental 20-km trials (balanced order): (i) cool TT (CoolSolo); (ii) hot (WBGT 26 °C) TT (HotSolo); (iii) hot head-to-head competition (HotH2H). During TTs, an avatar of the participant’s performance was visible. During HotH2H, participants believed they were competing against another participant, but the competitor’s avatar replicated their own preliminary (cool) TT.ResultsTTs (min:sec [SD]) slowed with increased ambient temperature [CoolSolo 35:31 (2:11) versus HotSolo 36:10 (2:26); p = 0.011]. This effect was negated by competition; performances were not different between HotH2H [35:17 (1:52)] and CoolSolo (p = 0.160) and were quicker in HotH2H versus HotSolo (p = 0.001). End-exercise rectal temperature, mean body temperature and physiological strain index were (p < 0.05) higher in HotH2H than either solo condition. Despite faster performance and greater thermophysiological strain, rating of perceived exertion (RPE), thermal comfort and sensation, and perceptual strain index were not different between HotH2H and HotSolo. The difference in end-exercise rectal temperature between HotH2H and HotSolo was related to pre-exercise anticipatory heart rate response (r = 0.608, p = 0.010) and participants’ propensity for deliberate risk-taking (B = 0.12, p < 0.001), whereas self-reported resilience predicted change in performance times between HotH2H versus HotSolo (B = − 9.40, p = 0.010). Conclusion Competition changes the relationship between perceived and actual thermophysiological state, altering behavioural thermoregulation and increasing thermophysiological strain; this could increase heat-illness risk. Psychophysiological and psychological measures may identify susceptible individuals

Changes in catastrophic health expenditure in post-conflict Sierra Leone: an Oaxaca-blinder decomposition analysis.

BACKGROUND: At the end of the eleven-year conflict in Sierra Leone, a wide range of policies were implemented to address both demand- and supply-side constraints within the healthcare system, which had collapsed during the conflict. This study examines the extent to which households' exposure to financial risks associated with seeking healthcare evolved in post-conflict Sierra Leone. METHOD: This study uses the 2003 and 2011 cross-sections of the Sierra Leone Integrated Household Survey to examine changes in catastrophic health expenditure between 2003 and 2011. An Oaxaca-Blinder decomposition approach is used to quantify the extent to which changes in catastrophic health expenditure are attributable to changes in the distribution of determinants (distributional effect) and to changes in the impact of these determinants on the probability of incurring catastrophic health expenditure (coefficient effect). RESULTS: The incidence of catastrophic health expenditure decreased significantly by 18% from approximately 50% in 2003 t0 32% in 2011. The decomposition analysis shows that this decrease represents net effects attributable to the distributional and coefficient effects of three determinants of catastrophic health expenditure - ill-health, the region in which households reside and the type of health facility used. A decrease in the incidence of ill-health and changes in the regional location of households contributed to a decrease in catastrophic health expenditure. The distributional effect of health facility types observed as an increase in the use of public health facilities, and a decrease in the use of services in facilities owned by non-governmental organizations (NGOs) also contributed to a decrease in the incidence of catastrophic health expenditure. However, the coefficient effect of public health facilities and NGO-owned facilities suggests that substantial exposure to financial risk remained for households utilizing both types of health facilities in 2011. CONCLUSION: The findings support the need to continue expanding current demand-side policies in Sierra Leone to reduce the financial risk of exposure to ill health

VAST: An ASKAP Survey for Variables and Slow Transients

The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae and orphan afterglows of gamma ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of five seconds and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.Comment: 29 pages, 8 figures. Submitted for publication in Pub. Astron. Soc. Australi

How do supply- and demand-side interventions influence equity in healthcare utilisation? Evidence from maternal healthcare in Senegal

The launch of the Millennium Development Goals in 2000, followed by the Sustainable Development Goals in 2015, and the increasing focus on achieving universal health coverage has led to numerous interventions on both supply- and demand-sides of health systems in low- and middle-income countries. While tremendous progress has been achieved, inequities in access to healthcare persist, leading to calls for a closer examination of the equity implications of these interventions. This paper examines the equity implications of two such interventions in the context of maternal healthcare in Senegal. The first intervention on the supply-side focuses on improving the availability of maternal health services while the second intervention, on the demand-side, abolished user fees for facility deliveries. Using three rounds of Demographic Health Surveys covering the period 1992 to 2010 and employing three measures of socioeconomic status (SES) based on household wealth, mothers' education and rural/urban residence – we find that although both interventions increase utilisation of maternal health services, the rich benefit more from the supply-side intervention, thereby increasing inequity, while the poor benefit more from the demand-side intervention i.e. reducing inequity. Both interventions positively influence facility deliveries in rural areas although the increase in facility deliveries after the demand-side intervention is more than the increase after the supply-side intervention. There is no significant difference in utilisation based on mothers’ education. Since people from different SES categories are likely to respond differently to interventions on the supply- and demand-side of the health system, policymakers involved in the design of health programmes should pay closer attention to concerns of inequity and elite capture that may unintentionally result from these interventions

Equity in the delivery of community healthcare to older people: findings from 10/66 Dementia Research Group cross-sectional surveys in Latin America, China, India and Nigeria

<p>Abstract</p> <p>Background</p> <p>To describe patterns of recent health service utilisation, and consequent out-of-pocket expenses among older people in countries with low and middle incomes, and to assess the equity with which services are accessed and delivered.</p> <p>Methods</p> <p>17,944 people aged 65 years and over were assessed in one-phase population-based cross-sectional surveys in geographically-defined catchment areas in nine countries - urban and rural sites in China, India, Mexico and Peru, urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and a rural site in Nigeria. The main outcome was use of community health care services in the past 3 months. Independent associations were estimated with indicators of need (dementia, depression, physical impairments), predisposing factors (age, sex, and education), and enabling factors (household assets, pension receipt and health insurance) using Poisson regression to generate prevalence ratios and fixed effects meta-analysis to combine them.</p> <p>Results</p> <p>The proportion using healthcare services varied from 6% to 82% among sites. Number of physical impairments (pooled prevalence ratio 1.37, 95% CI 1.26-1.49) and ICD-10 depressive episode (pooled PR 1.21, 95% CI 1.07-1.38) were associated with service use, but dementia was inversely associated (pooled PR 0.93, 95% CI 0.90-0.97). Other correlates were female sex, higher education, more household assets, receiving a pension, and health insurance. Standardisation for age, sex, physical impairments, depression and dementia did not explain variation in service use. There was a strong borderline significant ecological correlation between the proportion of consultations requiring out-of-pocket costs and the prevalence of health service use (r = -0.50, p = 0.09).</p> <p>Conclusions</p> <p>While there was little evidence of ageism, inequity was apparent in the independent enabling effects of education and health insurance cover, the latter particularly in sites where out-of-pocket expenses were common, and private health insurance an important component of healthcare financing. Variation in service use among sites was most plausibly accounted for by stark differences in the extent of out-of-pocket expenses, and the ability of older people and their families to afford them. Health systems that finance medical services through out-of-pocket payments risk excluding the poorest older people, those without a secure regular income, and the uninsured.</p