Spectroscopic Studies Of Metal Binding To Metallothioneins

Metallothioneins (MT) are a class of cysteine-rich proteins that bind a wide variety of metal ions. Although it has been suggested that the structure of the metal binding sites in Cd,Zn-MT involves two metal clusters (alpha and beta) which coordinate the metals through a tetrahedral arrangement of cysteine residues, considerably less information is available concerning the metal binding sites in MT containing Hg(\u272+) and Cu(\u27+). In this work, absorption, circular dichroism and magnetic circular dichroism spectroscopies have been used to characterize metal binding to metallothioneins. Three species of MT (rat, guinea pig and crab) have been studied. In addition to the metal binding properties of MT itself, changes in the spectroscopic properties when the Cd(\u272+) and Zn(\u272+) of the native protein are replaced by Hg(\u272+) and Cu(\u27+) in vitro have also been investigated. Although the MCD spectra of the Cd,Zn-MT from all three species resemble each other closely, the CD spectra indicate a difference in the protein conformation in the crab protein. However, all three species behave in a similar manner to protonation and metal loading with Cd(\u272+). A comparison of the MCD spectra of Cd,Zn-MT with that obtained for a Cd-BAL (BAL = 2,3-dimercaptopropanol) model complex suggests that the Cd(\u272+) bound in MT has a tetrahedral symmetry.;Spectral changes observed during metal replacement studies with Hg(\u272+) and Cu(\u27+) clearly demonstrate that first Zn(\u272+) and then Cd(\u272+) ions are displaced from the MT. The following order of binding in the two clusters can be concluded from this study: Alpha cluster: Hg \u3e Cd \u3e Cu \u3e Zn; Beta cluster: Cu,Hg \u3e Cd \u3e Zn.;Titration studies of Cd,Zn-MT with Hg(\u272+) show the isomorphous replacement of Cd(\u272+) and Zn(\u272+). A comparison of the MCD spectra obtained from the Hg-substituted MT and a Hg-BAL model complex suggests that the Hg(\u272+) ions bound to the protein are not in a tetrahedral environment.;Titration studies with Cu(\u27+) show that at least four Cu(\u27+) ions can be bound to the alpha fragment, while a total of six Cu(\u27+) ions are associated with the beta domain. The MCD data indicate that the Cu(\u27+) is not bound with a tetrahedral symmetry

An exploratory study to identify risk factors for the development of capecitabine-induced Palmar Plantar Erythrodysesthesia (PPE)

Background Previous literature showed contradictory evidence on the subject of predictors of chemotherapy-induced Palmar Plantar Erythrodysesthesia (PPE). While there is evidence to suggest that dose and schedule of the drugs play a large role, the fact that many still go on to develop severe PPE following dose reduction would indicate that there are other factors involved. Since the incidence of PPE is more prevalent during the first three cycles of treatment this would also indicate that there are factors other than a cumulative effect. The contradictory evidence in the literature relates to biographical factors, performance status, co-morbidities and renal function. There is a lack of empirical evidence to support the theory that PPE is caused by damage to the microcapillaries due to everyday activities that cause friction or pressure to the hands or feet. Purpose The aim of this exploratory study was to identify pre-treatment risk factors for the development of PPE prior to cycle four. Patients and methods The study was made up of two phases, a retrospective phase and a prospective phase, using mixed strategies to collect data. Thus providing two independent samples to compare and validate or refute results. Phase I A retrospective notes review of patients who had received Infusional 5FU or capecitabine containing regimes over a 1 year period (n=392). Phase II Prospective data collection from participants receiving capecitabine monotherapy (n = 125). Data was collected during semi-structured interviews, from participant’s diaries, physical examination of the hands and feet and notes review. Data relating to activities that cause friction, pressure or heat were collected during this phase. Data from both samples were analysed independently using bivariate (chi-square and t-test) tests where each independent variable was analysed against PPE. The variables which achieved statistical significance were entered into a multivariate (binary logistic regression) model. The multivariate analysis employed a specific modelling algorithm using a relaxed alpha value applied to various entry methods to produce multiple models. The outcomes from these models were entered into a ROC curve test to establish which model was the best predictor of PPE. Results Phase I The bivariate analysis demonstrated that those at most risk of developing PPE prior to cycle 4 of capecitabine monotherapy were males with non-metastatic colorectal cancer, who had either developed PPE with previous chemotherapy regimes or not had previous chemotherapy and who started their treatment during the winter months. When variables were combined in a multivariate logistic regression model, those that were associated with an increased risk of PPE were male, no metastatic spread, no inflammatory condition as co morbidity, smoked, did not drink, had weight loss prior to treatment, a low/normal pre treatment ALP level and started their treatment during the winter. Phase II The bivariate analysis demonstrated that those at most risk of developing PPE prior to cycle 4 of capecitabine monotherapy were those with no metastatic disease, had an inflammatory condition as co morbidity, were receiving capecitabine as adjuvant treatment, had a good performance status (0-1) and had a tendency to have warm hands. When variables were combined in a multivariate logistic regression model, those that were associated with an increased risk of PPE were younger (< 65) had no metastatic disease, an inflammatory condition as co morbidity, drank alcohol regularly, had a good performance status, had not received previous radiotherapy, were overweight or obese, had a pre treatment creatinine clearance of 30-50mls/min and had a tendency to have warm hands. Conclusions Similarly to the literature, contradictory findings were seen between the two samples within this study. There was only one variable that was associated with the development of PPE prior to cycle 4, which was the absence of metastatic disease. Limitations of retrospective data may explain variation in some variables which may have been underreported; however it is likely that it is not possible to identify specific factors that increase the risk of PPE. This is the first study to have collected and analysed data related to friction, pressure and heat causing activities. These activities have been suggested as increasing the risk of developing PPE and form the basis of patient education to avoid these activities. Data from this study indicates that only a tendency to have warm hands is associated with an increased risk of PPE. Whilst this finding would need validating in larger studies, it is a unique contribution to the body of knowledge of PPE. This finding indicates that avoidance of activities that cause friction and pressure has no evidence base. Patients may therefore be avoiding activities that add to their enjoyment which at this stressful time in their lives may add to any psychological distress. Despite limitations of this study, the importance of the findings presented here lie in its usefulness in shaping future research to investigate identified variables, where before no direction was available.Hope for Cancer Smith & Nephew Foundatio

Chef image's influence on tourists' dining experiences

Highlights • Tourists’ teppanyaki restaurant dining experience is examined. • A chef’s image has a positive influence on experiential value. • Interaction with other customers positively influences experiential value. • Service quality has a positive influence on diners’ experiential value

Protocol for a feasibility study incorporating a randomised pilot trial with an embedded process evaluation and feasibility economic analysis of ThinkCancer!: a primary care intervention to expedite cancer diagnosis in Wales

Abstract Background Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. Methods The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. Discussion This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. Trial registration ClinicalTrials.gov NCT04823559. </jats:sec

Strengthening Mental Abilities with Relational Training (SMART) in Multiple Sclerosis (MS): Study protocol for a feasibility randomised controlled trial

Background Multiple sclerosis (MS) is a chronic condition of the central nervous system, affecting around 1 in every 600 people in the UK, with 130 new diagnoses every week. Cognitive difficulties are common amongst people with MS, with up to 70% experiencing deficits in higher-level brain functions—such as planning and problem-solving, attention, and memory. Cognitive deficits make it difficult for people with MS to complete everyday tasks and limit their abilities to work, socialise, and live independently. There is a clear need—and recognised research priority—for treatments that can improve cognitive functioning in people with MS. The absence of effective cognitive interventions exacerbates burdens on the services accessed by people with MS—requiring these services to manage sequelae of untreated cognitive deficits, including reduced quality of life, greater disability and dependence, and poorer adherence to disease-modifying treatments. Our planned research will fill the evidence gap through developing—and examining the feasibility of trialling—a novel online cognitive rehabilitation programme for people with MS (SMART). The SMART programme directly trains relational skills (the ability to flexibly relate concepts to one another) based on theory that these skills are critical to broader cognitive functioning. Methods The primary objective of this study aims to conduct a feasibility study to inform the development of a definitive trial of SMART for improving cognitive functioning in people with MS. The secondary objective is to develop the framework for a cost-effectiveness analysis alongside a definitive trial, and the exploratory objective is to assess the signal of efficacy. Discussion As a feasibility trial, outcomes are unlikely to immediately effect changes to NHS practice. However, this is a necessary step towards developing a definitive trial—and will give us a signal of efficacy, a prerequisite for progression to a definitive trial. If found to be clinically and cost-effective, the latter trial could create a step-change in MS cognitive rehabilitation—improving service delivery and optimising support with limited additional resources

Usability and acceptability of a cognitive training intervention (SMART) for people with multiple sclerosis (MS): A prefeasibility formative evaluation version 1; peer review: awaiting peer review

Background: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the central nervous system (CNS), increasing in incidence and prevalence across both developed and developing countries. Cognitive difficulties are common in MS sufferers with 70% experiencing difficulties in higher-level brain functioning such as planning, attention, problem solving, and memory. Computerised cognitive training programmes may hold promise as a treatment option for improving cognitive function in people with MS, subject to exploring and addressing potential barriers to usability and acceptability. Methods: This study aimed to test the usability and acceptability of a computerised cognitive training intervention—Strengthening Mental Abilities Through Relational Training (SMART) —for people with MS, through a mostly qualitative prefeasibility design (n= 12). There were two phases of testing: (1) initial usability testing via a think-aloud protocol (n= 6) and (2) alpha-testing to assess experienced acceptability over a four-week period of engagement (n= 6). Data from the two phases were subjected to Framework Analysis, wherein we deductively applied the Health IT Usability Evaluation Model and Theoretical Framework of Acceptability to assess usability and acceptability, respectively. Results: Results show SMART to have satisfactory usability with participants reacting positively to the formatting, visuality, and process of the interface. Minor suggestions were made on how best to adapt SMART for people with MS, but the programme and facilitative support were generally perceived to be acceptable, with participants expressing positive feelings about taking part in the intervention, despite associated burdens. Conclusions: This prefeasibility study provides preliminary evidence of the usability and acceptability of SMART as a computerised cognitive training programme for people with MS. We conclude that we can now move forward with a feasibility trial of SMART, with the intention of proceeding to a definitive trial with cost-effectiveness analysis. Keyword

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Overview of the assessment practices of occupational therapists working in Quebec

Description. L'évaluation du client est primordiale dans la pratique de l'ergothérapie, notamment pour établir les priorités de traitement et pour vérifier l'efficacité des interventions. Les pratiques évaluatives des ergothérapeutes sont cependant peu documentées. But. Dresser un portrait des pratiques évaluatives des ergothérapeutes du Québec selon les dimensions personne-environnement-occupation et les clientèles. Méthodologie. Une enquête transversale a été réalisée à l'aide d'un sondage en ligne envoyé aux ergothérapeutes du Québec. Résultats. En pédiatrie, les ergothérapeutes utilisent majoritairement des outils standardisés des aptitudes physiques et neurologiques. L'évaluation d'adultes cible principalement les aptitudes physiques et la productivité. Auprès des aînés, l'évaluation repose surtout sur les aspects fonctionnels, particulièrement les aptitudes physiques, les soins personnels et la sécurité à domicile, et sur le dépistage des difficultés cognitives. Implications pour la pratique. L'évaluation ergothérapique serait généralement axée sur les aptitudes physiques. Pour assurer une approche holistique, l'occupation et l'environnement devraient être davantage considérés dans l'évaluation.Abstract : Background. In occupational therapy practice, client assessments are essential for establishing treatment priorities and determining the effectiveness of interventions. However, occupational therapists' assessment practices are not well documented. Purpose. This work aimed to provide an overview of the assessment practices of Quebec occupational therapists based on the person–environment–occupation components and clienteles. Method. A cross-sectional survey was conducted using an online survey that was sent to occupational therapists in Quebec. Findings. In paediatrics, occupational therapists tend to use standardized tools to assess physical and neurological abilities. Adult assessment focuses mainly on physical abilities and productivity. For seniors, assessment focuses mainly on functional aspects (physical abilities, personal care, and home safety) and screening for cognitive difficulties. Implications. Occupational therapy assessment mostly focuses on physicial abilities. To ensure a holistic approach, more occupational and environmental components should be included in the assessment practices

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4