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.

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.

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.

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.

We investigate the 3-D matter distribution at $z\sim 2$ with high resolution ($R\sim 40,000$) spectra of QSO pairs and groups obtained with the UVES spectrograph at ESO VLT. Our sample is unique for the number density of objects and the variety of separations, between $\sim 0.5$ and 7 proper Mpc. We compute the real space cross-correlation function of the Lyman-$\alpha$ forest transmitted fluxes. There is a significant clustering signal up to $\sim 2$ proper Mpc, which is still present when absorption lines with high column density ($\log N \ge 13.8$) are excluded.

Floor type is one of the main features influencing the welfare of sows and piglets in farrowing crates. Yet it is difficult to reconcile the needs of the sow and her piglets through the use of one floor (Furniss et al., 1986). Hence the aim of this study was to identify a floor combination that optimises the welfare of the piglets in the farrowing crate.

The “aging” characteristics of an acetic acid/methanol solvent-based lead zirconate titanate (PZT) precursor solution, prepared by the Inverted Mixing Order (IMO) process, have been studied for an extended period of time. The changes in film properties were characterized using optical microscopy, optical scattering, and ferroelectric testing. Films generated from the IMO process exhibit an increase in thickness as a function of solution age due to chemical “aging” (esterification) of the precursor solution. This increased thickness results in a decrease in the microstructural uniformity, which affects the electrical and optical properties. In order to understand and eventually control this phenomenon, we have quantified the “aging” of this solution using a variety of analytical methods, including 1H NMR spectroscopy, pH measurements, and Fourier transform infrared (FTIR) spectroscopy. It is of note that we have discovered a method that circumvents this “aging” problem by removal of the volatile material, forming an IMO powder which can be redissolved to produce high quality PZT thin films whenever desired.

A nonaqueous coprecipitation process has been developed to prepare controlled stoichiometry lithium manganese oxalate precipitates. The process involved mixing a methanolic Li-Mn nitrate solution with a methanolic solution containing tetramethylammonium oxalate as the precipitating agent. The resulting oxalates were readily converted to a variety of phase pure lithium manganese oxides at moderate temperatures (≤600°C), where the phase formed was determined by the initial Li/Mn ratio in the starting solution. Metal cation dopants have been incorporated into the oxalate precipitate by dissolving the appropriate metal nitrate in the Li-Mn precursor solution The various starting solutions, oxalate precipitates, and calcined oxides have been extensively characterized using a variety of techniques, including 7Li NMR, TGA/DTA, SEM, and XRD. Results indicate that a strong interaction occurs between Li and Mn in the nitrate solution which carries over into the oxalate phase during precipitation. The morphology and the crystallite size of the oxide powders were shown to be controlled by the morphology of the oxalate precursor and the oxalate calcination temperature, respectively. The results of initial cathode performance tests with respect to dopant type (Al, Ni, Co) and concentration for LiMn2O4 are also reported.