Effect of vaccination against gonadotrophin-releasing hormone, using Improvac®, on growth performance, body composition, behaviour and acute phase proteins

The objective of this study was to evaluate the effect of vaccination against GnRH on performance traits, pig behaviour and acute phase proteins. A total of 120 pigs (36 non-castrated males, NCM; 36 males to be vaccinated, IM; 24 castratedmales, CM; and 24 females, FE)were controlled in groups of 12 in pens with feeding stations allowing the recording of individual feed intake. The two vaccinations (Improvac®) were applied at a mean age of 77 and 146 days. All pigswere individually weighed every 3 weeks from the mean ages of 74 to 176 days and backfat thickness (BT) and loinmuscle depth (LD) were also recorded ultrasonically. Twelve group-housed pigs for each treatment were video recorded during 2 consecutive days at weeks 9, 11, 20, 21, 23 and 25 of age to score the number of inactive or active pigs in each treatment group by scan sampling. Aggressive behaviour by the feeder and away from the feeder, and mounting behaviour was also scored by focal sampling. Blood samples from 12 NCM, 12 CM and 12 IM were taken to determine the concentration of circulating acute phase protein Pig-MAP atweeks 1, 2, 4, 11, 13, 21 and 25 of age. After slaughter, the number of skin lesions on the left half carcasswas scored. IMpresented overall a higher growth rate and daily feed intake compared to NCM (Pb0.05),whereas their feed conversion ratios did not differ significantly. In comparison with CM, IM presented a better feed conversion ratio (Pb0.05), since their overall dailyweight gaindid not differ significantly, butIM ate less. Final leanmeat percentage of IM and CM was lower compared to that of NCM (Pb0.05). Activity, mounting and aggressive behaviour of NCM was higher than in IM, CM and FE after the second vaccination. Pig-MAP concentrationswere significantly elevated just after surgical castrationand after bothadministrations of the vaccine (Pb0.05), but concentrations subsequently decreased throughout time. Skin lesions of NCM were significantly higher compared to that of IM and FE (Pb0.05). The effects of vaccination were especially remarkable after the second dose, when the higher feed intake and lower activity of IM compared to NCMmight result in higher final body weight and more fat. Results from this study indicate that some welfare aspects such as a reduced aggression and mounting behaviour may be improved by vaccination against GnRH, together with productive benefits like adequate feed conversion ratio and daily weight gain.

Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.

BACKGROUND: Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem. We investigated the safety and efficacy of CYT006-AngQb-a vaccine based on a virus-like particle-that targets angiotensin II to reduce ambulatory blood pressure. METHODS: In this multicentre, double-blind, randomised, placebo-controlled phase IIa trial, 72 patients with mild-to-moderate hypertension were randomly assigned with a computer-generated randomisation list to receive subcutaneous injections of either 100 mug CYT006-AngQb (n=24), 300 mug CYT006-AngQb (24), or placebo (24), at weeks 0, 4, and 12. 24-h ambulatory blood pressure was measured before treatment and at week 14. The primary outcomes were safety and tolerability. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00500786. FINDINGS: Two patients in the 100 mug group, three in the 300 mug group, and none in the placebo group discontinued study treatment. All patients were included in safety analyses; efficacy analyses did not include the five dropouts, for whom no data were available at week 14. Five serious adverse events were reported (two in the 100 mug group, two in the 300 mug group, and one in the placebo group); none were deemed to be treatment related. Most side-effects were mild, transient reactions at the injection site. Mild, transient influenza-like symptoms were seen in three patients in the 100 mug group, seven in the 300 mug group, and none in the placebo group. In the 300 mug group, there was a reduction from baseline in mean ambulatory daytime blood pressure at week 14 by -9.0/-4.0 mm Hg compared with placebo (p=0.015 for systolic and 0.064 for diastolic). The 300 mug dose reduced the early morning blood-pressure surge compared with placebo (change at 0800 h -25/-13 mm Hg; p<0.0001 for systolic, p=0.0035 for diastolic). INTERPRETATION: Immunisation with CYT006-AngQb was associated with no serious adverse events; most observed adverse events were consistent with local or systemic responses similar to those seen with other vaccines. The 300 mug dose reduced blood pressure in patients with mild-to-moderate hypertension during the daytime, especially in the early morning. FUNDING: Cytos Biotechnology AG.

IPH response to Phase 2 of the New Strategic Direction for Alcohol and Drugs 2011-2016 (Northern Ireland)

The IPH response to the New Strategic Direction for Alcohol and Drugs questionnaire which has been designed to help stakeholders respond to New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) consultation document.

Cellulose acetate as solid phase in ELISA for plague

Antigen from Yersinia pestis was adsorbed on cellulose acetate discs (0.5 cm of diameter) which were obtained from dialysis membrane by using a paper punch. ELISA for human plague diagnosis was carried out employing this matrix and was capable to detect amount of 1.3 µg of antigen, 3,200 times diluted positive serum using human anti-IgG conjugate diluted 1:4,000. No relevant antigen lixiviation from the cellulose acetate was observed even after washing the discs 15 times. The discs were impregnated by the coloured products from the ELISA development allowing its use in dot-ELISA. Furthermore, cellulose acetate showed a better performance than the conventional PVC plates.

Narcolepsy and familial advanced sleep-phase syndrome: molecular genetics of sleep disorders.

Sleep disorders are very prevalent and represent an emerging worldwide epidemic. However, research into the molecular genetics of sleep disorders remains surprisingly one of the least active fields. Nevertheless, rapid progress is being made in several prototypical disorders, leading recently to the identification of the molecular pathways underlying narcolepsy and familial advanced sleep-phase syndrome. Since the first reports of spontaneous and induced loss-of-function mutations leading to hypocretin deficiency in human and animal models of narcolepsy, the role of this novel neurotransmission pathway in sleep and several other behaviors has gained extensive interest. Also, very recent studies using an animal model of familial advanced sleep-phase syndrome shed new light on the regulation of circadian rhythms.

New Strategic Direction for Alcohol & Drugs Phase 2 Second Update Report (June 2014) (PDF 1MB)

This second annual report provides an update of progress against the outcomes and indicators set out in NSD Phase 2.

New Strategic Direction for Alcohol and Drugs Phase 2 Update Report (March 2013) (PDF 652KB)

Update Report on NSD for Alcohol and Drugs Phase 2 - March 2013

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - (December 2011) (PDF 886 KB)

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - A framework for Reducing Alcohol and Drug Related Harm in Northern Ireland (December 2011)

Hybrid Multiscale Finite Volume method for two-phase flow in porous media

We present a novel hybrid (or multiphysics) algorithm, which couples pore-scale and Darcy descriptions of two-phase flow in porous media. The flow at the pore-scale is described by the Navier?Stokes equations, and the Volume of Fluid (VOF) method is used to model the evolution of the fluid?fluid interface. An extension of the Multiscale Finite Volume (MsFV) method is employed to construct the Darcy-scale problem. First, a set of local interpolators for pressure and velocity is constructed by solving the Navier?Stokes equations; then, a coarse mass-conservation problem is constructed by averaging the pore-scale velocity over the cells of a coarse grid, which act as control volumes; finally, a conservative pore-scale velocity field is reconstructed and used to advect the fluid?fluid interface. The method relies on the localization assumptions used to compute the interpolators (which are quite straightforward extensions of the standard MsFV) and on the postulate that the coarse-scale fluxes are proportional to the coarse-pressure differences. By numerical simulations of two-phase problems, we demonstrate that these assumptions provide hybrid solutions that are in good agreement with reference pore-scale solutions and are able to model the transition from stable to unstable flow regimes. Our hybrid method can naturally take advantage of several adaptive strategies and allows considering pore-scale fluxes only in some regions, while Darcy fluxes are used in the rest of the domain. Moreover, since the method relies on the assumption that the relationship between coarse-scale fluxes and pressure differences is local, it can be used as a numerical tool to investigate the limits of validity of Darcy's law and to understand the link between pore-scale quantities and their corresponding Darcy-scale variables.

Is real GDP stationary? Evidence from a panel unit root test with cross-sectional dependence and historical data

We use historical data that cover more than one century on real GDP for industrial countries and employ the Pesaran panel unit root test that allows for cross-sectional dependence to test for a unit root on real GDP. We find strong evidence against the unit root null. Our results are robust to the chosen group of countries and the sample period. Key words: real GDP stationarity, cross-sectional dependence, CIPS test. JEL Classification: C23, E32

Detection of the acute phase of abdominal angiostrongyliasis with a parasite-specific IgG enzyme linked immunosorbent assay

Angiostrongylus costaricensis may cause intestinal lesions of varied severity when it accidentally infects man in Central and South America. First-stage larvae have never been detected in stools. Therefore, a parasite-specific IgG ELISA was evaluated for the determination of the acute phase of infection. The specificity and the sensitivity of the immunoassay was shown to be 76.2% and 91.1%, respectively. Eight serum samples taken from patients with histopathological diagnosis, at different time points (3 to 15 months) after surgical treatment, showed a sharp and early decline in antibody reactivity. The titration of anti-A. costaricensis antibodies has proved to be a useful method for the diagnosis of acute abdominal angiostrongyliasis.

The candidate tuberculosis vaccine Mtb72F/AS02 in PPD positive adults: A randomized controlled phase I/II study.

Prevention of tuberculosis (TB) through vaccination would substantially reduce the global TB burden. Mtb72F/AS02 is a candidate TB vaccine shown to be immunogenic and well tolerated in PPD-negative adults. We evaluated the safety and immunogenicity of Mtb72F/AS02 in Mycobacterium-primed adults (BCG-vaccinated, or infected adults who had received post-exposure chemoprophylaxis or treatment for pulmonary TB disease). In this observer-blind controlled trial, 20 BCG-vaccinated adults and 18 adults previously infected with Mycobacterium tuberculosis (Mtb), were randomized 3:1 to receive three doses of Mtb72F/AS02 or AS02 at one-month intervals, and followed for 6 months post third vaccination. Mtb72F/AS02 was well tolerated in BCG-vaccinated adults, and tended to be more reactogenic in Mtb-infected adults. Adverse events were mainly self-limiting, resolving without sequelae. No serious adverse events were reported. The adverse events in Mtb72F/AS02 vaccinees were not clearly associated with vaccine-induced responses (as assessed by proinflammatory cytokines, total IgE and C-reactive protein levels). No Th2 T-cell responses, or vaccine-induced T-cell responses to Mtb antigens (CFP-10/PPD/ESAT-6) were detected by ICS. In both cohorts, Mtb72F/AS02 induced persistent polyfunctional Mtb72F-specific CD4(+) T-cell responses and anti-Mtb72F humoral responses. IFN-γ was detectable in serum one day post each vaccination. Further evaluation of the candidate vaccine, Mtb72F/AS02, is warranted. Trial registration: ClinicalTrials.gov identifier: NCT00146744.

In Bacillus subtilis W23, the duet sigmaXsigmaM, two sigma factors of the extracytoplasmic function subfamily, are required for septum and wall synthesis under batch culture conditions.

The synthesis of poly(RboP), the main Bacillus subtilis W23 teichoic acid, is encoded by tarDF-tarABIJKL operons, the latter being controlled by two promoters designated PtarA-int and PtarA-ext. Analysis by lacZ fusions reveals that PtarA-int activity exhibits sharp increases at the beginning and end of the transition between exponential and stationary growth phase. As confirmed by mRNA quantification, these increases are mediated by ECF sigma factors sigmaX and sigmaM respectively. In liquid media, strain W23 sigX sigM double mutants experience serious difficulties in the transition and stationary growth phases. Inactivation of sigmaX- and sigmaM-controlled regulons, which precludes transcription from PtarA-int, leads to (i) delays in chromosome segregation and septation and (ii) a transient loss of up to 30% of the culture OD or lysis. However, specific inactivation of PtarA-int, leading mainly to a shortage of poly(RboP), does not affect growth while, nevertheless, interfering with normal septation, as revealed by electron microscopy. The different sigM transcription in strains W23 and 168 is discussed. In W23, expression of tarA and sigM, which is shown to control divIC, is inversely correlated with growth rate, suggesting that the sigM regulon is involved in the control of cell division.