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Purpose: Inhibition of monocarboxylate transporter (MCT) 1–mediated lactate transport may have cytostatic and/or cytotoxic effects on tumor cells. We report results from the dose-escalation part of a first-in-human trial of AZD3965, a first-in-class MCT1 inhibitor, in advanced cancer. Patients and Methods: This multicentre, phase I, dose-escalation and dose-expansion trial enrolled patients with advanced solid tumors or lymphoma and no standard therapy options. Exclusion criteria included history of retinal and/or cardiac disease, due to MCT1 expression in the eye and heart. Patients received daily oral AZD3965 according to a 3+3 then rolling six design. Primary objectives were to assess safety and determine the MTD and/or recommended phase II dose (RP2D). Secondary objectives for dose escalation included measurement of pharmacokinetic and pharmacodynamic activity. Exploratory biomarkers included tumor expression of MCT1 and MCT4, functional imaging of biological impact, and metabolomics. Results: During dose escalation, 40 patients received AZD3965 at 5–30 mg once daily or 10 or 15 mg twice daily. Treatment-emergent adverse events were primarily grade 1 and/or 2, most commonly electroretinogram changes (retinopathy), fatigue, anorexia, and constipation. Seven patients receiving ≥20 mg daily experienced dose-limiting toxicities (DLT): grade 3 cardiac troponin rise (n = 1), asymptomatic ocular DLTs (n = 5), and grade 3 acidosis (n = 1). Plasma pharmacokinetics demonstrated attainment of target concentrations; pharmacodynamic measurements indicated on-target activity. Conclusions: AZD3965 is tolerated at doses that produce target engagement. DLTs were on-target and primarily dose-dependent, asymptomatic, reversible ocular changes. An RP2D of 10 mg twice daily was established for use in dose expansion in cancers that generally express high MCT1/low MCT4).

Purpose:Inhibition of monocarboxylate transporter (MCT) 1–mediated lactate transport may have cytostatic and/or cytotoxic effects on tumor cells. We report results from the dose-escalation part of a first-in-human trial of AZD3965, a first-in-class MCT1 inhibitor, in advanced cancer.Patients and Methods:This multicentre, phase I, dose-escalation and dose-expansion trial enrolled patients with advanced solid tumors or lymphoma and no standard therapy options. Exclusion criteria included history of retinal and/or cardiac disease, due to MCT1 expression in the eye and heart. Patients received daily oral AZD3965 according to a 3+3 then rolling six design. Primary objectives were to assess safety and determine the MTD and/or recommended phase II dose (RP2D). Secondary objectives for dose escalation included measurement of pharmacokinetic and pharmacodynamic activity. Exploratory biomarkers included tumor expression of MCT1 and MCT4, functional imaging of biological impact, and metabolomics.Results:During dose escalation, 40 patients received AZD3965 at 5–30 mg once daily or 10 or 15 mg twice daily. Treatment-emergent adverse events were primarily grade 1 and/or 2, most commonly electroretinogram changes (retinopathy), fatigue, anorexia, and constipation. Seven patients receiving ≥20 mg daily experienced dose-limiting toxicities (DLT): grade 3 cardiac troponin rise (n = 1), asymptomatic ocular DLTs (n = 5), and grade 3 acidosis (n = 1). Plasma pharmacokinetics demonstrated attainment of target concentrations; pharmacodynamic measurements indicated on-target activity.Conclusions:AZD3965 is tolerated at doses that produce target engagement. DLTs were on-target and primarily dose-dependent, asymptomatic, reversible ocular changes. An RP2D of 10 mg twice daily was established for use in dose expansion in cancers that generally express high MCT1/low MCT4).

supplementary data: Methods, tables, figure.

The health of the majority of South Africa’s population is seriously threatened by hunger and micronutrient deficiency, with impaired immune response a real threat, which the current SARSCoV-2 virus pandemic has highlighted. Traditional household food-processing techniques can, amongst other advantages, increase nutrient bioavailability in affordable staple foods and hence provide a way, in part, to alleviate malnutrition for food-insecure communities. In this way, immune defence and pathogen resilience of the food insecure could be enhanced so that they can better survive both COVID-19 and future threats. [ABSTRACT FROM AUTHOR] Copyright of South African Journal of Clinical Nutrition is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5β-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these, AKR1D1-002 is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid biosynthesis. However, specific activity and expression of AKR1D1-001 and AKR1D1-006 are unknown. Expression of AKR1D1 variants were measured in human liver biopsies and hepatoma cell lines by qPCR. Their three-dimensional (3D) structures were predicted using in silico approaches. AKR1D1 variants were overexpressed in HEK293 cells, and successful overexpression confirmed by qPCR and Western blotting. Cells were treated with either cortisol, dexamethasone, prednisolone, testosterone or androstenedione, and steroid hormone clearance was measured by mass spectrometry. Glucocorticoid and androgen receptor activation were determined by luciferase reporter assays. AKR1D1-002 and AKR1D1-001 are expressed in human liver, and only AKR1D1-006 is expressed in human testes. Following overexpression, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone, testosterone or androstenedione. We have demonstrated the differential expression and role of AKR1D1 variants in steroid hormone clearance and receptor activation in vitro. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited, steroid-specific role in the regulation of dexamethasone action.

Bronchiolitis obliterans syndrome (BOS) is the most morbid form of chronic graft-versus-host disease (cGVHD) after hematopoietic cell transplantation (HCT). Progressive airway fibrosis leads to a five-year survival of 40%. Treatment options for BOS are limited. A single arm, 52-week, Phase I study of pirfenidone was conducted. The primary outcome was tolerability defined as maintaining the recommended dose of pirfenidone (2403mg/day) without a dose reduction totaling more than 21 days, due to adverse events (AEs) or severe AEs (SAEs). Secondary outcomes included pulmonary function tests (PFTs) and patient reported outcomes (PROs). Among 22 participants treated for 1-year, 13 (59%) tolerated the recommended dose, with an average daily tolerated dose of 2325.6 mg/day. Twenty-two SAEs were observed, with 90.9% related to infections, none were attributed to pirfenidone. There was an increase in the average percent predicted forced expiratory volume in 1 second (FEV(1)%) of 7 percentage points annually and improvements in PROs related to symptoms of cGVHD. In this Phase I study, treatment with pirfenidone was safe. The stabilization in PFTs and improvements in PROs suggest the potential of pirfenidone for BOS treatment and support the value of a randomized controlled trial to evaluate the efficacy of pirfenidone in BOS after HCT. CLINICAL TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT03315741).

The College of Policing has stated its intention to have policing recognised as a profession. In pursuit of this ambition, they have created a Code of Ethics and introduced a graduate entry requirement for new recruits. These changes reflect common features of established professions such as medicine and the law. Another common feature of established professions is an established body of knowledge that informs professional practice. The College has developed a Crime Reduction Toolkit as the genesis of a knowledge base for policing. The evidence presented on the toolkit is generally based on random control trials and their systematic review. While this is accords with the evidence-based approach supported by the College and others it has been criticised as being too quantitative. Some commentators have argued that it overlooks the qualitative approaches such as ethnography which have been the traditional research approach to the study of policing and ignores the voice of practitioners. It is generally accepted that to date research has had little impact on policing practice. This article argues for the adoption of a pragmatic philosophical framework for the development and application of a professional knowledge-based for policing. Pragmatic philosophy would facilitate the incorporation of both qualitative and quantitative research into the creation of a knowledgebase. Furthermore, pragmatism is an action-oriented philosophy that accords with the College of Policing’s ‘what works’ agenda, and would not only accommodate practitioner research but provides a structure for changes to current practices that are needed if the police are to become a profession

In my work, I have found that environments, such as secure mental health units, add an additional layer of complexity for the occupational therapist who seeks to understand people’s occupational experiences. I present this chapter in three parts: an introduction to secure mental health services in the United Kingdom; an outline of a framework which positions “occupational engagement” in a framework of values and consequences; and, to conclude, examples of how the framework could be used to help illuminate the dark side of occupations of men living in a forensic mental health unit.

Introduction Small cell lung cancer (SCLC) has a dismal prognosis. Circulating tumour cells (CTCs) can be used to generate CTC derived explants (CDX) for the study of SCLC biology and the development of novel therapeutics. We investigated whether there are demographic or clinical predictors of the success of CDX generation, and whether CDX models are representative of the SCLC patient population. Methods This was a single centre, retrospective analysis of SCLC patients who had participated in the CHEMORES Study. Paired blood samples were donated for CTC enumeration and CDX generation attempt at pre-treatment baseline, disease progression and intervening timepoints. Clinical and demographic data was collected from electronic records, and analysed for differences between patients whose samples did and did not generate a CDX. Results 231 paired blood samples were taken from 147 patients. 45 CDX were generated from 34 patients. CTC number was significantly higher in blood samples which successfully generated a CDX than those which didn’t, at both baseline (p=

Aldosterone is an important mineralocorticoid responsible for fluid and electrolyte homeostasis produced by aldosterone synthase (CYP11B2). An aldosterone synthase inhibitor (ASI) may be a therapeutic option for primary aldosteronism-related conditions such as resistant hypertension. An ASI with sufficient selectivity for CYP11B2 versus the similar cortisol-producing enzyme CYP11B1 has remained elusive. PB6440 is a novel ASI that is potent and highly selective for CYP11B2. In vitro studies demonstrated 200-300-fold selectivity of PB6440 for human CYP11B2 compared to human CYP11B1. In single and multiple dose cynomolgus monkey studies of orally administered PB6440, dose-and concentration-dependent reduction of plasma aldosterone after ACTH challenge was observed with >90% reduction at higher doses. Consistent with its high selectivity, PB6440 had little effect on the CYP11B1 cortisol pathway. Plasma levels of cortisol, 11-deoxycortisol, and deoxycorticosterone, remained unchanged even at high doses of PB6440. Systolic and diastolic blood pressure was reduced in a dose-dependent manner. Circulating half-life of PB6440 was approximately 17 hours with high oral bioavailability. In summary, PB6440 is a highly selective ASI that demonstrated sustained aldosterone suppression for 14 days with no effect on the CYP11B1 pathway in non-human primates. In single and multiple dose studies, PB6440 appeared well tolerated, demonstrating good oral bioavailability, and a PK profile supportive of once daily dosing. These results suggest that PB6440 may be useful in humans as a novel therapeutic for treating hypertension or other conditions caused by excess aldosterone.

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5β-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these, AKR1D1-002 is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid synthesis. However, specific activity and expression of AKR1D1-001 and AKR1D1-006 are unknown.AKR1D1-002, AKR1D1-001 and AKR1D1-006 were measured in human liver biopsies and human hepatoma cell lines by qPCR. Three-dimensional (3D) structures of AKR1D1 variants were determined using in silico approaches. AKR1D1 variants were over-expressed in HEK293 cells, and successful overexpression confirmed by qPCR and western blotting. Steroid hormone clearance was measured by mass spectrometry and ELISA, and steroid receptor activation determined by luciferase reporter assays.AKR1D1-002 and AKR1D1-001 are expressed in human liver, and only AKR1D1-006 is expressed in human testes. Following over-expression in HEK293 cells, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone or testosterone.We have demonstrated the differential expression and role of AKR1D1 splice variants to regulate steroid hormone clearance and receptor activation. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited role in the regulation of synthetic glucocorticoid action.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P

Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids.

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Purpose Facilitation of genuine occupational engagement rather than a more superficial level of participation that has minimal therapeutic benefit is a challenge within secure mental health settings. The purpose of this paper is to develop, pilot and evaluate therapeutic tools based on a framework of occupational engagement. Design/methodology/approach The study used action research with occupational therapists from two secure residential units. Focus group discussions gathered participants’ views of how the occupational engagement framework could be used to inform a therapeutic tool. Following the development and piloting of the subsequent tools, focus groups were again used to review their usefulness in practice. Discussions were audio recorded and thematically analysed. Findings Three tools were designed and piloted. Evaluation revealed a number of benefits and different ways in which the tools could be used in practice. Research limitations/implications This research has indicated that the occupational engagement framework has potential for increasing understanding of the relationship between the value and consequences of participating in occupations. The limited timescale of the research restricted the opportunity to fully explore the tools’ potential effectiveness as outcome measures. Practical implications The clinical tools developed within this research have provided some information to the clinical teams which has contributed to their understanding of how service users experience participating in occupations. Originality/value The occupational engagement framework and resulting tools have the potential to enhance understanding of occupational engagement within secure settings.

This introduction contains personal information and a summary of numerous technical achievements of Professor Philip J. Morris, an incredibly talented aeroacoustician and a true gentleman. Phil’s daughter Karen Morris, with the help of her mother Bing Morris, provided the history of Phil’s family and early education. The lead author has been an active research partner for over 30 years and the second author has been a continuing research partner for that long, including his time as Phil’s PhD advisee. The technical contributions made during Phil’s time in Toronto, Canada, and in Georgia and Pennsylvania, USA are sprinkled with personal information to round out his many accomplishments. We hope that this prosopography serves to enhance and contextualize this special journal volume compiled for Phil, an honor that is so richly deserved.

Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid tumor mass, better strategies to exploit these cells for improved cancer therapy are needed. Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. Anti-TEM8 ADC elicited potent anticancer activity through an unexpected killing mechanism we term DAaRTS (drug activation and release through stroma), whereby the tumor microenvironment localizes active drug at the tumor site. Following capture of ADC prodrug from the circulation, tumor-associated stromal cells release active MMAE free drug, killing nearby proliferating tumor cells in a target-independent manner. In preclinical studies, ADC treatment was well tolerated and induced regression and often eradication of multiple solid tumor types, blocked metastatic growth, and prolonged overall survival. By exploiting TEM8+ tumor stroma for targeted drug activation, these studies reveal a drug delivery strategy with potential to augment therapies against multiple cancer types.

Purpose Occupational therapists working in mental health services in the UK are under increasing scrutiny to provide both clinically and cost-effective services. The profession has indicated that a stronger evidence base would help promote the unique contribution of occupational therapy when influencing service managers and government bodies. The paper aims to discuss these issues. Design/methodology/approach The Royal College of Occupational Therapists (RCOT) and its Specialist Section – Mental Health carried out a survey to gauge recent research capacity among occupational therapists working in mental health services in the UK and to seek their views about how to further increase research capacity and partnerships. Findings Of the 145 participants approximately half had been involved in research in the past five years, and most had involved research partnerships. A number had successfully applied for funding and about half of the research carried out had been disseminated. The participants felt that methods to increase research capacity and partnerships should continue to include improving research leadership and networks; promoting research skills through formal studies and increasing research dissemination. Originality/value A variety of methods will continue to be required to expand the evidence base. RCOT and its Specialist Sections continue to have an important role developing research capacity and partnerships.

The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial.Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established.CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients.We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making.ClinicalTrials.gov identifier: NCT00433563.

107 Background: Saracatinib is an orally-available, highly selective inhibitor of Abl and Src family members. It is an ATP-competitive tyrosine kinase inhibitor. Preclinical data suggested that the combination of a Src kinase inhibitor and docetaxel is synergistic, and Src kinase activity was also implicated in the bone’s metabolic response to cancer metastases. Methods: Patients with mCRPC were initially enrolled in an open-label, dose escalation phase I trial of oral saracatinib (cohorts of 50mg, 125mg and 175mg daily) with docetaxel (75mg/m2) in a 3+3 design. Subsequent patients were randomised 1:1 between saracatinib 175mg and placebo once daily. Pharmacokinetics (PK) of docetaxel were explored in phase I to exclude significant drug-drug interaction. The primary endpoint of phase II was biochemical or radiographic progression free survival (PFS). Secondary endpoints included overall survival (OS), safety and tolerability. Changes in circulating tumour cell (CTC) counts were also measured. The phase II was designed with a 1-sided alpha of 0.2 with 90% power to detect a hazard ratio (HR) for PFS of 0.67. Results: 10 patients were enrolled in phase I and 142 in the randomised phase II. No dose limiting toxicities or PK interactions were observed and the recommended dose for phase II was 175mg saracatinib daily and 75mg/m2docetaxel every 21 days. In phase II, the HR for PFS was 1.35 (80% confidence interval (CI) 1.07 to 1.70). The HR for OS was 1.42 (1.08 – 1.81). 41/71 and 29/71 experienced treatment related toxicities of grade 3 or above in the saracatinib and placebo arms respectively. 10/19 (53%) and 14/27 (52%) evaluable patients demonstrated a reduction in CTCs from ≥5 to < 5 /7.5ml blood at 6 weeks after starting saracatinib and placebo respectively. Conclusions: Saracatinib, in combination with docetaxel, adds toxicity and not efficacy in mCRPC. This combination should not be developed further in combination with docetaxel in the treatment of mCRPC. Clinical trial information: ISRCTN22566729.

This paper focuses on the occupational experiences of five men living within a forensic mental health unit over a year. This study used a descriptive qualitative case study methodology to explore the meaning and value placed on daily life (activities, occupations and routines), and how this changed over time. The men’s stories showed a complex picture of their experiences of daily life. This study demonstrated the impact of the environment on the men and the ongoing challenge of the need to balance treatment/therapy with security demands and opportunities. Three interrelated themes were identified: (1) Power and Occupation; (2) Therapy or Punishment; (3) Occupational Opportunities within Restrictions. These findings serve as a reminder to clinical teams to reassess the value of occupations attributed by their patients and the impact of the secure environment, whilst also acknowledging the potential for occupations to have a negative impact on well-being.

Tumor recurrence after surgical resection of NSCLC obstructs long-term disease-free survival in approximately 50% of cases. Our data suggest that combining circulating tumor cell enumeration (as single cells or clusters) in tumor-draining pulmonary vein and peripheral blood (assessed by CellSearch) at the time of NSCLC surgery better identifies those patients at higher risk for lung cancer recurrence than does peripheral circulating tumor cell number alone.

Children with medical complexity (CMC) in rural and northern communities have more difficulty accessing subspecialty health providers than those in urban centres. This article describes an alignment cascade in which leaders engaged peers and staff to rapidly roll out the implementation of a sustainably designed complex care model, integrated in the Champlain Complex Care Program and delivered in Timmins, Ontario. The Provincial Council for Maternal and Child Health's Complex Care for Kids Ontario (CCKO) strategy supports the implementation and expansion of a hub-and-spoke model of interprofessional complex care for CMC and their families. A nurse practitioner is the primary point of contact for the family and oversees coordination and integration of care; regional CCKO programs are committed to building capacity to provide safe, high-quality care for CMC in communities closer to their homes.

Introduction: Client centred practice is seen to be vital to the occupational therapy profession (COT 2010). However, there are on going challenges to promote our professional values and meet the expectations of services and organisations. There is still a significant shift needed from therapist led sessions to truly collaborative therapy (Sumsion & Law 2006). As a result, the research considered an alternative method in the form of Performance Profiling utilised within sporting psychology (Butler & Hardy 1992).\ud \ud Method: The research used a social constructionist methodology (Burr 2003) to investigate expert occupational therapists’ perceptions of the potential of Performance Profiling within occupational therapy practice. Ethical approval was granted by the University of Cumbria. In accordance with the constructionist approach of ‘learning by making’, methods used included a workshop on Performance Profiling followed by either a focus group or an unstructured interview depending on the number of participants. Participants were asked two questions – 1. To share their thoughts about Performance Profiling and 2. Whether they thought it could support OT practice. The data were analysed thematically.\ud \ud What is Performance Profiling? Performance Profiling (Butler, 1989) has been devised as an application of Kelly’s (1955) Personal Construct Theory to sporting psychology (Doyle & Parfitt, 1997). Kelly’s (1955) Personal Construct Theory predicates on the notion people use their experiences to interpret the world, a process called construing. Performance Profiling offers a systematic method to enhance the understanding of how athletes rate their physical, psychological and technical skill development to achieve optimum performance. This supports collaboration to build optimal interventions based on the athlete’s own perception of need (Doyle & Parfitt 1997). The performance profile is utilised for the evaluation and planning of any component of performance. The technique provides understanding and quantifying perceptions of both the client and therapist. Figure 1 is a completed profile for a University student who values their sport and education. The athlete and therapist negotiated the components of successfully engaging within their sport. These were inserted into the outside ring of the template. This was then discussed to determine the athlete’s valued outcomes, current ratings (red shading) and ideal rating (think black line) of performance. Collaborative goals are then developed aimed at athlete’s ideal performance.\ud \ud Findings: Nine participants from three countries were involved in the research. Four themes were found: theoretical perspectives, practice settings, promoting communication and education. These are illustrated in the quotes in Figure 1. There was agreement that Performance Profiling had potential the use of supporting occupational therapy practice philosophy and promoting effective communication with clients. However, future research would need to consider is benefits to the client centred relationship.\ud \ud Next steps: This research was the pilot study of a UK PhD Study at the University of Cumbria. Data is currently being collected within the USA as a visiting scholar of the University of Wisconsin Milwaukee. The research next steps concern the meaning of communication within the therapeutic relationship. The research intends to be validated and formally introduced to occupational therapy practice.

Background: Schizophrenia is a severe mental health condition that is characterised by positive symptoms, such as hallucinations and delusions; negative symptoms, such as flattened affect, thought disorder (disrupted speech), and lack of motivation; and cognitive symptoms, such as problems with memory and attention. Schizophrenia can occur as an isolated episode, or as a recurring cycle of remission and relapse, and is associated with impairment in psychosocial and occupational functioning. Although antipsychotic drugs are the main treatment for people with schizophrenia, in most countries mental health services usually provide a range of add-on interventions, including occupational therapy. This is a complex intervention designed to support and enable continued participation in daily life through engagement in activities and occupations meaningful to the individual. Occupational therapists are professionals trained to deliver therapy where the emphasis is on improving occupational function and participation rather than treating symptoms, and uses a wide range of methods based on the needs of individuals. However, similar interventions may also be delivered by staff not trained as occupational therapists.\ud \ud Objectives: To examine the effects of occupational therapy delivered by occupational therapists compared to occupational therapy delivered by any other person for people with schizophrenia.\ud \ud Search methods: We searched the Cochrane Schizophrenia Group’s Study-Based Register of Trials (including trial registers) on 4 November 2016 and 26 July 2018.\ud \ud Selection criteria: All randomised controlled trials evaluating the functional or clinical outcomes of occupational therapy, or both, for people with schizophrenia delivered by occupational therapists compared with occupational therapy for people with schizophrenia delivered by anyone other than occupational therapists.\ud \ud Data collection and analysis: Review authors independently inspected citations, selected studies, extracted data, and appraised study quality.\ud \ud Main results: The search yielded 1633 records. Of these, we retrieved 17 full-text reports (14 studies) for further scrutiny, which we subsequently excluded as they did not meet our inclusion criteria.\ud \ud Authors’ conclusions: Currently there are no randomised controlled trials comparing delivery of occupational therapy for people diagnosed with schizophrenia by occupational therapists with delivery of similar interventions by anyone other than occupational therapists. Research studies employing methodologically robust trial designs are needed to establish whether or not there are better outcomes for people with a diagnosis of schizophrenia with occupational therapy that is delivered by trained occupational therapists.

Digital technologies (DTs) are increasingly prevalent in global everyday life and considered as tools to bridge health inequalities relating to the urban-rural divide. Occupational therapists can optimize the fit between people, activities and DTs, though little is known about rural practice. The study aimed to understand rural occupational therapists’ view of DT and identify its perceived impact on practice. Fourteen occupational therapists from six countries were recruited through social media and email. Data were collected through an online questionnaire and either a one-to-one interview or online group discussion. Influenced by grounded theory, the data were analyzed using thematic analysis and constant comparison with current literature. Three themes emerged: DT was identified as pervasive, having a multidimensional impact on modern rural citizenship; DT interacted with the concept of being available, regarded as complementary to face-to-face contact; and therapists engaged in dynamic technological actions and ideas responding to diverse needs. Participants embraced the changing importance of DT in their clients’ daily lives, used personalized approaches and adapted practice to the evolving DT landscape. This study indicates the profession may offer insights for health and social care providers and digital health developers. Collaboration on inclusive provision may reduce health inequalities and meet rural communities’ needs.

Introduction The purpose of this qualitative study was to explore the lived experience of cross-dressing, to raise awareness of cross-dressing and investigate any possible implications for occupational therapy. Method A single design case study utilizing an unstructured interview was used with a male cross-dresser known to the first author. Following transcription, flexible and ongoing analysis was undertaken following an interpretative phenomenological analysis approach and emergent themes resulted in an ongoing literature review. Findings The themes that developed were ‘identity’, ‘dressing’ and ‘conflict’. A complexity of meanings related to cross-dressing also emerged: uncontrollable urge; erotic expression; sexual orientation; and a sense of completeness. Conclusion The findings suggest that cross-dressing is a meaningful occupation and as such influences identity formation and occupational choices. Occupational therapists have a duty of care to this vulnerable and alienated group within society.

Occupational science is of importance to multiple disciplines due to its potential to contribute to understandings of complex social issues. “Occupation”, as a key concept of occupational science, is recognised as being highly complex, making it challenging for students to develop a comprehensive understanding of the concept. Terminology of occupational science literature has been noted at times as using the terms occupation, purposeful activity and activity interchangeably, which further adds to the challenge of teaching the concept. This paper explores evolving definitions of occupation, challenges this evolution has created within education, and the potential use of occupation as a threshold concept. Consideration of a selection of pedagogic methods used in teaching the concept of occupation is briefly explored. The paper concludes with identification of a newly developed occupation-focused teaching tool as a proposed alternative approach to teaching the concept of occupation. The teaching tool was originally developed to teach occupation as a discrete concept, rather than the therapeutic use of occupation as taught in occupational therapy education. The tool is an analogy for occupation, and has utility in supporting the transformation of students’ understanding of the concept of occupation, commensurate to understandings of occupational science.

While the College of Occupational Therapists (2013) supports interprofessional education (IPE) at the pre-registration level, a review of existing literature has indicated a variety of barriers to achieving this, particularly for post-graduate level Occupational Therapy students (Pollard et al., 2004; Howell, 2009). While IPE is addressed informally by many students on placement, little is known about this phenomenon (Pollard, 2009). Therefore, the research question seeks to discover the views and experiences of postgraduate (pre-registration) Occupational Therapy students towards informal IPE on practice placement.\ud The research aims to:\ud • discover how IPE may occur on student placements\ud • determine the value students place upon IPE \ud • identify any barriers to effective IPE for students on placement, and how these are negotiated.\ud The research question shall be addressed using a convenience sample of 4–6 MSc (pre-registration) Occupational Therapy students. Research participants shall be asked to complete a short questionnaire, followed by a focus group surveying their views and experiences of IPE on placement. Data shall be analysed using an interpretative phenomenological approach, capitalising upon the researcher’s recent practice placement experience (Shaw, 2010). The completed research article is due to be completed by 8 May 2017. It is anticipated that research findings will inform occupational therapy educators and practice placement providers when arranging and evaluating student practice placements.

“Occupational engagement” is a term often used within occupational science and occupational therapy literature. However, it has yet to be clearly and consistently described resulting in a lack of clarity in the use and definition of this term. This paper is derived from a larger piece of research, which used social constructionism to explore occupational engagement for five men living in a secure mental health unit from an occupational science perspective (Morris et al, 2016). This research required the development of a clear description of ‘occupational engagement’. Following an exploration and critical review of the literature, the process of developing a new description of ‘occupational engagement’ is outlined. Occupational engagement cannot be considered in isolation, so within this paper it is positioned within a descriptive framework of values and consequences. The development of the framework returned to the etymology of relevant terms, considering both the value of consequences of occupational experiences. This is the first published holistic description of this term as the framework fully acknowledges the negative as well as positive dimensions of occupation. The paper concludes with the implications of how this new framework could be useful to occupational science.

Our aims are to determine levels of circulating cellular and protein biomarkers in hepatocellular carcinoma (HCC) patients and to analyse any relationships with clinical parameters. Fifty-four consenting patients were recruited. Circulating tumour cells (CTCs) were enumerated (by CellSearch) and characterised via filtration [by isolation by size of epithelial tumour cells (ISET)] with downstream immunohistochemistry (IHC). Glypican-3 (GPC3) expression in tumour biopsies and CTCs (by IHC) was compared, and levels of circulating caspase-cleaved and full-length cytokeratin 18 (CK18, measured using M30 and M65 ELISAs) were examined as a putative prognostic factor and marker of tumour burden. CTCs were identified in 14 out of 50 (28 %) patients by CellSearch and in 19 out of 19 (100 %) patients by ISET. The presence of GPC3-positive CTCs by ISET was 100 % concordant with the presence of GPC3-positive cells in the original tumour (n = 5). No statistically significant correlations were observed between CTC number and clinical characteristics, although trends were noted between CTC subtypes, Child–Pugh score and tumour node metastasis stage. Serum M30 and M65 levels (as continuous variables) significantly correlated with overall survival (OS) in a univariate analysis (p = 0.003 and p

It is argued that the way in which we view a person with dementia can have a significant effect on the level of disability and wellbeing of the person. There is a divergence between a belief that the self disintegrates, leaving a non-person, and a belief that the self remains but is misplaced and can be maintained with the appropriate approach from others. This article seeks to examine the differing approaches to self and personhood in dementia care, and establish ways of approaching care for the person with dementia which may limit the extent of disability in the face of cognitive decline.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:\ud \ud To examine the effects of occupational therapy delivered by occupational therapists compared to occupational therapy delivered by any other person for people with schizophrenia. Our secondary objectives are to determine whether the response differs by specific type (e.g. hospital versus non-hosptial setting), intensity (e.g. more therapist contact time or more frequent task repetition), or duration of occupational therapy.