Effect of expectoration on inflammation in induced sputum in α-1-antitrypsin deficiency

SummaryIt is unclear how chronic expectoration influences airway inflammation in patients with chronic lung disease. The aim of this study was to investigate factors influencing inflammation in induced sputum samples, including, in particular, chronic sputum production. Myeloperoxidase, interleukin-8, leukotriene B4 (LTB4), neutrophil elastase, secretory leukoprotease inhibitor (SLPI) and protein leakage were compared in induced sputum samples from 48 patients (36 with chronic expectoration) with COPD (with and without alpha-1-antitrypsin deficiency; AATD), 9 individuals with AATD but without lung disease and 14 healthy controls. There were no differences in inflammation in induced sputum samples from healthy control subjects and from AATD deficient patients with normal lung function but without chronic expectoration (P>0.05). Inflammation in induced sputum from AATD patients with airflow obstruction and chronic sputum expectoration was significantly greater than for similar patients who did not expectorate: Interleukin-8 (P<0.01), elastase activity (P=0.01), and protein leakage (P<0.01). The presence of spontaneous sputum expectoration in AATD patients with airflow obstruction was associated with increased neutrophilic airway inflammation in induced sputum samples. The presence of chronic expectoration in some patients will clearly complicate interpretation of studies employing sputum induction where this feature has not been identified

Imaging fictive locomotor patterns in larval Drosophila.

We have established a preparation in larval Drosophila to monitor fictive locomotion simultaneously across abdominal and thoracic segments of the isolated CNS with genetically encoded Ca(2+) indicators. The Ca(2+) signals closely followed spiking activity measured electrophysiologically in nerve roots. Three motor patterns are analyzed. Two comprise waves of Ca(2+) signals that progress along the longitudinal body axis in a posterior-to-anterior or anterior-to-posterior direction. These waves had statistically indistinguishable intersegmental phase delays compared with segmental contractions during forward and backward crawling behavior, despite being ∼10 times slower. During these waves, motor neurons of the dorsal longitudinal and transverse muscles were active in the same order as the muscle groups are recruited during crawling behavior. A third fictive motor pattern exhibits a left-right asymmetry across segments and bears similarities with turning behavior in intact larvae, occurring equally frequently and involving asymmetry in the same segments. Ablation of the segments in which forward and backward waves of Ca(2+) signals were normally initiated did not eliminate production of Ca(2+) waves. When the brain and subesophageal ganglion (SOG) were removed, the remaining ganglia retained the ability to produce both forward and backward waves of motor activity, although the speed and frequency of waves changed. Bilateral asymmetry of activity was reduced when the brain was removed and abolished when the SOG was removed. This work paves the way to studying the neural and genetic underpinnings of segmentally coordinated motor pattern generation in Drosophila with imaging techniques.S.R.P. was supported by a Newton International Fellowship (Royal Society) and a Junior Fellowship (Janelia Research Campus, Howard Hughes Medical Institute). T.G.B. was supported by a Medical Research Council (UK) PhD grant. J.B. was supported by a Henry Dale Fellowship (Royal Society and Wellcome Trust). M.B. was supported by the Isaac Newton Trust.This is the final version of the article. It first appeared from the American Physiological Society via http://dx.doi.org/10.1152/jn.00731.201

Privacy Impact Assessments: international experience as a basis for UK guidance

In July 2007, the UK Information Commissioner’s Office commissioned a team of researchers, coordinated by Loughborough University, to conduct a study into Privacy Impact Assessments (PIAs). This was with a view to developing PIA guidance for the UK. The project resulted in two key deliverables: a study of the use of PIAs in other jurisdictions, identifying lessons to be learnt for the UK; and a handbook that can be used to guide organisations through the PIA process, taking into account the provisions of the UK Data Protection Act (DPA) 1998. This paper draws on the original research undertaken as part of that assignment to provide an overview of the ICO-funded project and the extent to which PIAs can be used in the current UK context. Firstly, the authors consider the findings of the comparative study and how the UK experience can be informed by developments overseas. Secondly, the paper outlines the development of the handbook during the course of the project and the extent to which it has been influenced by the overseas experience and the current UK political context. Thirdly, aspects of the handbook itself are considered and explained. Particular attention is paid to: its format; its key features; and feedback received on an interim version from a focus group of experienced data protection and project management practitioners. Finally, the paper concludes by stating why the study and the handbook provide appropriate tools for guidance in the current UK context, and how they can be developed further

Privacy Impact Assessments: the UK experience

This paper builds on original work undertaken as part of a team of researchers into Privacy Impact Assessments (PIAs), defined as a systematic risk assessment tool that can be usefully integrated into decision-making processes. The team were commissioned by the UK Information Commissioner’s Office (ICO) in June 2007 to develop a study of PIAs in overseas jurisdictions and a handbook to guide UK organisations through the PIA process. This research has subsequently attracted interest in the UK and overseas. PIAs are now mandatory for all UK central government departments. In this paper, the development of the project team’s PIA methodology and subsequent user experiences led to a key project output, the PIA handbook. The handbook has become a significant part of the privacy ‘toolkit’ and has impacted on public policy. Some important lessons from PIAs conducted in the UK and overseas are identified. Finally, areas are outlined for further development

Extending the concept of research impact literacy: levels of literacy, institutional role and ethical considerations

Building on the concept of ‘impact literacy’ established in a previous paper from Bayley and Phipps, here we extend the principles of impact literacy in light of further insights into sector practice. More specifically, we focus on three additions needed in response to the sector-wide growth of impact: (1) differential levels of impact literacy; (2) institutional impact literacy and environment for impact; and (3) issues of ethics and values in research impact. This paper invites the sector to consider the relevance of all dimensions in establishing, maintaining and strengthening impact within the research landscape. We explore implications for individual professional development, institutional capacity building and ethical collaboration to maximise societal benefit

“Starting to think that way from the start”: approaching deprescribing decision-making for people accessing palliative care - a qualitative exploration of healthcare professionals views

BackgroundDeprescribing has been defined as the planned process of reducing or stopping medications that may no longer be beneficial or are causing harm, with the goal of reducing medication burden while improving patient quality of life. At present, little is known about the specific challenges of decision-making to support deprescribing for patients who are accessing palliative care. By exploring the perspectives of healthcare professionals, this qualitative study aimed to address this gap, and explore the challenges of, and potential solutions to, making decisions about deprescribing in a palliative care context.MethodsSemi-structured interviews were conducted with healthcare professionals in-person or via video call, between August 2022 – January 2023. Perspectives on approaches to deprescribing in palliative care; when and how they might deprescribe; and the role of carers and family members within this process were discussed. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the NHS Health Research Authority (ref 305394).ResultsTwenty healthcare professionals were interviewed, including: medical consultants, nurses, specialist pharmacists, and general practitioners (GPs). Participants described the importance of deprescribing decision-making, and that it should be a considered, proactive, and planned process. Three themes were developed from the data, which centred on: (1) professional attitudes, competency and responsibility towards deprescribing; (2) changing the culture of deprescribing; and (3) involving the patient and family/caregivers in deprescribing decision-making.ConclusionsThis study sought to explore the perspectives of healthcare professionals with responsibility for making deprescribing decisions with people accessing palliative care services. A range of healthcare professionals identified the importance of supporting decision-making in deprescribing, so it becomes a proactive process within a patient’s care journey, rather than a reactive consequence. Future work should explore how healthcare professionals, patients and their family can be supported in the shared decision-making processes of deprescribing

High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing

AbstractBioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (107 cells mL−1) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.</jats:p

Privacy Impact Assessments: International Experience as a Basis for UK Guidance

This article was subsequently published in the journal Computer Law & Security Report [Elsevier / © The authors]. The definitive version is available at: http://www.sciencedirect.com/science/journal/02673649. Whilst this paper was submitted in response to referee comments, it may not exactly match the final published versions.In July 2007, the UK Information Commissioner’s Office commissioned a team of researchers, coordinated by Loughborough University, to conduct a study into Privacy Impact Assessments (PIAs). This was with a view to developing PIA guidance for the UK. The project resulted in two key deliverables: a study of the use of PIAs in other jurisdictions, identifying lessons to be learnt for the UK; and a handbook that can be used to guide organisations through the PIA process, taking into account the provisions of the UK Data Protection Act (DPA) 1998. This paper draws on the original research undertaken as part of that assignment to provide an overview of the ICO-funded project and the extent to which PIAs can be used in the current UK context. Firstly, the authors consider the findings of the comparative study and how the UK experience can be informed by developments overseas. Secondly, the paper outlines the development of the handbook during the course of the project and the extent to which it has been influenced by the overseas experience and the current UK political context. Thirdly, aspects of the handbook itself are considered and explained. Particular attention is paid to: its format; its key features; and feedback received on an interim version from a focus group of experienced data protection and project management practitioners. Finally, the paper concludes by stating why the study and the handbook provide appropriate tools for guidance in the current UK context, and how they can be developed further

A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

SummaryThe identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH), predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target

Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust

Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. We developed an in-house ELISA for testing participant serum for SARS-CoV-2 IgG and IgA reactivity against Spike and Nucleoprotein. Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: Our in-house assay had a sensitivity of 99·47% and specificity of 99·56%. We found that 24·4% (n=311/1275) of HCWs were seropositive as of 12th June 2020. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0–52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4–56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. Conclusions: HCWs in acute medical units and those working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more severe COVID-19 cases