Single-arm, first-in-human feasibility study results for an ultra-low-cost insulin pump.

Background: Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices.

Analysis of "Hybrid Closed Loop Using a Do-It-Yourself Artificial Pancreas System in Adults With Type 1 Diabetes".

In an article in , Nanayakkara and colleagues assessed the glycemic efficacy and safety of AndroidAPS, an open-source automated delivery (AID) system, in a crossover randomized controlled trial. Although the trial included only 20 participants during a relatively short 4-week intervention period, glycemic outcomes attained were similar to commercial AID systems and there were no safety concerns. Validation of open-source AID systems in studies such as this should help address clinician hesitancy regarding these systems, and affirms the role of patient-centered innovation and self-management in diabetes care.

Wave comparisons of clinical characteristics and outcomes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics.

Objectives: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study.

The preferences of patients with chronic obstructive pulmonary disease are to discuss palliative care plans with familiar respiratory clinicians, but to delay conversations until their condition deteriorates: A study guided by interpretative phenomenological analysis.

Background: Chronic obstructive pulmonary disease is associated with an uncertain trajectory, which challenges prognostication and means that most patients are not involved in advance care planning and do not receive palliative and end-of-life care.

Aim: To understand the preferences of patients with chronic obstructive pulmonary disease for discussions about palliative and advance care planning with clinicians.

Design: Semi-structured interviews were conducted with patients with chronic obstructive pulmonary disease.

Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes.

Background: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2.

Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: a population database study using linked health care records.

Background: Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity. However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.

Methods: A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.

Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD.

Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.

Human Lung Fibroblasts Present Bacterial Antigens to Autologous Lung Th Cells.

Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4 Th cells. During severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating Th cell responses to NTHi.

Selection into medical school: from tools to domains.

Background: Most research into the validity of admissions tools focuses on the isolated correlations of individual tools with later outcomes. Instead, looking at how domains of attributes, rather than tools, predict later success is likely to be more generalizable. We aim to produce a blueprint for an admissions scheme that is broadly relevant across institutions.

Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function.

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases.

Background: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown.

Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units).

Present and future utility of computed tomography scanning in the assessment and management of COPD.

Computed tomography (CT) is the modality of choice for imaging the thorax and lung structure. In chronic obstructive pulmonary disease (COPD), it used to recognise the key morphological features of emphysema, bronchial wall thickening and gas trapping. Despite this, its place in the investigation and management of COPD is yet to be determined, and it is not routinely recommended.

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection.

Rationale: Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive pulmonary disease (COPD) exacerbations and is a plausible target for MAIT cells.

Objectives: To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids (ICS) on their frequency and function in COPD.

Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD.

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.

Objectives: We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls.

Dysregulation of Antiviral Function of CD8(+) T Cells in the Chronic Obstructive Pulmonary Disease Lung. Role of the PD-1-PD-L1 Axis.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory viral infections that cause exacerbations. The mechanisms underlying this susceptibility are not understood. Effectors of the adaptive immune response-CD8(+) T cells that clear viral infections-are present in increased numbers in the lungs of patients with COPD, but they fail to protect against infection and may contribute to the immunopathology of the disease.

A novel lung explant model for the ex vivo study of efficacy and mechanisms of anti-influenza drugs.

Influenza A virus causes considerable morbidity and mortality largely because of a lack of effective antiviral drugs. Viral neuraminidase inhibitors, which inhibit viral release from the infected cell, are currently the only approved drugs for influenza, but have recently been shown to be less effective than previously thought. Growing resistance to therapies that target viral proteins has led to increased urgency in the search for novel anti-influenza compounds.

Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection.

Recurrence of high-grade cervical abnormalities following conservative management of cervical intraepithelial neoplasia grade 2.

Objective: Conservative management of cervical intraepithelial neoplasia (CIN) grade 2 in women younger than 25 years may reduce overtreatment. However, long-term efficacy remains uncertain. This retrospective cohort study aimed to determine the rate of recurrence of high-grade abnormalities among young women with a history of CIN 2 that spontaneously regressed within 2 years and compare this with the rate of high-grade abnormality in similar women with an initial diagnosis of CIN 1.

Preparation courses for a medical admissions test: effectiveness contrasts with opinion.

Objectives: The Undergraduate Medicine and Health Sciences Admissions Test (UMAT) is used to rank applicants for admission to many medical schools. This study aimed to determine the effects of preparation courses on UMAT performance and on students' perceptions of their performance.

Methods: We asked students who sat the UMAT twice across two consecutive years to complete an online survey.

Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans.

Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection.

Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations.

Rationale: Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations.

Objectives: To determine whether regular therapy with macrolides reduces exacerbation frequency.