Feasibility Phase Research Articles

Results of the feasibility phase of the managed activity graded exercise in teenagers and pre-adolescents (MAGENTA) randomised controlled trial of treatments for chronic fatigue syndrome/myalgic encephalomyelitis

BackgroundChronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) is relatively common in young people and causes significant disability. Graded exercise therapy (GET) and activity management are recommended by the National Institute for Health and Care Excellence (NICE) despite a limited evidence-base for either treatment in paediatric CFS/ME. This paper reports on feasibility and acceptability measures from the feasibility phase of the ongoing MAGENTA randomised controlled trial (RCT) investigating GET versus activity management for young people with CFS/ME.MethodsSetting: Three specialist secondary care National Health Service (NHS) Paediatric CFS/ME services (Bath, Cambridge and Newcastle).Participants: Young people aged 8–17 years with a diagnosis of mild to moderate CFS/ME. Young people were excluded if they were severely affected, referred to cognitive behavioural therapy (CBT) at initial assessment or unable to attend clinical sessions.Interventions: GET and activity management delivered by physiotherapists, occupational therapists, nurses and psychologists. Families and clinicians decided the number (typically 8–12) and frequency of appointments (typically every 2–6 weeks).Outcome Measures: Recruitment and follow-up statistics. We used integrated qualitative methodology to explore the feasibility and acceptability of the trial processes and the interventions.Results80/161 (49.7%) of eligible young people were recruited at two sites between September 2015 and August 2016, indicating recruitment to the trial was feasible. Most recruitment (78/80; 97.5%) took place at one centre. Recruitment consultations, online consent and interventions were acceptable, with less than 10% in each arm discontinuing trial treatment. Response rate to the primary outcome (the SF36-PFS at 6 months) was 91.4%. Recruitment, treatment and data collection were not feasible at one centre. The site was withdrawn from the study.In response to data collected, we optimised trial processes including using Skype for recruitment discussions; adapting recruiter training to improve recruitment discussions; amending the accelerometer information leaflets; shortening the resource use questionnaires; and offering interventions via Skype. These amendments have been incorporated into the full trial protocol.ConclusionsConducting an RCT investigating GET versus activity management is feasible and acceptable for young people with CFS/ME.Trial registrationISRCTN23962803 https://doi.org/10.1186/ISRCTN23962803, date of registration: 03 September 2015

Randomised controlled trial comparing hydroxyapatite coated uncemented hemiarthroplasty with cemented hemiarthroplasty for the treatment of displaced intracapsular hip fractures: a protocol for the WHITE 5 study

IntroductionHip fracture is a serious injury in adults, especially those aged over 60 years. The most common type of hip fracture (displaced intracapsular) is treated for the majority of patients...

The Nutrient Trial (NUTRitional Intervention among myEloproliferative Neoplasms): Feasibility Phase

The Mediterranean diet, characterized by increased consumption of extra virgin olive oil (EVOO), nuts, legumes, vegetables, fruits, fish, and whole grain products, has proven to be beneficial in diseases where chronic subclinical inflammation plays a key role (Calder et al., 2011). For example, the PREDIMED (Prevención con Dieta Mediterránea) study demonstrated that a Mediterranean diet supplemented with EVOO or nuts reduced the incidence of major cardiovascular events (Estruch et. al, 2010). The Mediterranean diet's anti-inflammatory properties are attributed to its richness in phenolic compounds and main nutrients, such as: fiber, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, vitamins C and E, and carotenoids (Casas et al., 2017). Overproduction of pro-inflammatory cytokines like IL-6 and TNF-α is a characteristic feature of Myeloproliferative Neoplasm (MPN) and correlates with high symptom burden and may also play a role in disease progression (Craver et al., 2018). Therefore, reduction of inflammation at the early stages of disease through low-risk interventions such as diet could lessen symptom burden and potentially blunt disease progression. To date, this nutrition trial will be the first to study the effects of the Mediterranean dietary pattern in MPN patients. To initially assess the feasibility of a Mediterranean diet intervention among MPN patients, we developed a prospective interventional proof-of-concept study of 30 MPN patients randomized (1:1) to either a Mediterranean diet supplemented with EVOO or the United States Dietary Guidelines for Americans (USDA). Inclusion and exclusion criteria are listed in Table 1 and study schematic is shown in Figure 1. The primary endpoint for this study is adherence to a Mediterranean diet with our diet curriculum. Exploratory endpoints include reduction in inflammatory biomarkers, reduction in symptom burden, and change in the gut microbiome. All participants meet once at the start of the intervention period (week 3) with a dietician for one-on-one counseling to educate the participant on the central components of the Mediterranean diet or the US Dietary guidelines and tailor the diet to meet each participant's medical needs and or cultural preferences. Participants are emailed 10 weekly installments of educational materials on their respective diet. At weeks 3 and 9, participants in the Mediterranean diet arm are given 750ml of EVOO and participants in the USDA arm receive a $10 grocery gift card. Six unannounced surveys and 24-hour food recalls are collected throughout the duration of the 15-week study. Conformity with the Mediterranean dietary pattern is assessed by the 14-item Mediterranean diet adherence score. Symptom burden is assessed using the MPN symptom assessment form (MPN-SAF). Four biological sample data points are collected during the 15-week study which includes collection of blood, stool, and urine. Complete blood count, Comprehensive Metabolic Panel, Lipid Panel, hsCRP are measured, and plasma is stored for cytokine analysis. Urine is used to quantify urine total polyphenol excretion. Stool samples are used to measure changes in the gut microbiome with diet. Since opening in October 2018, we have screened 44 potential participants. Four did not meet the inclusion criteria, 8 participants did not respond to initial surveys, and thus, did not progress to the intervention phase and were not randomized. Of the 32 participants who were randomized, 2 withdrew due to family illness. Eighteen participants have completed the 15-week study and 12 participants are currently in the active intervention phase. Demographics of the 30 participants who have completed this study or are currently receiving active intervention are shown in Table 2. In summary, this is a feasibility study to evaluate if MPN patients can adhere to a Mediterranean diet when given written curriculum and verbal counseling, and to explore whether a diet rich in anti-inflammatory properties can improve MPN symptoms. Geography was a limitation for this study, participants who were not in Southern California found it difficult to arrange travel for in-person visits. Patients who self-referred were more responsive and engaged than those recruited from clinic. Subsequent trials will test the impact of diet in a larger group of MPN patients, likely with a remotely administered intervention to obviate the need for travel. Disclosures Scherber: Incyte: Consultancy; Blueprint: Other: Ad board; Gilead: Consultancy. Mesa:Genotech: Research Funding; Celgene: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Incyte: Research Funding; Samus: Research Funding; Novartis: Consultancy; La Jolla Pharma: Consultancy; AbbVie: Research Funding; Sierra Onc: Consultancy. Fleischman:incyte: Speakers Bureau.

The Adaptation and Feasibility of Narrative Enhancement and Cognitive Therapy (NECT) for Late-Onset Psychosis

The aim of this study is to adapt and feasibility test the narrative component of Narrative Enhancement and Cognitive Therapy (NECT) for late-onset psychosis. This study followed the development and feasibility phases of the Medical Research Council framework. The original NECT intervention was adapted based on consultations with service users, experts, and clinicians. The evaluation of the feasibility test of the adapted intervention was guided by Orsmond and Cohn (Occup Particip Health 35(3):169–177, 2015)’s model for feasibility studies. The final adaptations consist of language, readability, and delivery. The adapted intervention was tested for feasibility and acceptability with one group of five patients recruited from a National Health Service (NHS) Trust in UK Results were mixed in participant outcomes and a likelihood of acceptability of the intervention. This indicates the need for a larger scale feasibility test to explore the identified benefits and challenges of implementing NECT in NHS or community settings for late-onset psychosis.

Wirebond Solution of Semiconductor IC Package through Modeling and Simulation

This technical paper presents a study of wirebond selection highlighting the package electrical modeling and simulation done for semiconductor integrated circuit (IC) leadframe package (hereinafter referred to as Device Z) with different wirebond configurations: Gold 2N 1.3 mil, Gold 4N 1.3 mil, Copper 1.3 mil, Copper 1.2 mil, Copper 1.1 mil and Copper 1.0 mil. Package design, modeling and simulation are essentially important in the early stage of the package development, particularly at the package feasibility phase. 
 As Device Z is previously assembled with Gold 4N 1.3 mil wirebond configuration, this technical paper focused in determining the best alternative for Gold 4N 1.3 mil in wirebonding through package modeling and simulation. Statistical analysis reinforced the study to verify the trend and to check if there is significant statistical difference in the resistance, inductance and capacitance (hereinafter referred to as RLC) performance of the device given the different wirebond configurations. Cost analysis was crucial to determine the cost impact of using different wires.
 Prioritizing the wirebond thickness and cost without sacrificing the electrical performance, Copper 1.1 mil would be the most suitable replacement for Gold 4N 1.3 mil wirebond configuration. However, since Copper 1.1 mil is not yet available in the market, Copper 1.2 mil could be used, with better electrical parameters. In addition, Copper wire offered significant cost improvement over its Gold counterpart. Computed cost per unit of Copper 1.3 mil is just 6% of the total cost of the Gold 4N 1.3 mil – that is 94% cost savings. Ultimately, Copper wire technology offers significant cost savings and could pave the way for more businesses in the plant.

Fast Array Response Adjustment With Phase-Only Constraint: A Geometric Approach

This paper presents a geometric approach to fast array response adjustment with phase-only constraint. The devised algorithm can precisely and rapidly adjust the array response of a given point by only tuning the excitation phases of a preassigned weight vector. We geometrically reformulate the phase-only array response adjustment as a polygon construction problem, which can be solved by edge rotation in the complex plane. On this basis, we carry out a detailed analysis of the solution of polygon construction and specify the range of the feasible phase. To avoid the undesirable pattern distortion and obtain less pattern variations in the uncontrolled region, an effective and analytical phase determination approach is presented. The proposed algorithm provides an analytical solution and guarantees a precise phase-only adjustment without pattern distortion. In addition, our algorithm does not impose any restriction on the given weight vector and has a low computational complexity. Representative examples are presented to demonstrate the effectiveness of the proposed algorithm under various situations.

Technology-Enabled Person-Centered Mental Health Services Reform: Strategy for Implementation Science.

BackgroundHealth information technologies are being rapidly developed to improve the delivery of mental health care; however, a range of facilitators, barriers, and contextual conditions can impact the adoption and sustainment of these solutions. An implementation science protocol supports researchers to achieve primary effectiveness goals in relation to mental health services reform and aids in the optimization of implementation processes to promote quality health care, prolonging sustainability.ObjectiveThe aim of this paper is to describe our implementation science protocol, which serves as a foundation by which to systematically guide the implementation of technology-enabled solutions in traditional face-to-face and Web-based mental health services, allowing for revisions over time on the basis of retrospective review and constructive feedback from the services in which the technology-enabled solutions are implemented.MethodsOur implementation science protocol comprises four phases. The primary objective of the scoping and feasibility phase (Phase 1) is to determine the alignment between the service partner and the quality improvement goals supported by the technology-enabled solution. This is followed by Phase 2, the local co-design and preimplementation phase, which aims to utilize co-design methodologies, including service pathway modelling, participatory design, and user (acceptance) testing, to determine how the solutions could be used to enhance the service. In Phase 3, implementation, the accepted solution is embedded in the mental health service to achieve better outcomes for consumers and their families as well as health professionals and service managers. Using iterative evaluative processes throughout Phase 3, the solution is continuously developed, designed, and refined during implementation to adapt to the changing needs of the stakeholders, including consumers with lived experience and their families as well as the service. Thus, the primary outcome of Phase 3 is the optimized technology-enabled solution that can be maintained in a service during the sustainment and scalability phase (Phase 4) for the purposes of mental health services reform.ResultsFunding for the protocol was provided by the Australian Government Department of Health in June of 2017 for a period of 3 years. At the time of this publication, the protocol had been initiated in 11 services, serving three populations, all of which are currently operating in Phase 3. The first results are expected to be submitted for publication in 2020.ConclusionsWith the aim of improving mental health service quality, our implementation science protocol aids in the identification of factors that predict the likelihood of implementation success, as well as the development of strategies to proactively mitigate potential barriers to achieve better implementation outcomes. Putting in place a theoretically sound implementation science protocol is essential to facilitate the uptake of novel technology-enabled solutions and evidence-based practices into routine clinical practice for the purposes of improved outcomes.

Finite Element Design of Rotor Permanent Magnet Flux Switching Machine with Arbitrary Slot, Pole and Phase Combinations

A two-dimensional finite element approach for designing RPMFS (Rotor Permanent Magnet Flux Switching) machines is presented in this paper. The proposed method enables fast, accurate and computationally efficient assessment of different RPMFS machine designs with an arbitrary number of rotor poles, stator slots and stator phases. The appropriate stator winding layout is assembled for any feasible slot, pole and phase combination by employing the winding distribution table, which contributes to automating the design process. Based on the proposed method, a program is developed using the Octave FEMM (Finite Element Method Magnetics) toolbox. The program is suited for the use in the design stage, where it is necessary to determine various machine parameters for given core dimensions, terminal voltage constraints and adopted value of current density in the conductors, while taking iron saturation effects into account. Verification was carried out by simulating torque and EMF waveforms for several RPMFS machine designs.

Bifurcation Analysis of Ion-Acoustic Superperiodic Waves in Dense Plasmas

Bifurcation analysis of ion-acoustic (IA) superperiodic waves is studied in dense plasmas composed of electrons, positrons, and positive ions. Employing bifurcation analysis of dynamical systems, all feasible phase plots including superperiodic trajectory and superhomoclinic trajectory are obtained based on positron concentration (α) and velocity (v) of IA traveling wave. Using symbolic computation, superperiodic wave solutions are obtained for ultra-relativistic environment as well as non-relativistic environment. It is discerned that positron concentration (α) affects the bifurcation of IA superperiodic waves. The results of this work may be applied to understand superperiodic wave features in cold neutron star.

Omental cystic lymphangioma mimicking cystic pancreatic tumor in a patient with multiple sclerosis on immunomodulatory therapy

The feasibility phase of the HOME (Home-Monitoing and Education) project aims to show the practical feasibility of Electroencephalography (EEG) home-monitoring using a patient-controlled mobile system. Its objective is to assess the potential diagnostic and therapeutic yields of home-monitoring compared to conventional healthcare.16 office-based practitioners chose 97 patients and recorded standard 20-minute EEGs using conventional recorders. After training, the same patients used a patient-controlled mobile dry electrode EEG system in their home environment. The practitioners in charge and two additional raters assessed all recordings. We conducted inter-rater and intra-rater comparisons between the diagnostic findings.89 patients successfully conducted home-monitoring recordings. The intra-rater comparison results for the diagnostic findings of the conventional recordings and the patient-made recordings show a fair Cohen’s kappa value (0.21). Additionally, we documented a change of patient management in 9 cases.The feasibility of EEG home-monitoring using a patient-controlled device is confirmed. The yield of EEG home-monitoring comprises information that can influence patient management.Patient-controlled EEG home-monitoring is feasible as part of routine care for neurological outpatients as its technical efficacy and practical feasibility are shown and significantly positive effects on patient management are evidenced.

The NUTRIENT Trial (NUTRitional Intervention Among myEloproliferative Neoplasms): Feasibility Phase

The NUTRIENT Trial (NUTRitional Intervention Among myEloproliferative Neoplasms): Feasibility Phase

A novel experimental thrombotic myocardial infarction and primary angioplasty model in swine.

We sought to develop a reproducible animal model for acute myocardial infarction (AMI) in adult atherosclerosis-prone pigs. A coil was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolaemic pigs and left untreated until thrombotic occlusion. Then, we crossed the thrombotic occlusion with a guidewire, followed by predilatation, thrombus visualisation with optical coherence tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularisation, we calculated the index of microcirculatory resistance (IMR). After a feasibility phase (six animals), acute thrombotic occlusion was achieved in all 20 pigs. Eighteen animals were successfully revascularised and survived until sacrifice. Thrombus formation was confirmed by OCT, measurement of thrombin-antithrombin complexes and pathology examination. Myocardial necrosis was confirmed by troponin T elevation, myocardial staining and pathology examination. Distal thrombotic embolisation and microvascular obstruction were supported by increased IMR and pathology examination. A porcine model of thrombotic occlusion AMI in miniaturised adult spontaneously atherosclerosis-prone pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty completed this model which mirrors human pathological conditions with myocardial infarction, necrosis and distal embolisation.

The Effects of Positive Affect and Episodic Future Thinking on Temporal Discounting and Healthy Food Demand and Choice Among Overweight and Obese Individuals: Protocol for a Pilot 2×2 Factorial Randomized Controlled Study.

BackgroundUnhealthy behaviors (eg, poor food choices) contribute to obesity and numerous negative health outcomes, including multiple types of cancer and cardiovascular and metabolic diseases. To promote healthy food choice, diet interventions should build on the dual-system model to target the regulation and reward mechanisms that guide eating behavior. Episodic future thinking (EFT) has been shown to strengthen regulation mechanisms by reducing unhealthy food choice and temporal discounting (TD), a process of placing greater value on smaller immediate rewards over larger future rewards. However, these interventions do not target the reward mechanisms that could support healthy eating and strengthen the impact of EFT-anchored programs. Increasing positive affect (PosA) related to healthy food choices may target reward mechanisms by enhancing the rewarding effects of healthy eating. An intervention that increases self-regulation regarding unhealthy foods and the reward value of healthy foods will likely have a greater impact on eating behavior compared with interventions focused on either process alone.ObjectiveThis study aimed to introduce a protocol that tests the independent and interactive effects of EFT and PosA on TD, food choice, and food demand in overweight and obese adults.MethodsThis protocol describes a factorial, randomized, controlled pilot study that employs a 2 (affective imagery: positive, neutral) by 2 (EFT: yes, no) design in which participants are randomized to 1 of 4 guided imagery intervention arms. In total, 156 eligible participants will complete 2 lab visits separated by 5 days. At visit 1, participants complete surveys; listen to the audio guided imagery intervention; and complete TD, food demand, and food choice tasks. At visit 2, participants complete TD, food demand, and food choice tasks and surveys. Participants complete a daily food frequency questionnaire between visits 1 and 2. Analyses will compare primary outcome measures at baseline, postintervention, and at follow-up across treatment arms.ResultsFunding notification was received on April 27, 2017, and the protocol was approved by the institutional review board on October 6, 2017. Feasibility testing of the protocol was conducted from February 21, 2018, to April 18, 2018, among the first 32 participants. As no major protocol changes were required at the end of the feasibility phase, these 32 participants were included in the target sample of 156 participants. Recruitment, therefore, continued immediately after the feasibility phase. When this manuscript was submitted, 84 participants had completed the protocol.ConclusionsOur research goal is to develop novel, theory-based interventions to promote and improve healthy decision-making and behaviors. The findings will advance decision-making research and have the potential to generate new neuroscience and psychological research to further understand these mechanisms and their interactions.Trial RegistrationISRCTN Registry ISRCTN11704675; http://www.isrctn.com/ISRCTN11704675 (Archived by WebCite at http://www.webcitation.org/760ouOoKG)International Registered Report Identifier (IRRID)DERR1-10.2196/12265

PT134 - Neo-adjUvant veRsus AdjuvaNt chemotherapy in upper tract Urothelial carcinoma: A feaSibility phase II randomized clinical trial (“URANUS”)

PT134 - Neo-adjUvant veRsus AdjuvaNt chemotherapy in upper tract Urothelial carcinoma: A feaSibility phase II randomized clinical trial (“URANUS”)

A novel experimental thrombotic myocardial infarction and primary angioplasty model in atherosclerotic swine

We sought to develop a reproducible, percutaneous basic science and translational animal model for the generation of thrombotic occlusion acute myocardial infarction in adult atherosclerotic pigs. A vascular coil COOK TORNADO® 38 inches (3–3.5 × 20–50 mm) was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolemic pigs and left untreated until a thrombotic intracoronary occlusion was present. After the angiographic confirmation of total occlusion, we proceeded to crossing the newly formed thrombotic occlusion with a guidewire, followed by pre-dilatation with a semi compliant balloon, thrombus visualization with Optical Coherence Tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularization, we calculated the index of microcirculatory resistance (IMR) to estimate microvascular obstruction. AMI was confirmed by ECG, biochemical, histological, macroscopic examination and TTC imaging. After feasibility phase (6 animals), acute thrombotic occlusion was achieved in 20 pigs. In total, 18 were successful revascularized and survived until the previously selected time for sacrifice. Time to occlusion after coil placement was 69 ± 29 min, thrombus formation was confirmed by OCT, thrombin-antithrombin complexes (TAT) measurements and pathology examination. Myocardial necrosis by troponin I elevation, myocardial staining and pathology examination. Distal thrombotic embolization and microvascular obstruction were supported by increased IMR and pathology examination. Thrombotic occlusion AMI in miniaturized adult spontaneously atherosclerotic pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty mirrors human pathological conditions with myocardial infarction, necrosis and distal embolization. Our model closely simulates human presentation of AMI and can be used to evaluate antithrombotic agents and primary angioplasty techniques.

DIGITALISATION IN CONSTRUCTION INDUSTRY: CONSTRUCTION PROFESSIONALS PERSPECTIVE

This study presents the result of an assessment of digitalisation within the South African construction industry from the construction professionals' perspective. The study adopted a quantitative approach through a questionnaire survey carried out among construction professionals in Gauteng Province, South Africa. Appropriate descriptive statistical tools were used in analysing the data gathered. The study revealed that the major stages of construction where digitalisation is evident are the design phase, and the feasibility phase. The major construction processes where it is mostly visible are, construction cost control, cost planning, preliminary cost estimate and building system analysis. In addition, the most significant benefits to be derived from digitalisation in the industry includes time-saving in construction projects delivery, increase productivity, increase speed of work, increase document quality, speeding up of response time, and simpler working methods. This study contributes to the body of knowledge as it reveals the happenings surrounding digitalisation within the South African construction industry; an aspect that seems to be lacking research attention.

Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies

Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies

Biosynthesized Quantum Dot Size Cu Nanocatalyst: Peroxidase Mimetic and Aqueous Phase Conversion of Fructose

AbstractEnvironmentally benign, stable quantum dot size spherical Cu particles with an average size of ∼ 4.5 nm, as measured via transmission electron microscope, were coherently tailored exploiting renewable ethno‐pharmacological Oxalis corniculata plant extract as both reducing plus capping agent. The reliable green aqueous synthesis approach completely excluded the usage of inert atmosphere and harmful chemicals including organic solvents. The ensuing cost effective Cu nanoparticles exhibited excellent intrinsic peroxidase like activity and superior nanozyme behaviour compare to earlier reports with Km value of 0.01426 M and rmax equal to 0.1399 Mmin−1 toward the oxidation of peroxidase substrate H2O2 in presence of o‐phenylenediamine, a paradigm reaction. Significantly, the as‐prepared Cu particles have been proven to be a novel catalyst for feasible selective aqueous phase conversion of fructose to levulinic acid with a maximum yield of ∼ 22.38% at 90°C in the absenteeism of prominent side product(s), auxiliaries and high temperature reaction condition. Lewis acid property and large surface area of the generated nanoscale particles attributed to their excellent catalytic potential introducing a new avenue in the continuous demand for better sensing, biomedical applications and cleaner energy production.

Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function.

An important goal of the Human Proteome Organization (HUPO) Chromosome-centric Human Proteome Project (C-HPP) is to correctly define the number of canonical proteins encoded by their cognate open reading frames on each chromosome in the human genome. When identified with high confidence of protein evidence (PE), such proteins are termed PE1 proteins in the online database resource, neXtProt. However, proteins that have not been identified unequivocally at the protein level but that have other evidence suggestive of their existence (PE2-4) are termed missing proteins (MPs). The number of MPs has been reduced from 5511 in 2012 to 2186 in 2018 (neXtProt 2018-01-17 release). Although the annotation of the human proteome has made significant progress, the "parts list" alone does not inform function. Indeed, 1937 proteins representing ∼10% of the human proteome have no function either annotated from experimental characterization or predicted by homology to other proteins. Specifically, these 1937 "dark proteins" of the so-called dark proteome are composed of 1260 functionally uncharacterized but identified PE1 proteins, designated as uPE1, plus 677 MPs from categories PE2-PE4, which also have no known or predicted function and are termed uMPs. At the HUPO-2017 Annual Meeting, the C-HPP officially adopted the uPE1 pilot initiative, with 14 participating international teams later committing to demonstrate the feasibility of the functional characterization of large numbers of dark proteins (CP), starting first with 50 uPE1 proteins, in a stepwise chromosome-centric organizational manner. The second aim of the feasibility phase to characterize protein (CP) functions of 50 uPE1 proteins, termed the neXt-CP50 initiative, is to utilize a variety of approaches and workflows according to individual team expertise, interest, and resources so as to enable the C-HPP to recommend experimentally proven workflows to the proteome community within 3 years. The results from this pilot will not only be the cornerstone of a larger characterization initiative but also enhance understanding of the human proteome and integrated cellular networks for the discovery of new mechanisms of pathology, mechanistically informative biomarkers, and rational drug targets.

Treating anxiety after stroke (TASK): the feasibility phase of a novel web-enabled randomised controlled trial

BackgroundAnxiety affects a quarter of strokes. It can be disabling even after mild stroke and transient ischaemic attack (TIA). It is not feasible to deliver conventional psychological therapies to the large population of anxious stroke and TIA patients. We are testing the feasibility of a web-enabled randomised controlled trial (RCT) to compare an individualised telemedicine cognitive behavioural therapy (CBT)-based intervention with a self-guided web-based relaxation programme. This study aims to evaluate the feasibility of novel trial procedures and the delivery of the TASK interventions in stroke and TIA patients.MethodsWe aim to recruit 40 community-based stroke and TIA patients experiencing anxiety at least 1 month post-discharge in Lothian, Scotland. We will assess the (1) recruitment number per month; (2) percentage completion of electronic consent; (3) time taken for remote eligibility confirmation; (4) percentage completion of follow-up surveys: modified Rankin scale, EuroQol-5D5L, 7-item generalised anxiety disorder, Patient Health Questionnaire-2 and modified fear questionnaire; (5) data capture of intervention fidelity and (6) use of actigraph smartwatches to obtain continuous data of rest/activity.DiscussionThe current study will provide feasibility data on streamlined web-enabled trial procedures and the use of smartwatches to obtain objective measures in stroke and TIA patients, offering potential for large efficient RCTs to be conducted centrally and remotely with far fewer resources in the future. This study will inform further refinements of the TASK interventions before evaluation in a definitive RCT.Trial registrationClinicaltrials.gov NCT03439813. Retrospectively registered on 20/2/2018.