Tracking of Salmonella through the Pork Slaughter Process

End of project reportTo help address the problem of salmonellosis in the Republic of Ireland (RoI), a national Salmonella control programme was introduced in 1997 with a view to reducing the prevalence of Salmonella in pigs on the farm and on pig carcasses. The primary objective of this present study was to determine the correlation between the Salmonella serological and bacteriological status of pigs presented for slaughter and the Salmonella status of pork cuts following slaughter, dressing and chilling. Two additional studies investigated the prevalence and numbers of Salmonella spp. in the boning halls of four commercial pork abattoirs and at retail level in butcher shops and supermarkets in the RoI. The results indicated that categorisation of pig herds on the basis of a historical serological test for Salmonella was not a good predictor of the bacteriological Salmonella status of individual pigs at time of slaughter. However, it is acknowledged that serological testing does help in giving a rough estimate of the overall Salmonella status of a pig herd. There was a linear correlation between prevalence of Salmonella in caecal contents and on pork cuts at factory level; therefore, if the number of herds presented for slaughter with high levels of Salmonella (category 3) was reduced, there would be less potential for contamination of the lairage, equipment etc. and so less likelihood of Salmonella contamination on pork. The impact of crosscontamination during transport, lairage, processing and distribution cannot be ignored and measures to diminish this would significantly reduce the dissemination of Salmonella in the chain and the consequent risk posed. A key finding was the considerable variation in the incidence of Salmonella on different sampling days and in different slaughter plants.National Development Plan 2007-201

Construct Validity of Dimensions of Adaptive Behavior: A Multitrait-Multimethod Evaluation.

The construct validity of four dimensions of adaptive and maladaptive behavior was investigated using the multitrait-multimethod matrix procedure of Campbell and Fiske (1959). Measures off our traits cognitive competence, social competence, social maladaption, and personal maladaption were obtained on a sample of 157 persons with moderate, severe, or profound mental retardation using each of three methods of measurement-standardized assessment instrument, day shift staff ratings, and evening shift staff ratings. Applying the Campbell and Fiske rules of thumb and recently proposed structural equation modeling techniques to the data demonstrated strong convergent validity, clear discriminant validity, and only moderate levels of method variance in the observed measures. implications of the results for the assessment of adaptive behavior and its dimensional structure were discussed

Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach

Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify the small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1 × 10<sup>11</sup> vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Fidelity monitoring across the seven studies in the Consortium of Hospitals Advancing Research on Tobacco (CHART)

Background This paper describes fidelity monitoring (treatment differentiation, training, delivery, receipt and enactment) across the seven National Institutes of Health-supported Consortium of Hospitals Advancing Research on Tobacco (CHART) studies. The objectives of the study were to describe approaches to monitoring fidelity including treatment differentiation (lack of crossover), provider training, provider delivery of treatment, patient receipt of treatment, and patient enactment (behavior) and provide examples of application of these principles. Methods Conducted between 2010 and 2014 and collectively enrolling over 9500 inpatient cigarette smokers, the CHART studies tested different smoking cessation interventions (counseling, medications, and follow-up calls) shown to be efficacious in Cochrane Collaborative Reviews. The CHART studies compared their unique treatment arm(s) to usual care, used common core measures at baseline and 6-month follow-up, but varied in their approaches to monitoring the fidelity with which the interventions were implemented. Results Treatment differentiation strategies included the use of a quasi-experimental design and monitoring of both the intervention and control group. Almost all of the studies had extensive training for personnel and used a checklist to monitor the intervention components, but the items on these checklists varied widely and were based on unique aspects of the interventions, US Public Health Service and Joint Commission smoking cessation standards, or counselor rapport. Delivery of medications ranged from 31 to 100 % across the studies, with higher levels from studies that gave away free medications and lower levels from studies that sought to obtain prescriptions for the patient in real world systems. Treatment delivery was highest among those studies that used automated (interactive voice response and website) systems, but this did not automatically translate into treatment receipt and enactment. Some studies measured treatment enactment in two ways (e.g., counselor or automated system report versus patient report) showing concurrence or discordance between the two measures. Conclusions While fidelity monitoring can be challenging especially in dissemination trials, the seven CHART studies used a variety of methods to enhance fidelity with consideration for feasibility and sustainability. Trial registration - Dissemination of Tobacco Tactics for hospitalized smokers. Clinical Trials Registration No. NCT01309217. - Smoking cessation in hospitalized smokers. Clinical Trials Registration No. NCT01289275. - Using “warm handoffs” to link hospitalized smokers with tobacco treatment after discharge: study protocol of a randomized controlled trial. Clinical Trials Registration No. NCT01305928. - Web-based smoking cessation intervention that transitions from inpatient to outpatient. Clinical Trials Registration No. NCT01277250. - Effectiveness of smoking-cessation interventions for urban hospital patients. Clinical Trials Registration No. NCT01363245. - Comparative effectiveness of post-discharge interventions for hospitalized smokers. Clinical Trials Registration No. NCT01177176. - Health and economic effects from linking bedside and outpatient tobacco cessation services for hospitalized smokers in two large hospitals. Clinical Trials Registration No. NCT01236079

Full Lensing Analysis of Abell 1703: Comparison of Independent Lens-Modelling Techniques

The inner mass-profile of the relaxed cluster Abell 1703 is analysed by two very different strong-lensing techniques applied to deep ACS and WFC3 imaging. Our parametric method has the accuracy required to reproduce the many sets of multiple images, based on the assumption that mass approximately traces light. We test this assumption with a fully non-parametric, adaptive grid method, with no knowledge of the galaxy distribution. Differences between the methods are seen on fine scales due to member galaxies which must be included in models designed to search for lensed images, but on the larger scale the general distribution of dark matter is in good agreement, with very similar radial mass profiles. We add undiluted weak-lensing measurements from deep multi-colour Subaru imaging to obtain a fully model-independent mass profile out to the virial radius and beyond. Consistency is found in the region of overlap between the weak and strong lensing, and the full mass profile is well-described by an NFW model of a concentration parameter, $c_{\rm vir}\simeq 7.15\pm0.5$ (and $M_{vir}\simeq 1.22\pm0.15 \times 10^{15}M_{\odot}/h$). Abell 1703 lies above the standard $c$--$M$ relation predicted for the standard $\Lambda$CDM model, similar to other massive relaxed clusters with accurately determined lensing-based profiles.Comment: 12 pages, 17 figures, 1 table, accepted for publication in MNRAS. V2 includes minor changes and revised figure

Combined strong and weak lensing analysis of 28 clusters from the Sloan Giant Arcs Survey

We study the mass distribution of a sample of 28 galaxy clusters using strong and weak lensing observations. The clusters are selected via their strong lensing properties as part of the Sloan Giant Arcs Survey (SGAS) from the Sloan Digital Sky Survey (SDSS). Mass modelling of the strong lensing information from the giant arcs is combined with weak lensing measurements from deep Subaru/Suprime-cam images to primarily obtain robust constraints on the concentration parameter and the shape of the mass distribution. We find that the concentration c_vir is a steep function of the mass, c_vir \propto M_vir^-0.59\pm0.12, with the value roughly consistent with the lensing-bias-corrected theoretical expectation for high mass (10^15 h^-1 M_sun) clusters. However, the observationally inferred concentration parameters appear to be much higher at lower masses (10^14 h^-1 M_sun), possibly a consequence of the modification to the inner density profiles provided by baryon cooling. The steep mass-concentration relation is also supported from direct stacking analysis of the tangential shear profiles. In addition, we explore the two-dimensional shape of the projected mass distribution by stacking weak lensing shear maps of individual clusters with prior information on the position angle from strong lens modelling, and find significant evidence for a large mean ellipticity with the best-fit value of e = 0.47 \pm 0.06 for the mass distribution of the stacked sample. We find that the luminous cluster member galaxy distribution traces the overall mass distribution very well, although the distribution of fainter cluster galaxies appears to be more extended than the total mass.Comment: 29 pages, 15+9 figures, 7 tables, accepted for publication in MNRA

Strong-Lensing Analysis of a Complete Sample of 12 MACS Clusters at z>0.5: Mass Models and Einstein Radii

We present the results of a strong-lensing analysis of a complete sample of 12 very luminous X-ray clusters at $z>0.5$ using HST/ACS images. Our modelling technique has uncovered some of the largest known critical curves outlined by many accurately-predicted sets of multiple images. The distribution of Einstein radii has a median value of \simeq28\arcsec (for a source redshift of $z_{s}\sim2$), twice as large as other lower-$z$ samples, and extends to 55\arcsec for MACS J0717.5+3745, with an impressive enclosed Einstein mass of $7.4\times10^{14} M_{\odot}$. We find that 9 clusters cover a very large area (>2.5 \sq \arcmin) of high magnification ($\mu > \times10$) for a source redshift of $z_{s}\sim8$, providing primary targets for accessing the first stars and galaxies. We compare our results with theoretical predictions of the standard $\Lambda$CDM model which we show systematically fall short of our measured Einstein radii by a factor of $\simeq1.4$, after accounting for the effect of lensing projection. Nevertheless, a revised analysis once arc redshifts become available, and similar analyses of larger samples, are needed in order to establish more precisely the level of discrepancy with $\Lambda$CDM predictions.Comment: Accepted for publication in MNRAS, 19 pages, 35 figures, 2 tables. V2 includes several changes, mainly additional discussion of the results. A higher resolution version is available at ftp://wise-ftp.tau.ac.il/pub/adiz/macs1

Sunyaev Zel'dovich Effect Observations of Strong Lensing Galaxy Clusters: Probing the Over-Concentration Problem

We have measured the Sunyaev Zel'dovich (SZ) effect for a sample of ten strong lensing selected galaxy clusters using the Sunyaev Zel'dovich Array (SZA). The SZA is sensitive to structures on spatial scales of a few arcminutes, while the strong lensing mass modeling constrains the mass at small scales (typically < 30"). Combining the two provides information about the projected concentrations of the strong lensing clusters. The Einstein radii we measure are twice as large as expected given the masses inferred from SZ scaling relations. A Monte Carlo simulation indicates that a sample randomly drawn from the expected distribution would have a larger median Einstein radius than the observed clusters about 3% of the time. The implied overconcentration has been noted in previous studies with smaller samples of lensing clusters. It persists for this sample, with the caveat that this could result from a systematic effect such as if the gas fractions of the strong lensing clusters are substantially below what is expected.Comment: submitte

Cluster-Cluster Lensing and the Case of Abell 383

Extensive surveys of galaxy clusters motivate us to assess the likelihood of cluster-cluster lensing (CCL), namely, gravitational-lensing of a background cluster by a foreground cluster. We briefly describe the characteristics of CCLs in optical, X-ray and SZ measurements, and calculate their predicted numbers for $\Lambda$CDM parameters and a viable range of cluster mass functions and their uncertainties. The predicted number of CCLs in the strong-lensing regime varies from several ($<10$) to as high as a few dozen, depending mainly on whether lensing triaxiality bias is accounted for, through the c-M relation. A much larger number is predicted when taking into account also CCL in the weak-lensing regime. In addition to few previously suggested CCLs, we report a detection of a possible CCL in A383, where background candidate high-$z$ structures are magnified, as seen in deep Subaru observations.Comment: 9 pages, 5 figures, submitted to MNRA