A feasibility, randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis (BREEZE-IPF): study protocol

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that causes breathlessness and cough that worsen over time, limiting daily activities and negatively impacting quality of life. Although treatments are now available that slow the rate of lung function decline, trials of these treatments have failed to show improvement in symptoms or quality of life. There is an immediate unmet need for evidenced-based interventions that improve patients' symptom burden and make a difference to everyday living. This study aims to assess the feasibility of conducting a definitive randomised controlled trial of a holistic, complex breathlessness intervention in people with IPF. Methods and analysis The trial is a two-centre, randomised controlled feasibility trial of a complex breathlessness intervention compared with usual care in patients with IPF. 50 participants will be recruited from secondary care IPF clinics and randomised 1:1 to either start the intervention within 1 week of randomisation (fast-track group) or to receive usual care for 8 weeks before receiving the intervention (wait-list group). Participants will remain in the study for a total of 16 weeks. Outcome measures will be feasibility outcomes, including recruitment, retention, acceptability and fidelity of the intervention. Clinical outcomes will be measured to inform outcome selection and sample size calculation for a definitive trial. Ethics and dissemination Yorkshire and The Humber – Bradford Leeds Research Ethics Committee approved the study protocol (REC 18/YH/0147). Results of the main trial and all secondary end-points will be submitted for publication in a peer-reviewed journal

Barriers and facilitators to uptake and retention of inner-city ethnically diverse women in a postnatal weight management intervention: a mixed-methods process evaluation within a feasibility trial in England.

OBJECTIVES: To understand the barriers and facilitators to uptake and retention of postnatal women randomised to a commercial group weight management intervention using the COM-B (capability, opportunity, motivation and behaviour) behaviour change model. DESIGN: Concurrent mixed-methods (qualitative dominant) process evaluation nested within a feasibility randomised controlled trial, comprising questionnaires and interviews at 6 and 12 months postbirth. SETTING: One National Health Service maternity unit in an inner city area in the south of England. PARTICIPANTS: 98 postnatal women with body mass indices>25 kg/m2 (overweight/obese) at pregnancy commencement. INTERVENTION: Twelve-week Slimming World (SW) commercial group weight management programme, commencing anytime from 8 to 16 weeks postnatally. PRIMARY AND SECONDARY OUTCOME MEASURES: Data regarding uptake and retention from questionnaires and interviews conducted 6 and 12 months postbirth analysed thematically and mapped to the COM-B model. RESULTS: Barriers to SW uptake mostly concerned opportunity issues (eg, lack of time or childcare support) though some women also lacked motivation, not feeling that weight reduction was a priority, and a few cited capability issues such as lacking confidence. Weight loss aspirations were also a key factor explaining retention, as were social opportunity issues, particularly in relation to factors such as the extent of group identity and relationship with the group consultant; and physical opportunity such as perceived support from and fit with family lifestyle. In addition, barriers relating to beliefs and expectations about the SW programme were identified, including concerns regarding compatibility with breastfeeding and importance of exercise. Women's understanding of the SW approach, and capability to implement into their lifestyles, appeared related to level of attendance (dose-response effect). CONCLUSIONS: Uptake and retention in commercial weight management programmes may be enhanced by applying behaviour change techniques to address the barriers impacting on women's perceived capability, motivation and opportunity to participate. TRIAL REGISTRATION NUMBER: ISRCTN39186148

Frobenius Splittings

We give a gentle introduction to Frobenius splittings. Then we recall a few results that have been obtained with the method.Comment: 21 pages, typos correcte

Evaluating Matrix Circuits

The circuit evaluation problem (also known as the compressed word problem) for finitely generated linear groups is studied. The best upper bound for this problem is $\mathsf{coRP}$, which is shown by a reduction to polynomial identity testing. Conversely, the compressed word problem for the linear group $\mathsf{SL}_3(\mathbb{Z})$ is equivalent to polynomial identity testing. In the paper, it is shown that the compressed word problem for every finitely generated nilpotent group is in $\mathsf{DET} \subseteq \mathsf{NC}^2$. Within the larger class of polycyclic groups we find examples where the compressed word problem is at least as hard as polynomial identity testing for skew arithmetic circuits

EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy

Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach. Patients and Methods: Fresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS). Results: 275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia. Conclusions: This study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population

Digital technologies, legal design and the future of the legal profession

Legal Technology – or “Legal Tech” – is disrupting the traditional operations and self-understanding of the legal profession. This chapter introduces the central claim of this book, namely that these developments are having and will continue to have a disruptive effect on the work of lawyers and that adapting to this new operating environment is crucial for legal professionals remaining relevant in an increasingly technology-driven world. This introductory chapter outlines some of the main features of this on-going transformation process, introduces some of the pressures it is creating for lawyers, and provides short summaries of the chapters that comprise this collection.fi=vertaisarvioitu|en=peerReviewed

Morita Equivalence, Picard Groupoids and Noncommutative Field Theories

In this article we review recent developments on Morita equivalence of star products and their Picard groups. We point out the relations between noncommutative field theories and deformed vector bundles which give the Morita equivalence bimodules.Comment: Latex2e, 10 pages. Conference Proceeding for the Sendai Meeting 2002. Some typos fixe

A proof of the Grothendieck-Serre conjecture on principal bundles over regular local rings containing infinite fields

Let R be a regular local ring, containing an infinite field. Let G be a reductive group scheme over R. We prove that a principal G-bundle over R is trivial, if it is trivial over the fraction field of R.Comment: Section "Formal loops and affine Grassmannians" is removed as this is now covered in arXiv:1308.3078. Exposition is improved and slightly restructured. Some minor correction

Formality theorems for Hochschild complexes and their applications

We give a popular introduction to formality theorems for Hochschild complexes and their applications. We review some of the recent results and prove that the truncated Hochschild cochain complex of a polynomial algebra is non-formal.Comment: Submitted to proceedings of Poisson 200