Optimisation of detectors for the golden channel at a neutrino factory

That neutrinos have mass and mix is now well established experimentally. Measurements of the properties of neutrinos from both natural and man-made sources have measured the large mixing angles and mass squared differences. In order to fully understand the nature of the neutrino, and ultimately the lepton sector, a number of measurements remain to be made. The Neutrino Factory would produce an intense beam of muon neutrino (muon antineutrino) and electron antineutrino (electron neutrino) from the decay of muons creating an intense flux of neutrinos. Such a facility would be capable of constraining the already measured mixing parameters to unprecedented accuracy while achieving sensitivity to the measurement of the third mixing angle and leptonic CP violating phase unrivaled by other facilities. The golden channel is characterised by the observation of a primary muon of the opposite charge to that decaying at the source, however, since this signal is subdominant the large data sample of correct sign muons have the potential to produce backgrounds to the desired signal channel and as such understanding the cross-sections to high accuracy enables a far better understanding of the response of the detector. Making these measurements requires the optimisation of all aspects of the detectors used for the measurement of the interaction properties as well as those which search for the appearance of neutrino flavours not present at the source. Pixellated silicon detectors are capable of high resolution three dimensional track reconstruction and vertexing. In studying active pixel sensors (APS) it was sought to understand the feasibility of commercially available technology to perform vertexing at a detector positioned within 1~km of the neutrino factory source. Using such technology at this near detector would improve significantly the ability of the experiment to constrain the cross-sections of neutrinos. These measurements would be particularly important in understanding neutrino induced charm production since the decays, in particular of charged D mesons, can produce penetrating muons with the potential to confuse the extraction of the appearance of muon neutrino (muon antineutrino). The capability to observe the impact parameter of the decaying meson significantly improves the accuracy of any measurement of the charm production cross-section. A Magnetised Iron Neutrino Detector (MIND) of large mass (50-100 ktonne) has been studied as the far detector where high suppression of the beam inherent backgrounds can be achieved due to the powerful suppression of hadronic particles in iron. Particular focus has been given to the introduction of a realistic reconstruction of the signal and analysis which optimises the signal efficiency below 5 GeV which has been identified by theoretical studies as key to the accurate measurement of the oscillation parameters down to low values. Studies of this detector have led to the extraction of the expected response of the detector to both golden channel signals and demonstration of the power of such an analysis to the measurement of the remaining oscillation parameters. Using minimal assumptions in the digitization of the simulated signal, the reconstruction and analysis of a large data-set of neutrino interactions, including deep-inelastic scattering (DIS), quasi-elastic scattering (QEL) and resonant pion production (RES), in MIND has led to the extraction of response matrices predicting signal efficiency for both muon neutrino and muon antineutrino appearance with thresholds between 2-3 GeV while suppressing key beam inherent backgrounds to at or below the 10^-4 level. Such a response has been shown to open the possiblity of sensitivity to the measurement of leptonic CP violation through the measurement of the mixing complex phase delta down to theta13 of order 0.2 degrees for maximal violation and to most possible values from theta13 of order 1 degrees. Sensitivity to the measurement of theta13 and to the determination of the true mass hierarchy is maintained down to theta13 of order 0.25 degrees

The cytochrome P450 family in the parasitic nematode <i>Haemonchus contortus</i>

&lt;i&gt;Haemonchus contortus&lt;/i&gt;, a highly pathogenic and economically important parasitic nematode of sheep, is particularly adept at developing resistance to the anthelmintic drugs used in its treatment and control. The basis of anthelmintic resistance is poorly understood for many commonly used drugs with most research being focused on mechanisms involving drug targets or drug efflux. Altered or increased drug metabolism is a possible mechanism that has yet to receive much attention despite the clear role of xenobiotic metabolism in pesticide resistance in insects. The cytochrome P450s (CYPs) are a large family of drug-metabolising enzymes present in almost all living organisms, but for many years thought to be absent from parasitic nematodes. In this paper, we describe the CYP sequences encoded in the &lt;i&gt;H. Contortus&lt;/i&gt; genome and compare their expression in different parasite life-stages, sexes and tissues. We developed a novel real-time PCR approach based on partially assembled CYP sequences “tags” and confirmed findings in the subsequent draft genome with RNA-seq. Constitutive expression was highest in larval stages for the majority of CYPs, although higher expression was detected in the adult male or female for a small subset of genes. Many CYPs were expressed in the worm intestine. A number of &lt;i&gt;H. Contortus&lt;/i&gt; genes share high identity with &lt;i&gt;Caenorhabditis elegans&lt;/i&gt; CYPs and the similarity in their expression profiles supports their classification as putative orthologues. Notably, &lt;i&gt;H. Contortus&lt;/i&gt; appears to lack the dramatic CYP subfamily expansions seen in &lt;i&gt;C. elegans&lt;/i&gt; and other species, which are typical of CYPs with exogenous roles. However, a small group of &lt;i&gt;H. Contortus&lt;/i&gt; genes cluster with the &lt;i&gt;C. elegans&lt;/i&gt; CYP34 and CYP35 subfamilies and may represent candidate xenobiotic metabolising genes in the parasite

Socioeconomic deprivation as measured by the index of multiple deprivation and its association with low sex hormone binding globulin in women

ACKNOWLEDGEMENTS M.L., I.L. and A.H.H. participated in the study concept and design, acquisition of data, study analysis, interpretation of data, drafting of the manuscript. D.M. provided statistical expertise. R.D., A.J.H., and A.F. participated in the interpretation of data and critical revision of the manuscript.Peer reviewedPublisher PD

Evidence from two independent backcross experiments supports genetic linkage of microsatellite Hcms8a20, but not other candidate loci, to a major ivermectin resistance locus in Haemonchus contortus

Haemonchus contortus is the leading parasitic nematode species used to study anthelmintic drug resistance. A variety of candidate loci have been implicated as being associated with ivermectin resistance in this parasite but definitive evidence of their importance is still lacking. We have previously performed two independent serial backcross experiments to introgress ivermectin resistance loci from two H. contortus ivermectin-resistant strains – MHco4(WRS) and MHco10(CAVR) – into the genetic background of the ivermectin-susceptible genome reference strain MHco3(ISE). We have interrogated a number of candidate ivermectin resistance loci in the resulting backcross populations and assessed the evidence for their genetic linkage to an ivermectin resistance locus. These include the microsatellite marker Hcms8a20 and six candidate genes Hco-glc-5, Hco-avr-14, Hco-lgc-37 (previously designated Hco-hg-1), Hco-pgp-9 (previously designated Hco-pgp-1), Hco-pgp-2 and Hco-dyf-7. We have sampled the haplotype diversity of amplicon markers within, or adjacent to, each of these loci in the parental strains and fourth generation backcross populations to assess the evidence for haplotype introgression from the resistant parental strain into the genomic background of the susceptible parental strain in each backcross. The microsatellite Hcms8a20 locus showed strong evidence of such introgression in both independent backcrosses, suggesting it is linked to an important ivermectin resistance mutation in both the MHco4(WRS) and MHco10(CAVR) strains. In contrast, Hco-glc-5, Hco-avr-14, Hco-pgp-9 and Hco-dyf-7 showed no evidence of introgression in either backcross. Hco-lgc-37 and Hco-pgp-2 showed only weak evidence of introgression in the MHco3/4 backcross but not in the MHco3/10 backcross. Overall, these results suggest that microsatellite marker Hcms8a20, but not the other candidate genes tested, is linked to a major ivermectin resistance locus in the MHco4(WRS) and MHco10(CAVR) strains. This work also emphasises the need for genome-wide approaches to identify mutations responsible for the ivermectin resistance in this parasite

Economics and gender : ways of understanding the social relations of women and men in the economy

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1988.Includes bibliographical references.by Andrew McDonald Laing.Ph.D

Understanding the Impact on Healthcare Professionals of Viewing Digital Stories of Adults with Cancer: A Hermeneutic Study

The purpose of this study was to understand the effects on oncology healthcare providers (HCPs), both personally and professionally, of watching digital stories made by adults with cancer (past and present), and what HCPs envisioned for the uses of digital stories. Seven healthcare professionals from various disciplines volunteered for this study. This research took place in a large urban center in Western Canada and was done in the tradition of philosophical hermeneutics. A 90-minute focus group was used for data collection, where participants watched eight digital stories (batched in four groups of two stories) that had been created by individuals with cancer (past or present). Data was analyzed using an interpretive qualitative methodology. Findings revealed that watching digital stories made by adults with cancer was emotionally compelling, provided context, incited deep introspection, and may offer a protective effect with respect to HCP burnout

Rapid Evaluation for health and social care innovations: Challenges for “quick wins” using interrupted time series.

Background: Rapid evaluation was at the heart of National Health Service England’s evaluation strategy of the new models of care vanguard programme. This was to facilitate the scale and spread of successful models of care throughout the health & social care system. The aim of this paper is to compare the findings of the two evaluations of the Enhanced health in Care Homes (EHCH) vanguard in Gateshead, one using a smaller data set for rapidity and one using a larger longitudinal data set and to investigate the implications of the use of rapid evaluations using interrupted time series (ITS) methods. Methods: A quasi-experimental design study in the form of an ITS was used to evaluate the impact of the vanguard on secondary care use. Two different models are presented differing by timeframes only. The short-term model consisted of data for 11 months data pre and 20 months post vanguard. The long-term model consisted of data for 23 months pre and 34 months post vanguard. Results: The cost consequences, including the cost of running the EHCH vanguard, were estimated using both a single tariff non-elective admissions methodology and a tariff per bed day methodology. The short-term model estimated a monthly cost increase of £73,408 using a single tariff methodology. When using a tariff per bed day, there was an estimated monthly cost increase of £14,315. The long-term model had, using a single tariff for non-elective admissions, an overall cost increase of £7576 per month. However, when using a tariff per bed-days, there was an estimated monthly cost reduction of £57,168. Conclusions: Although it is acknowledged that there is often a need for rapid evaluations in order to identify “quick wins” and to expedite learning within health and social care systems, we conclude that this may not be appropriate for quasi-experimental designs estimating effect using ITS for complex interventions. Our analyses suggests that care must be taken when conducting and interpreting the results of short-term evaluations using ITS methods, as they may produce misleading results and may lead to a misallocation of resources