Using citizen science to understand floating plastic debris distribution and abundance: A case study from the North Cornish coast (United Kingdom).

Citizen science is now commonly employed to collect data on plastic pollution and is recognised as a valuable tool for furthering our understanding of the issue. Few studies, however, use citizen science to gather information on water-borne plastic debris. Here, citizen scientists adopted a globally standardised methodology to sample the sea-surface for small (1-5 mm) floating plastic debris off the Cornish coast (UK). Twenty-eight trawls were conducted along five routes, intersecting two Marine Protected Areas. Of the 509 putative plastic items, fragments were most common (64 %), then line (19 %), foam (7 %), film (6 %), and pellets (4 %). Fourier-transform infrared spectroscopy identified the most common polymer type as polyethylene (31 %), then nylon (12 %), polypropylene (8 %), polyamide (5 %) and polystyrene (3 %). This study provides the first globally comparative baseline of floating plastic debris for the region (mean: 8512 items km-2), whilst contributing to an international dataset aimed at understanding plastic abundance and distribution worldwide.

Selective RET Inhibitors (SRIs) in Cancer: A Journey from Multi-Kinase Inhibitors to the Next Generation of SRIs.

RET is a receptor tyrosine kinase that plays an important role in the development of neurons and kidneys. The gene encoding the rearranged-during-transfection (RET) receptor tyrosine kinase was first discovered in the 1980s. Activating RET mutations and rearrangements have since been identified as actionable drivers of oncogenesis in numerous cancer types and are most prevalent in thyroid and non-small-cell lung cancer. Following the modest success of repurposed RET-active multikinase inhibitors, the first selective RET inhibitors (SRIs), selpercatinib and pralsetinib, received regulatory approval in 2020. Now, thousands of patients with RET-altered cancers have benefited from first-generation SRIs, with impressive deep and durable responses. However, following prolonged treatment with these SRIs, a number of acquired on-target resistance mutations have been identified together with other non-RET-dependent resistance mechanisms. Today, the focus is on how we can further evolve and improve the treatment of RET-altered tumors with next-generation SRIs, and a number of candidate drugs are in development. The ideal next-generation SRIs will be active against on-target acquired resistance alterations, including those that emerge in the CNS, and will have improved safety and tolerability relative to first-generation SRIs. In this review, we will provide an update on these candidates and their potential to meet the unmet clinical need for patients who progress on first-generation SRIs.

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL (n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3-5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.

Developing a digital learning version of a mentorship training programme.

This article describes the experience of one university team in developing, delivering and evaluating an online Nursing and Midwifery Council-approved mentorship programme for nurses and midwives who support pre-registration students in practice. Although the authors are confident of the quality of the educational provision, this article does not discuss this programme as an exemplar of best practice, but aims to share the learning gained from the experience of introducing a digital learning version of a mentorship course.

Support for mentors-an exploration of the issues.

Nursing and midwifery mentors are fundamental to the process of ensuring future practitioners are adequately prepared and supported during the practice element of their degrees. However, there is evidence to suggest that the infrastructure and support for the mentoring role is not always adequate. This article provides a review of some of the issues including the emotional labour associated with supporting pre-registration students, difficulties in accessing protected learning time for mentoring, and lack of supportive networks for mentors to develop within the role. The authors make recommendations on what is required to ensure that the mentor role is better acknowledged, supported and resourced.

Managers' role in maximising investment in continuing professional education.

Healthcare organisations face the challenge of delivering care in increasingly complex environments. To do so they depend on competent professionals, and continuing professional education (CPE) plays a major part in ensuring that staff maintain and develop their knowledge and skills. However, there is limited evidence of the effect of CPE on healthcare outcomes, and an emphasis on outcomes has overlooked the contribution of the processes that underlie effective CPE. This article reports the results of a study that explored a range of stakeholders' perceptions of the processes that maximise the positive effects of CPE on practice. Analysis of results shows that CPE can help improve care when supported by positive organisational cultures, effective partnership working between stakeholders and supportive learning environments that enable individuals to maximise their learning. This article discusses how managers play a pivotal role in creating positive cultures in which CPE can flourish by being role models and change agents, ensuring organisational strategic objectives are aligned with personal development plans, and by working collaboratively with education colleagues to ensure that learning from CPE is embedded in practice.

The value of Master's degrees for registered nurses.

The value of graduates in the nursing workforce has been recognised in the move to all-graduate preparation of pre-registration nurses in England ( Nursing and Midwifery Council, 2010 ). Increasingly, after registration continuing professional development programmes for nurses are being offered at Master's level. However, there is limited evidence of the relationship between postgraduate study and improved patient outcomes. Evidence that does exist suggests that nurses who engage in postgraduate study are more likely to have improved critical thinking and decision-making skills, demonstrate leadership qualities to empower them to challenge poor practice, and have the skills needed for advanced clinical practice roles. This article explores these issues and makes recommendations for further work in this area.

Involving patients in the assessment of nursing students.

Enabling patients, service users and carers to participate in the education of students in the healthcare sector is widely espoused, both in the literature and by professional regulatory bodies. This article focuses on one aspect of this: the issue of patient involvement in the assessment of nursing students in the practice setting. The challenges and complexities that may arise are explored, and recommendations are made for further work in this area.

A collaborative approach to support trainee sign-off mentors.

Supervising student practitioners remains an important part of the work of registered nurses, midwives and specialist community practitioners. The Nursing and Midwifery Council (NMC) introduced sign-off mentors in 2006. Sign-off mentors are required to make decisions about whether a final placement student has achieved the required standards of proficiency for entry to the NMC register. Existing, experienced mentors who wish to become sign-off mentors must be supervised signing off final placement students on NMC-approved courses on at least three occasions by a practitioner with existing sign-off mentor status. This article describes a collaborative citywide approach to the preparation and support of sign-off mentors in Leeds.

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Roles and responsibilities of the student nurse mentor: an update.

Facilitating the learning of student nurses in the workplace is an integral role of the registered nurse. This article aims to provide an overview of the role and responsibilities of the mentor in supporting pre-registration nursing students in clinical practice. The professional obligations for the mentor to meet the Nursing and Midwifery Council (NMC) standards (NMC, 2008a) will be explored, including the ongoing requirements to keep up to date in mentoring practices. Some of the challenges within the role will be identified, including the importance of recognizing and supporting the failing student. Recent changes to the preparation requirements for sign-off mentors will be discussed. The article concludes by presenting the potential benefits to both the individual and the practice placement provider.

Process validation and screen reproducibility in high-throughput screening.

The use of large-scale compound screening has become a key component of drug discovery projects in both the pharmaceutical and the biotechnological industries. More recently, these activities have also been embraced by the academic community as a major tool for chemical genomic activities. High-throughput screening (HTS) activities constitute a major step in the initial drug discovery efforts and involve the use of large quantities of biological reagents, hundreds of thousands to millions of compounds, and the utilization of expensive equipment. All these factors make it very important to evaluate in advance of the HTS campaign any potential issues related to reproducibility of the experimentation and the quality of the results obtained at the end of these very costly activities. In this article, the authors describe how GlaxoSmithKline (GSK) has addressed the need of a true validation of the HTS process before embarking in full HTS campaigns. They present 2 different aspects of the so-called validation process: (1) optimization of the HTS workflow and its validation as a quality process and (2) the statistical evaluation of the HTS, focusing on the reproducibility of results and the ability to distinguish active from nonactive compounds in a vast collection of samples. The authors describe a variety of reproducibility indexes that are either innovative or have been adapted from generic medical diagnostic screening strategies. In addition, they exemplify how these validation tools have been implemented in a number of case studies at GSK.

Degrees of confidence.

This article explores how quality care has become a reality for older people in Lincoln and how continuing professional development (CPD) has made a real difference to patient care, and has supported the career development of two nurses working with older people at Lincoln County Hospital.

Professional development for registered nurses.

There is increasing recognition that health professionals should engage in continuing professional development and lifelong learning. In addition, planned changes to pre-registration nurse education mean that many registered nurses are considering, or will consider, further academic study. This article aims to demystify academic terminology and provide practical guidance on preparing for and accessing higher education.