The Prevalence and Control of Bacillus and Related Spore-Forming Bacteria in the Dairy Industry

peer-reviewedMilk produced in udder cells is sterile but due to its high nutrient content, it can be a good growth substrate for contaminating bacteria. The quality of milk is monitored via somatic cell counts and total bacterial counts, with prescribed regulatory limits to ensure quality and safety. Bacterial contaminants can cause disease, or spoilage of milk and its secondary products. Aerobic spore-forming bacteria, such as those from the genera Sporosarcina, Paenisporosarcina, Brevibacillus, Paenibacillus, Geobacillus and Bacillus, are a particular concern in this regard as they are able to survive industrial pasteurization and form biofilms within pipes and stainless steel equipment. These single or multiple-species biofilms become a reservoir of spoilage microorganisms and a cycle of contamination can be initiated. Indeed, previous studies have highlighted that these microorganisms are highly prevalent in dead ends, corners, cracks, crevices, gaskets, valves and the joints of stainless steel equipment used in the dairy manufacturing plants. Hence, adequate monitoring and control measures are essential to prevent spoilage and ensure consumer safety. Common controlling approaches include specific cleaning-in-place processes, chemical and biological biocides and other novel methods. In this review, we highlight the problems caused by these microorganisms, and discuss issues relating to their prevalence, monitoring thereof and control with respect to the dairy industry.NG is funded by the Teagasc Walsh Fellowship Scheme and through the Irish Dairy Levy funded project ‘Thermodur-Out.

Validity of a three-variable juvenile arthritis disease activity score in children with new-onset juvenile idiopathic arthritis

<p>Objectives To investigate the validity and feasibility of the Juvenile Arthritis Disease Activity Score (JADAS) in the routine clinical setting for all juvenile idiopathic arthritis (JIA) disease categories and explore whether exclusion of the erythrocyte sedimentation rate (ESR) from JADAS (the ‘JADAS3’) influences correlation with single markers of disease activity.</p> <p>Methods JADAS-71, JADAS-27 and JADAS-10 were determined at baseline for an inception cohort of children with JIA in the Childhood Arthritis Prospective Study. JADAS3-71, JADAS3-27 and JADAS3-10 were determined using an identical formula but with exclusion of ESR. Correlation of JADAS with JADAS3 and single measures of disease activity/severity were determined by category.</p> <p>Results Of 956 eligible children, sufficient data were available to calculate JADAS-71, JADAS-27 and JADAS-10 at baseline in 352 (37%) and JADAS3 in 551 (58%). The median (IQR) JADAS-71, JADAS-27 and JADAS-10 for all 352 children was 11 (5.9–18), 10.4 (5.7–17) and 11 (5.9–17.3), respectively. Median JADAS and JADAS3 varied significantly with the category (Kruskal–Wallis p=0.0001), with the highest values in children with polyarticular disease patterns. Correlation of JADAS and JADAS3 across all categories was excellent. Correlation of JADAS71 with single markers of disease activity/severity was good to moderate, with some variation across the categories. With the exception of ESR, correlation of JADAS3-71 was similar to correlation of JADAS-71 with the same indices.</p> <p>Conclusions This study is the first to apply JADAS to all categories of JIA in a routine clinical setting in the UK, adding further information about the feasibility and construct validity of JADAS. For the majority of categories, clinical applicability would be improved by exclusion of the ESR.</p&gt

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Property rents in medieval English towns: Hull in the fourteenth century

This paper examines whether property rents varied within the medieval town of Hull. Scholars have been deterred from analysing medieval urban rents because of a belief that they were ‘fossilised’ from an early stage in town development, and therefore did not reflect economic forces that guided the later development of towns. Hull rents reported in the 1347 rental had been set only recently, however. Statistical analysis of these rents reveals the economic topography of the town and leads to a reconsideration of its economic development

Elicitation of expert prior opinion:application to the MYPAN trial in childhood polyarteritis nodosa

Objectives Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). Methods A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. Results A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. Conclusions We suggest that the methodological template we propose could be applied to trial design for other rare diseases

Virtual Machine Support for Many-Core Architectures: Decoupling Abstract from Concrete Concurrency Models

The upcoming many-core architectures require software developers to exploit concurrency to utilize available computational power. Today's high-level language virtual machines (VMs), which are a cornerstone of software development, do not provide sufficient abstraction for concurrency concepts. We analyze concrete and abstract concurrency models and identify the challenges they impose for VMs. To provide sufficient concurrency support in VMs, we propose to integrate concurrency operations into VM instruction sets. Since there will always be VMs optimized for special purposes, our goal is to develop a methodology to design instruction sets with concurrency support. Therefore, we also propose a list of trade-offs that have to be investigated to advise the design of such instruction sets. As a first experiment, we implemented one instruction set extension for shared memory and one for non-shared memory concurrency. From our experimental results, we derived a list of requirements for a full-grown experimental environment for further research

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing