Protocol for a feasibility study of a cohort embedded randomised controlled trial comparing NEphron Sparing Treatment (NEST) for small renal masses

Introduction: Small renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison. / Methods and analysis: Single-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians’ discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs. / Ethics and dissemination: Ethical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published. / Trial registration: ISRCTN18156881; Pre-results

Review: The increasing importance of carbon nanotubes and nanostructured conducting polymers in biosensors

The growing need for analytical devices requiring smaller sample volumes, decreased power consumption and improved performance have been driving forces behind the rapid growth in nanomaterials research. Due to their dimensions, nanostructured materials display unique properties not traditionally observed in bulk materials. Characteristics such as increased surface area along with enhanced electrical/optical properties make them suitable for numerous applications such as nanoelectronics, photovoltaics and chemical/biological sensing. In this review we examine the potential that exists to use nanostructured materials for biosensor devices. By incorporating nanomaterials, it is possible to achieve enhanced sensitivity, improved response time and smaller size. Here we report some of the success that has been achieved in this area. Many nanoparticle and nanofibre geometries are particularly relevant, but in this paper we specifically focus on organic nanostructures, reviewing conducting polymer nanostructures and carbon nanotubes

Qualified and Unqualified (N-R C) mental health nursing staff - minor differences in sources of stress and burnout. A European multi-centre study

<p>Abstract</p> <p>Background</p> <p>Unqualified/non-registered caregivers (N-R Cs) will continue to play important roles in the mental health services. This study compares levels of burnout and sources of stress among qualified and N-R Cs working in acute mental health care.</p> <p>Methods</p> <p>A total of 196 nursing staff - 124 qualified staff (mainly nurses) and 72 N-R Cs with a variety of different educational backgrounds - working in acute wards or community mental teams from 5 European countries filled out the Maslach Burnout Inventory (MBI), the Mental Health Professional Scale (MHPSS) and the Psychosocial Work Environment and Stress Questionnaire (PWSQ).</p> <p>Results</p> <p>(a) The univariate differences were generally small and restricted to a few variables. Only Social relations (N-R Cs being less satisfied) at Work demands (nurses reporting higher demands) were different at the .05 level. (b) The absolute scores both groups was highest on variables that measured feelings of not being able to influence a work situation characterised by great demands and insufficient resources. Routines and educational programs for dealing with stress should be available on a routine basis. (c) Multivariate analyses identified three extreme groups: (i) a small group dominated by unqualified staff with high depersonalization, (ii) a large group that was low on depersonalisation and high on work demands with a majority of qualified staff, and (iii) a small N-R C-dominated group (low depersonalization, low work demands) with high scores on professional self-doubt. In contrast to (ii) the small and N-R C-dominated groups in (i) and (iii) reflected mainly centre-dependent problems.</p> <p>Conclusion</p> <p>The differences in burnout and sources of stress between the two groups were generally small. With the exception of high work demands the main differences between the two groups appeared to be centre-dependent. High work demands characterized primarily qualified staff. The main implication of the study is that no special measures addressed towards N-R Cs in general with regard to stress and burnout seem necessary. The results also suggest that centre-specific problems may cause more stress among N-R Cs compared to the qualified staff (e.g. professional self-doubt).</p

Weaning practices in phenylketonuria vary between health professionals in Europe

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe

Early feeding practices in infants with phenylketonuria across Europe

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and <17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.Peer reviewe

High catalytic activity of oriented 2.0.0 copper(I) oxide grown on graphene film

[EN] Metal oxide nanoparticles supported on graphene exhibit high catalytic activity for oxidation, reduction and coupling reactions. Here we show that pyrolysis at 900 C under inert atmosphere of copper(II) nitrate embedded in chitosan films affords 1.1.1 facet-oriented copper nanoplatelets supported on few-layered graphene. Oriented (1.1.1) copper nanoplatelets on graphene undergo spontaneous oxidation to render oriented (2.0.0) copper(I) oxide nanoplatelets on few-layered graphene. These films containing oriented copper(I) oxide exhibit as catalyst turnover numbers that can be three orders of magnitude higher for the Ullmann-type coupling, dehydrogenative coupling of dimethylphenylsilane with n-butanol and C–N cross-coupling than those of analogous unoriented graphene-supported copper(I) oxide nanoplatelets.Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa and CTQ2012-32315) and Generalitat Valenciana (Prometeo 2013-019) is gratefully acknowledged. Partial financial support from European Union (Being Energy project) is also acknowledged. J.F.B. and I. E.-A. thank the Technical University of Valencia and the Spanish Ministry of Science for PhD scholarships, respectively. The authors are grateful to Mrs. Amparo Forneli for her assistance in the sample preparation and to Dr. Agouram Said from SCSIE, University of Valencia for the sample preparation and HRTEM characterization of samples. AD thanks University Grants Commission, New Delhi, for the award of Assistant Professorship under its Faculty Recharge Programme. AD also thanks Department of Science and Technology, India, for the financial support through Fast Track project (SB/FT/CS-166/2013) and the Generalidad Valenciana for financial aid supporting his stay at Valencia through the Prometeo programme. VP thanks UEFISCDI for financial support through PN-II-ID-PCE-2011-3-0060 project (275/2011).Primo Arnau, AM.; Esteve Adell, I.; Blandez Barradas, JF.; Amarajothi, D.; Alvaro Rodríguez, MM.; Candu, N.; Coman, SM.... (2015). High catalytic activity of oriented 2.0.0 copper(I) oxide grown on graphene film. Nature Communications. 6. https://doi.org/10.1038/ncomms9561S85616Huang, J. et al. Nanocomposites of size-controlled gold nanoparticles and graphene oxide: formation and applications in SERS and catalysis. Nanoscale 2, 2733–2738 (2010).Li, X., Wang, X., Song, S., Liu, D. & Zhang, H. 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Characterisation and application of a novel cell for mechanistic electrochemistry at elevated temperatures

A novel high temperature cell capable of measuring electrochemical signals up to temperatures of 115°C is reported. Characterisation of the cell has been undertaken by examining three differing systems. First the voltammetric response of a range of simple redox systems in both aqueous and non-aqueous media was recorded in order to deduce the activation energies for diffusion of these molecules. Next the steady state linear sweep voltammetric response of N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) in dimethyl sulfoxide (DMSO) is assessed as a means of studying an inferred structural change of the solvent at elevated temperatures. A change in the activation energy for diffusion from 13 kJ mol-1 to 27 kJ mol-1 was observed as the temperature was raised. Finally, the electrochemically catalysed reaction of the radical cation TMPD+ with ascorbic acid is studied from 25°C to 107°C; the corresponding kinetic parameters are deduced

Investigation into the Speciation of Inorganic Arsenic in Weakly Alkaline Medium by Voltammetry

The speciation of inorganic forms of arsenic was studied using anodic stripping voltammetry (ASV) at a gold microelectrode in conjunction with photoreduction of As(V). Sodium sulfite (0.1 M) and ammonium buffer (pH≥9.5) were selected as both background electrolyte and photo-reductive reagent. Oxygen was removed by radical chain reactions with sulfite. The proposed speciation method was validated for mixtures of arsenic As(III/V) at concentrations up to 1 mg L−1. The calculated LOD of As(III/V) was 0.06 µg L−1 (3σ, tdep 40 s). Any interference from nitrate anions present at up to millimolar concentration was minimized by their photoreduction