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

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

The impact of the COVID-19 pandemic on harm reduction services in Spain.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: Containment policies and other restrictions introduced by the Spanish government in response to the COVID-19 pandemic present challenges for marginalised populations, such as people who use drugs. Harm reduction centres are often linked to social services, mental health services, and infectious disease testing, in addition to tools and services that help to reduce the harms associated with injecting drugs. This study aimed to explore the impact of the pandemic on these services in four autonomous communities in Spain. - Label: METHODS NlmCategory: METHODS content: This is a cross-sectional study that employed a seven-section structured survey administered electronically to 20 centres in July 2020. Data from the most heavily affected months (March-June) in 2020 were compared to data from the same period in 2019. Averages were calculated with their ranges, rates, and absolute numbers. - Label: RESULTS NlmCategory: RESULTS content: "All 11 responding centres reported having had to adapt or modify their services during the Spanish state of alarm (14 March-21 June 2020). One centre reported complete closure for 2\xC2\xA0months and four reported increases in their operating hours. The average number of service users across all centres decreased by 22% in comparison to the same period in the previous year and the average needle distribution decreased by 40% in comparison to 2019. Most centres reported a decrease in infectious disease testing rates (hepatitis B and C viruses, human immunodeficiency virus, and tuberculosis) for March, April, and May in 2020 compared to the previous year. Reported deaths as a result of overdose did not increase during the state of alarm, but 2/11 (18%) centres reported an increase in overdose deaths immediately after finalisation of the state of alarm." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: Overall, Spanish harm reduction centres were able to continue operating and offering services by adjusting operating hours. The number of overall service users and needles distributed fell during the Spanish state of alarm lockdown period, suggesting that fewer clients accessed harm reduction services during this time, putting them at greater risk of reusing or sharing injecting equipment, overdosing, acquiring infectious diseases with decreased access to testing or discontinuing ongoing treatment such as methadone maintenance therapy, hepatitis C treatment, or antiretroviral therapy

The impact of the COVID-19 pandemic on harm reduction services in Spain

Containment policies and other restrictions introduced by the Spanish government in response to the COVID-19 pandemic present challenges for marginalised populations, such as people who use drugs. Harm reduction centres are often linked to social services, mental health services, and infectious disease testing, in addition to tools and services that help to reduce the harms associated with injecting drugs. This study aimed to explore the impact of the pandemic on these services in four autonomous communities in Spain. This is a cross-sectional study that employed a seven-section structured survey administered electronically to 20 centres in July 2020. Data from the most heavily affected months (March-June) in 2020 were compared to data from the same period in 2019. Averages were calculated with their ranges, rates, and absolute numbers. All 11 responding centres reported having had to adapt or modify their services during the Spanish state of alarm (14 March-21 June 2020). One centre reported complete closure for 2 months and four reported increases in their operating hours. The average number of service users across all centres decreased by 22% in comparison to the same period in the previous year and the average needle distribution decreased by 40% in comparison to 2019. Most centres reported a decrease in infectious disease testing rates (hepatitis B and C viruses, human immunodeficiency virus, and tuberculosis) for March, April, and May in 2020 compared to the previous year. Reported deaths as a result of overdose did not increase during the state of alarm, but 2/11 (18%) centres reported an increase in overdose deaths immediately after finalisation of the state of alarm. Overall, Spanish harm reduction centres were able to continue operating and offering services by adjusting operating hours. The number of overall service users and needles distributed fell during the Spanish state of alarm lockdown period, suggesting that fewer clients accessed harm reduction services during this time, putting them at greater risk of reusing or sharing injecting equipment, overdosing, acquiring infectious diseases with decreased access to testing or discontinuing ongoing treatment such as methadone maintenance therapy, hepatitis C treatment, or antiretroviral therapy

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

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

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