Measurement of the atmospheric neutrino-induced upgoing muon flux using MACRO

We present a measurement of the flux of neutrino-induced upgoing muons (~100 GeV) using the MACRO detector. The ratio of the number of observed to expected events integrated over all zenith angles is 0.74 +/- 0.036 (stat) +/- 0.046(systematic) +/- 0.13 (theoretical). The observed zenith distribution for -1.0 < cos(theta) < -0.1 does not fit well with the no oscillation expectation, giving a maximum probability for chi^2 of 0.1%. The acceptance of the detector has been extensively studied using downgoing muons, independent analyses and Monte-Carlo simulations. The other systematic uncertainties cannot be the source of the discrepancies between the data and expectations. We have investigated whether the observed number of events and the shape of the zenith distribution can be explained by a neutrino oscillation hypothesis. Fitting either the flux or zenith distribution independently yields mixing parameters of sin^2 (2theta)=1.0 and delta m^2 of a few times 10^-3 eV^2. However, the observed zenith distribution does not fit well with any expectations giving a maximum probability for chi^2 of 5% for the best oscillation hypothesis, and the combined probability for the shape and number of events is 17%. We conclude that these data favor a neutrino oscillation hypothesis, but with unexplained structure in the zenith distribution not easily explained by either the statistics or systematics of the experiment.Comment: 7 pages (two-column) with 4 figure

Consensus standards of healthcare for adults and children with inflammatory bowel disease in the UK

Objective Symptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models. Design Led by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi. Results Consensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework. Conclusions The Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD

The calcium looping cycle for CO2 capture from power generation, cement manufacture and hydrogen production

Calcium looping is a CO2 capture scheme using solid CaO-based sorbents to remove CO2 from flue gases, e.g., from a power plant, producing a concentrated stream of CO2 (∼95%) suitable for storage. The scheme exploits the reversible gas-solid reaction between CO2 and CaO(s) to form CaCO3(s). Calcium looping has a number of advantages compared to closer-to-market capture schemes, including: the use of circulating fluidised bed reactors-a mature technology at large scale; sorbent derived from cheap, abundant and environmentally benign limestone and dolomite precursors; and the relatively small efficiency penalty that it imposes on the power/industrial process (i.e., estimated at 6-8 percentage points, compared to 9.5-12.5 from amine-based post-combustion capture). A further advantage is the synergy with cement manufacture, which potentially allows for decarbonisation of both cement manufacture and power production. In addition, a number of advanced applications offer the potential for significant cost reductions in the production of hydrogen from fossil fuels coupled with CO2 capture. The range of applications of calcium looping are discussed here, including the progress made towards demonstrating this technology as a viable post-combustion capture technology using small-pilot scale rigs, and the early progress towards a 2MW scale demonstrator. © 2010 The Institution of Chemical Engineers

FokI-dCas9 mediates high-fidelity genome editing in pigs

Friday, October 11, 2019 Oral Abstracts Session 200 on PERV. Abstract #326.5Nella Fisicaro, Evelyn J. Salvaris, Gayle K. Philip, Matthew J. Wakefield, Mark B. Nottle, Wayne J. Hawthorne, Peter Cowa

FokI-dCas9 mediates high-fidelity genome editing in pigs

Brief communicationGene editing using clustered regularly interspaced short palindromic repeats/Cas9 has great potential for improving the compatibility of porcine organs with human recipients. However, the risk of detrimental off-target mutations in gene-edited pigs remains largely undefined. We have previously generated GGTA1 knock-in pigs for xenotransplantation using FokI-dCas9, a variant of Cas9 that is reported to reduce the frequency of off-target mutagenesis. In this study, we used whole genome sequencing (WGS) and optimized bioinformatic analysis to assess the fidelity of FokI-dCas9 editing in the generation of these pigs. Genomic DNA was isolated from porcine cells before and after gene editing and sequenced by WGS. The genomic sequences were analyzed using GRIDSS variant-calling software to detect putative structural variations (SVs), which were validated by PCR of DNA from knock-in and wild-type pigs. Platypus variant-calling software was used to detect single-nucleotide variations (SNVs) and small insertions/deletions (indels). GRIDSS analysis confirmed the precise integration of one copy of the knock-in construct in the gene-edited cells. Three additional SVs were detected by GRIDSS: deletions in intergenic regions in chromosome 6 and the X chromosome and a duplication of part of the CALD1 gene on chromosome 18. These mutations were not associated with plausible off-target sites, and were not detected in a second line of knock-in pigs generated using the same pair of guide RNAs, suggesting that they were the result of background mutation rather than off-target activity. Platypus identified 1375 SNVs/indels after quality filtering, but none of these were located in proximity to potential off-target sites, indicating that they were probably also spontaneous mutations. This is the first WGS analysis of pigs generated from FokI-dCas9-edited cells. Our results demonstrate that FokI-dCas9 is capable of high-fidelity gene editing with negligible off-target or undesired on-target mutagenesis.Nella Fisicaro, Evelyn J. Salvaris, Gayle K. Philip, Matthew J. Wakefield, Mark B. Nottle, Wayne J. Hawthorne, Peter J. Cowa

Human islets express a marked proinflammatory molecular signature prior to transplantation

In the context of islet transplantation, experimental models show that induction of islet intrinsic NF-κB-dependent proinflammatory genes can contribute to islet graft rejection. Isolation of human islets triggers activation of the NF-κB and mitogen-activated kinase (MAPK) stress response pathways. However, the downstream NF-κB target genes induced in human islets during the isolation process are poorly described. Therefore, in this study, using microarray, bioinformatic, and RTqPCR approaches, we determined the pattern of genes expressed by a set of 14 human islet preparations. We found that isolated human islets express a panel of genes reminiscent of cells undergoing a marked NF-κB-dependent proinflammatory response. Expressed genes included matrix metallopeptidase 1 (MMP1) and fibronectin 1 (FN1), factors involved in tissue remodeling, adhesion, and cell migration; inflammatory cytokines IL-1β and IL-8; genes regulating cell survival including A20 and ATF3; and notably high expression of a set of chemokines that would favor neutrophil and monocyte recruitment including CXCL2, CCL2, CXCL12, CXCL1, CXCL6, and CCL28. Of note, the inflammatory profile of isolated human islets was maintained after transplantation into RAG(-/-) recipients. Thus, human islets can provide a reservoir of NF-κB-dependent inflammatory factors that have the potential to contribute to the anti-islet-graft immune response. To test this hypothesis, we extracted rodent islets under optimal conditions, forced activation of NF-κB, and transplanted them into allogenic recipients. These NF-κB activated islets not only expressed the same chemokine profile observed in human islets but also struggled to maintain normoglycemia posttransplantation. Further, NF-κB-activated islets were rejected with a faster tempo as compared to non-NF-κB-activated rodent islets. Thus, isolated human islets can make cell autonomous contributions to the ensuing allograft response by elaborating inflammatory factors that contribute to their own demise. These data highlight the potential importance of islet intrinsic proinflammatory responses as targets for therapeutic intervention.Mark J. Cowley, Anita Weinberg, Nathan W. Zammit, Stacey N. Walters, Wayne J. Hawthorne ... Shane T. Grey ... et al

Introduction to the special issue on employment discrimination against immigrants

Purpose - This editorial aims to introduce the special issue on employment discrimination against immigrants. Design/methodology/approach - The first part is a commentary on key issues in the study of employment discrimination against immigrants. The second part presents the five articles in the special issue. Findings - The papers in this special issue focus on a variety of issues associated with employment discrimination against immigrants. For example, they consider: discrimination based on accents; differences among justice perceptions among immigrants and non-immigrants; the effects of negative stereotypes on workplace outcomes; the treatment of Hispanic immigrants; and the reasons for the lack of research on Hispanic immigrants. Research limitations/implications - The author comments on key issues that researchers of employment discrimination against immigrants have to take into account. These issues include: the appreciation of the diversity among immigrants; an understanding of the complexity of employment discrimination research; openness to cross-disciplinary approaches; and the consideration of employment discrimination within the context of the immigrant experience. The five articles that make up the special issues vary in their nature (empirical, critical), methodologies (quantitative, qualitative), locations (United States, Germany, and Canada), and implications. Practical implications - The issues discussed in the papers have important implications for understanding and overcoming employment discrimination against immigrants. Originality/value - The Journal of Managerial Psychology invited this special issue to initiate psychological research on employment discrimination against immigrants. The intent is to draw the attention of organizational scholars to the large, yet under-studied immigrant segment of the workforce