Measurement of the muon antineutrino charged current single charged pion production cross-section on water and hydrocarbon with ND280

Tokai to Kamioka (T2K) is a long-baseline neutrino oscillation experiment based in Japan, performing measurements of neutrino oscillations and neutrino-nucleus interactions. Uncertainty in the modelling of neutrino-nucleus interactions on the order of GeV is a significant systematic uncertainty in T2K and other current oscillation experiments, and is set to become a limiting uncertainty in many measurements as new experiments are constructed. These uncertainties result from the difficulty in modelling the effects of the nuclear medium on the underlying neutrino interaction, where the kinematics and spatial distribution of nucleons is well understood for only the lightest nuclei. As such, a much improved understanding of nuclear effects on neutrino interactions is essential for neutrino interaction experiments of the near future. This thesis describes the first measurement of the muon anti-neutrino charged current single pion production cross-sections on water and hydrocarbon using the passive water and active scintillator targets in the T2K ND280 near detector. The cross-section is measured as a function of the outgoing pion kinematics, which depend heavily on both the underlying neutrino interaction models and nuclear state model, and can be directly measured for each event by the detector, reducing dependence on the input simulation. A novel method of collapsing a double differential cross-section measurement into two correlated single differential cross-section measurements is presented and validated for this analysis. It is hoped that this measurement will provide additional constraints on neutrino-nucleus pion production models, enabling better understanding of the shortcomings in these models and where improvements are required

Audio Tactile Maps (ATM) System for the Exploration of Digital Heritage Buildings by Visually-impaired Individuals - First Prototype and Preliminary Evaluation

P.I. Dr. Lorenzo Piccinali, Faculty of Technology, DMUNavigation within historic spaces requires analysis of a variety of acoustic, proprioceptive and tactile cues; a task that is well-developed in many visually-impaired individuals but for which sighted individuals rely almost entirely on vision. For the visually-impaired, the creation of a cognitive map of a space can be a long process for which the individual may repeat various paths numerous times. While this action is typically performed by the individual on-site, it is of some interest to investigate to what degree this task can be performed off-site using a virtual simulator. We propose a tactile map navigation system with interactive auditory display. The system is based on a paper tactile map upon which the user’s hands are tracked. Audio feedback provides; (i) information on user-selected map features, (ii) dynamic navigation information as the hand is moved, (iii) guidance on how to reach the location of one hand (arrival point) from the location of the other hand (departure point) and (iv) additional interactive 3D-audio cues useful for navigation. This paper presents an overview of the initial technical development stage, reporting observations from preliminary evaluations with a blind individual. The system will be beneficial to visually impaired visitors to heritage sites; we describe one such site which is being used to further assess our prototype

Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free.</p> <p>The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms.</p> <p>Results</p> <p>A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction.</p> <p>Conclusion</p> <p>In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.</p

Glucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studies.

BACKGROUND: Glucagon-like peptide-1 (7-36) amide (GLP-1) protects against stunning and cumulative left ventricular dysfunction in humans. The mechanism remains uncertain but GLP-1 may act by opening mitochondrial K-ATP channels in a similar fashion to ischemic conditioning. We investigated whether blockade of K-ATP channels with glibenclamide abrogated the protective effect of GLP-1 in humans. METHODS: Thirty-two non-diabetic patients awaiting stenting of the left anterior descending artery (LAD) were allocated into 4 groups (control, glibenclamide, GLP-1, and GLP-1 + glibenclamide). Glibenclamide was given orally prior to the procedure. A left ventricular conductance catheter recorded pressure-volume loops during a 1-min low-pressure balloon occlusion (BO1) of the LAD. GLP-1 or saline was then infused for 30-min followed by a further 1-min balloon occlusion (BO2). In a non-invasive study, 10 non-diabetic patients were randomized to receive two dobutamine stress echocardiograms (DSE) during GLP-1 infusion with or without oral glibenclamide pretreatment. RESULTS: GLP-1 prevented stunning even with glibenclamide pretreatment; the Δ % dP/dtmax 30-min post-BO1 normalized to baseline after GLP-1: 0.3 ± 6.8 % (p = 0.02) and GLP-1 + glibenclamide: -0.8 ± 9.0 % (p = 0.04) compared to control: -11.5 ± 10.0 %. GLP-1 also reduced cumulative stunning after BO2: -12.8 ± 10.5 % (p = 0.02) as did GLP-1 + glibenclamide: -14.9 ± 9.2 % (p = 0.02) compared to control: -25.7 ± 9.6 %. Glibenclamide alone was no different to control. Glibenclamide pretreatment did not affect global or regional systolic function after GLP-1 at peak DSE stress (EF 74.6 ± 6.4 vs. 74.0 ± 8.0, p = 0.76) or recovery (EF 61.9 ± 5.7 vs. 61.4 ± 5.6, p = 0.74). CONCLUSIONS: Glibenclamide pretreatment does not abrogate the protective effect of GLP-1 in human models of non-lethal myocardial ischemia. Trial registration Clinicaltrials.gov Unique Identifier: NCT02128022

An integrated self-optimizing programmable chemical synthesis and reaction engine

Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25–50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules

Fitness Tradeoffs of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli

Evolutionary trade-offs occur when selection on one trait has detrimental effects on other traits. In pathogenic microbes, it has been hypothesized that antibiotic resistance trades off with fitness in the absence of antibiotic. Although studies of single resistance mutations support this hypothesis, it is unclear whether trade-offs are maintained over time, due to compensatory evolution and broader effects of genetic background. Here, we leverage natural variation in 39 extraintestinal clinical isolates of Escherichia coli to assess trade-offs between growth rates and resistance to fluoroquinolone and cephalosporin antibiotics. Whole-genome sequencing identifies a broad range of clinically relevant resistance determinants in these strains. We find evidence for a negative correlation between growth rate and antibiotic resistance, consistent with a persistent trade-off bet

A randomised controlled trial to evaluate the efficacy of a 6 month dietary and physical activity intervention for prostate cancer patients receiving androgen deprivation therapy

<p>Abstract</p> <p>Background</p> <p>Treatment with Androgen Deprivation Therapy (ADT) for prostate cancer is associated with changes in body composition including increased fat and decreased lean mass; increased fatigue, and a reduction in quality of life. No study to date has evaluated the effect of dietary and physical activity modification on the side-effects related to ADT. The aim of this study is to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition, fatigue and quality of life, typically associated with ADT.</p> <p>Methods</p> <p>Men are recruited to this study if their treatment plan is to receive ADT for at least 6 months. Men who are randomised to the intervention arm receive a home-based tailored intervention to meet the following guidelines a) ≥ 5 servings vegetables and fruits/day; b) 30%-35% of total energy from fat, and < 10% energy from saturated fat/day; c) 10% of energy from polyunsaturated fat/day; d) limited consumption of processed meats; e) 25-35 gm of fibre/day; f) alcoholic drinks ≤ 28 units/week; g) limited intake of foods high in salt and/or sugar. They are also encouraged to include at least 30 minutes of brisk walking, 5 or more days per week. The primary outcomes are change in body composition, fatigue and quality of life scores. Secondary outcomes include dietary intake, physical activity and perceived stress. Baseline information collected includes: socio-economic status, treatment duration, perceived social support and health status, family history of cancer, co-morbidities, medication and supplement use, barriers to change, and readiness to change their health behaviour. Data for the primary and secondary outcomes will be collected at baseline, 3 and 6 months from 47 intervention and 47 control patients.</p> <p>Discussion</p> <p>The results of this study will provide detailed information on diet and physical activity levels in prostate cancer patients treated with ADT and will test the feasibility and efficacy of a diet and physical activity intervention which could provide essential information to develop guidelines for prostate cancer patients to minimise the side effects related to ADT.</p> <p>Trial registration</p> <p>ISRCTN trial number ISCRTN75282423</p

Expert by Experience involvement in Mental Health Nursing Education: The co-production of standards between Experts by Experience and Academics in Mental Health Nursing

Introduction: Involving people with lived experience of mental distress in mental health nursing education has gained considerable traction yet broader implementation remains ad-hoc and tokenistic. Effective involvement requires curricula be informed by lived experience of service use. Aim: To develop standards to underpin expert by experience involvement in mental health nursing education based on lived experience of service use. Methods: Phase one used qualitative descriptive methods, involving focus groups with service users (n=50) from six countries to explore perceptions of service user involvement in mental health nursing education. Phase two utilised these findings through consensus building to co-produce standards to support Experts by Experience involvement in mental health nursing education. Results: Three themes emerged in Phase one: enablers and barriers, practical and informational support, and emotional and appraisal support. These themes underpinned development of the standards, which reflect nine processes: induction and orientation, external supervision, supportive teamwork, preparation for teaching and assessing, 'intervision', mutual mentorship, pre and post debriefing, role clarity and equitable payment. Conclusions: These standards form the framework entitled; Standards for Co-production of Education (Mental Health Nursing) (SCo-PE [MHN]). Implications for Practice The standards aim to support implementation of Expert by Experience roles in mental health nursing education