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Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
A search for Type Ia supernovae at cosmological distances is being undertaken in an attempt to exploit their standard candle property to constrain the mass density of the universe. We describe the rationale for such a program, the observational approach and strategy taken, and the progress made to date. The science that is being generated by the project in additional to supernova detection is also discussed briefly.
The environmental impact resulting from the use of fossil fuel as an energy source affects the entire globe. Eventually, fossil fuels will no longer be a reasonable source of energy and alternative energy sources will be needed. Thermoelectric materials (TE) that directly convert heat into electricity are a viable option to replace the conventional fossil fuel because they are reliable, cost effective, and use no moving parts. Recently researchers discovered the existence of giant Seebeck coefficient in manganese oxide (MnO2) powders, which ignited an increased interest in MnO2-based materials. In this work we present a systematic structural and electrical characterization of amorphous and crystalline MnxOy thin films. These films were deposited at room temperature on heated silicon and sapphire substrates by DC Magnetron Sputtering. Our preliminary results show that MnxOy/silicon thin films undergo a crystalline change from Mn2O3 to Mn3O4 as annealing temperature is increased from 300°C to 500°C.
Autoantibodies have been implicated in the etiologic pathway of depressive disorders. Here, we determine the association between the presence of a panel of autoantibodies at baseline and change in depression symptom score over 5-year follow-up in a cohort of healthy elderly Australians.
Serum samples from 2049 randomly selected subjects enrolled in the Hunter Community Study (HCS) aged 55–85 years were assayed for a range of autoimmune markers (anti-nuclear autoantibodies, extractable nuclear antigen autoantibodies, anti-neutrophil cytoplasmic autoantibodies, thyroid peroxidase autoantibodies, tissue transglutaminase autoantibodies, anti-cardiolipin autoantibodies, rheumatoid factor and cyclic citrullinated peptide autoantibodies) at baseline. Depression symptom score was assessed using the Centre for Epidemiological Study (CES-D) scale at baseline and 5 years later.
Autoantibody prevalence varied amongst our sample with ANA being the most prevalent; positive in 16% and borderline in 36% of study population. No evidence for a relationship was found between change in CES-D score over time and any autoimmune marker. Statins and high cholesterol were significantly associated with change in CES-D score over time in univariate analysis; however, these were probably confounded since they failed to remain significant following multivariable analysis.
Autoantibodies were not associated with change in CES-D score over time. These findings point to an absence of autoimmune mechanisms in the general population or in moderate cases of depression.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
On June 13, 2012, a group of key stakeholders, leaders, and national experts on tuberculosis (TB), occupational health, and laboratory science met in Atlanta, Georgia, to focus national discussion on the higher than expected positive results occurring among low-risk, unexposed healthcare workers undergoing serial testing with interferon-γ release assays (IGRAs). The objectives of the meeting were to present the latest clinical and operational research findings on the topic, to discuss evaluation and treatment algorithms that are emerging in the absence of national guidance, and to develop a consensus on the action steps needed to assist programs and physicians in the interpretation of serial testing IGRA results. This report summarizes its proceedings.
To assess whether a print-based intervention led to increased contact with consumer health organisations (CHOs) by general practice patients with chronic disease.
CHOs can enhance people's capacity to manage chronic illness by providing information, education and psychosocial support. However, these organisations appear to be grossly under-utilised by patients and clinicians.
A total of 276 patients completed a computer-assisted telephone interview before randomisation to an intervention (n = 141) or control (n = 135) group. The intervention consisted of mailed printed materials designed to encourage contact with a CHO relevant to the patient's main diagnosed chronic condition. Follow-up interviews were conducted 4 and 12 months later.
Patients with conditions other than diabetes who received the intervention were twice as likely as those in the control group to contact a consumer health organisation during the 12-month study period: 41% versus 21% (P < 0.001). No such effect was found for diabetes patients, probably because of pre-existing high levels of contact with diabetes organisations. The intervention package received strong patient endorsement. Low-intensity interventions may be effective in improving access to CHOs for patients with chronic disease.
Pasture-based Holstein–Friesian cows from three genetic groups differing in the Irish ‘Economic Breeding Index’ (EBI) value and genetic background, namely North-American (NA) national average EBI genetic merit (LOW-NA, n = 42), North-American high EBI genetic merit (HIGH-NA, n = 42) and New Zealand (NZ) high EBI genetic merit (HIGH-NZ, n = 42), were studied. These genetic groups have been selected in different environments: pasture for NZ and confinement for NA. The objective was to determine the effect of genetic group on haematological and acute phase proteins profiles (white blood cell (WBC) counts, red blood cell (RBC) counts, acute phase proteins: serum amyloid A (SAA) and haptoglobin), health (rectal temperature (RT), clinical mastitis (CM) and somatic cell score), calving performance (stillbirth, calving assistance) and post-partum reproductive parameters (endometritis and ovarian cyclicity). Blood sampling and data recording took place 3 weeks pre-calving up to 7 weeks post-calving. Linear mixed models, logistic regression and generalised estimating equations were used for data analysis. HIGH-NZ animals had the highest (P < 0.05) RBC mean corpuscular volume (50.0 fl), exhibited a different WBC distribution pattern (P < 0.05) and had the lowest (P < 0.05) mean RT (38.4°C) for the first 10 days post-calving. These findings suggest enhanced reticulocyte turnover, peripartum response mechanisms and thermoregulation in the HIGH-NZ compared to the other two genetic groups. LOW-NA animals had the highest SAA peak throughout the peripartum period (55.12 mg/l, P < 0.05) and a tendency for higher somatic cell scores (P < 0.10) in early lactation. The HIGH-NA animals had the lowest incidence of udder quarter milk sample bacteria at calving, suggesting better udder health when commencing lactation. No differences were detected between genetic groups in calving performance, post-partum reproductive parameters or CM in the first 42 days post-calving. These results suggest that while inherited peripartum adaptation strategies have been developed by the different genetic groups selected in different environments (pasture = NZ v. confinement = NA), such differences have minimal impact on peripartum clinical health.
The aim of the present study was to determine the effect of the genetic group of the Holstein–Friesian (HF) and pasture-based feeding system (3 × 2 factorial arrangement) on locomotion score (six gait aspects scored from one to five), clinical lameness and hoof disorders within a seasonal calving milk production system. The three genetic groups compared had an average Economic Breeding Index (EBI) value of 40, 70 and 80: representing the Irish national average genetic merit (LOW-NA), high EBI genetic merit of North American ancestry (HIGH-NA) and high EBI genetic merit of New Zealand ancestry (HIGH-NZ), respectively. Two feed systems were compared: a high grass allowance, low-concentrate system typical of spring-calving herds in Ireland (control) and a high-concentrate system. Data from 126 cows collected across a complete lactation period were analysed using generalised estimating equations and survival analysis. Genetic group of HF had a significant effect on locomotion score, clinical lameness and hoof disorders. Higher EBI cows (HIGH-NA and HIGH-NZ) had lower hazard of poor locomotion score in some gait aspects (e.g. spine curvature) and lower odds of clinical lameness in the first 200 days post-calving (Odds ratios 0.08 and 0.24, respectively, relative to the LOW-NA) and some hoof disorders (e.g. traumatic lesions) compared with LOW-NA cows. The high-concentrate feed system showed a higher incidence and severity of digital dermatitis (P < 0.01). Thus, high EBI cows have better locomotion, fewer cases of clinical lameness and less-severe hoof disorders (i.e. digital dermatitis, white line disease and traumatic lesions) than low EBI cows. These findings have important implications for cow welfare and productivity.
This study aimed to compare three woodchip out-wintering pad (OWP) designs, and indoor cubicle housing with regard to cow dirtiness scores during the winter housing period, and udder health during both the winter period and the following lactation, for spring-calving dairy cows. The treatments were: an uncovered (UP) and covered (CP) OWP with a concrete feed apron; an uncovered OWP with self-feed silage pit provided directly on the woodchips (SP); and indoor cubicle housing (IC). Data were compared during 2 years: year 1 was a case study while year 2 was an experimental study. In year 1, treatments were UP (space allowance = 12 m2/cow), CP (6 m2/cow) and IC. In year 2, all three OWP designs (12 m2/cow) were compared with IC. Animals were assigned to treatments at the end of lactation in the autumn, and remained there while dry until calving the following spring. Subsequently, all cows were at pasture during lactation. Outcome measures for analysis were cow dirtiness score, somatic cell score (SCS) and incidence of clinical mastitis during the dry period and during lactation. Quarter milk samples were also taken at drying off, calving and 3 weeks post partum both years, and at approximately 113 days in milk in year 2. Samples were analysed for presence of mastitis-causing agents and SCS was determined. Sub-clinical mastitis was diagnosed when cows had an SCS greater than 200 000, or California mastitis test greater than 1 in at least one quarter. In year 1, cows in CP were dirtier than cows in the other two treatments. These animals also had the highest SCS during lactation and tended to have more mastitis-causing agents isolated from quarter milk samples. In year 2, when all cows were stocked at the same density, cows in the sheltered OWP (i.e. CP) had similar dirtiness scores to cows in cubicles and significantly lower dirtiness scores than cows in the unsheltered OWP designs, i.e. UP and SP. However, there were no effects on SCS or quarter sample results. Cleaning of OWP’s stocked at 12 m2/cow reduced cow dirtiness scores. However, cleaning of CP in year 1 when cows were stocked at 6 m2/cow had no effect on dirtiness scores. We conclude that dry cows stocked at 12 m2/cow on OWP’s are unlikely to have udder health problems in the subsequent lactation. Furthermore, provision of shelter and cleaning of the woodchips are management factors that help to keep cows clean on OWP’s.