Impact of cytological sampling on EGFR mutation testing in stage III-IV lung adenocarcinoma

Objectives. There have been advances in the identification and understanding of molecular subsets of lung cancer, defined by specific oncogenic aberrations. A number of actionable genetic alterations have been identified, such as the epidermal growth factor receptor (EGFR) mutation. We aimed to establish the reasons why patients were not undergoing EGFR mutation testing at the time of histological diagnosis. Methods. The records of 70 patients with advanced adenocarcinoma of the lung managed through a single multidisciplinary team at a single institution were reviewed. Data were collected on method of tumour sample collection, whether this was sent for EGFR testing, and the result. Results. Seventy patients were identified. In 21/25 (84%) cases, cytological sampling was sufficient for EGFR mutation analysis, compared with 40/45 (89%) cases with histological sampling. EGFR mutation testing was not carried out in 22/70 (31.4%) patients. There was insufficient tumour sample for EGFR testing in 9/22 (40.9%) patients. Other reasons for not testing included poor patient fitness and problems in the diagnostic pathway. Conclusions. In this series, cytological tumour sampling was not the predominant reason why cancers failed to have EGFR mutation status established

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Genome-wide association meta-analysis of age at onset of walking in over 70,000 infants of European ancestry

Age at onset of walking is an important early childhood milestone which is used clinically and in public health screening. In this genome-wide association study meta-analysis of age at onset of walking (N = 70,560 European-ancestry infants), we identified 11 independent genome-wide significant loci. SNP-based heritability was 24.13% (95% confidence intervals = 21.86–26.40) with ~11,900 variants accounting for about 90% of it, suggesting high polygenicity. One of these loci, in gene RBL2, co-localized with an expression quantitative trait locus (eQTL) in the brain. Age at onset of walking (in months) was negatively genetically correlated with ADHD and body-mass index, and positively genetically correlated with brain gyrification in both infant and adult brains. The polygenic score showed out-of-sample prediction of 3–5.6%, confirmed as largely due to direct effects in sib-pair analyses, and was separately associated with volume of neonatal brain structures involved in motor control. This study offers biological insights into a key behavioural marker of neurodevelopment

Memory, the Transition and the Transnational in Iberia. (Eds.) Susana Relvas, Mark Gant, Siân Edwards. Cambridge Scholars Publishing.

This volume brings together a wide range of innovative research across the diverse field of Iberian Studies. It will be of interest to academic staff and research students, and will also provide a resource for undergraduate projects and for all those wishing to deepen their knowledge of the Iberian countries and their relationships with other parts of the world. The collection includes cutting-edge work in the fields of memory politics and historical revisionism, peninsular dictatorships, the Spanish Civil War, the Francoist legacy and transition to democracy, and colonial and postcolonial transnational exchanges between Iberia and other continents on a global scale. Within these core themes, pressing topics such as migrations, resistance, memory, exile and trauma, violence, sexuality and feminism, and their literary and artistic representations form the core of the volume. The 16 chapters are written by established and early career researchers from Brazil, India, Ireland, Hungary, Portugal, Spain, the UK, and the USA.info:eu-repo/semantics/publishedVersio

Preface

The Iberian Peninsula, home to modern-day Spain and Portugal, serves as a crossroads of regional, international, and transatlantic relations. The peninsula plays a pivotal role in shaping global interactions through its cultural exchanges and geopolitical alliances. This continues to influence global politics, economics, and cultural identity, making the study of Iberia’s relationships crucial to understanding global trends. By examining its connections across Europe, Africa, the Americas, and beyond, researchers may gain insight into how the Iberian Peninsula shapes and is shaped by the world. Regional, International, and Transatlantic Relations From the Iberian Peninsula to the World explores memory politics and historical revisionism, focusing on dictatorships, migrations and exiles, as well as cross border dialogues between communities within the Iberian Peninsula. It examines international relations, centering on the Anglo-Iberian contacts and influences in the political, historical and cultural domains, and on transatlantic studies in North and South America. This book covers topics such as diplomacy, regional development, and nationalism, and is a useful resource for business owners, historians, government officials, policymakers, academicians, researchers, and scientists

Towards ethical international research partnerships in gender-based violence research:insights from research partners in Kenya

Research with survivors of gender-based violence in low- and middle-income countries is important to improve understanding of experiences of violence and the policies that can help combat it. But this research also implies risks for survivors, such as re-traumatization, safety concerns, and feelings of exploitation. These risks are magnified if research is undertaken by researchers from high-income countries, whose positionality produces power inequalities affecting both participants and research partners. This article describes the ethical challenges of international gender-based violence research from the perspective of Kenyan researchers and organizations and identifies recommendations about how to prevent them

Towards Ethical International Research Partnerships in Gender-Based Violence Research: Insights From Research Partners in Kenya

Research with survivors of gender-based violence in low- and middle-income countries is important to improve understanding of experiences of violence and the policies that can help combat it. But this research also implies risks for survivors, such as re-traumatization, safety concerns, and feelings of exploitation. These risks are magnified if research is undertaken by researchers from high-income countries, whose positionality produces power inequalities affecting both participants and research partners. This article describes the ethical challenges of international gender-based violence research from the perspective of Kenyan researchers and organizations and identifies recommendations about how to prevent them. </jats:p

Voriconazole therapy in children with cystic fibrosis

AbstractBackgroundThere is increasing evidence for the efficacy of the antifungal voriconazole, particularly in immunosuppression. We describe our experience of using voriconazole in children with CF.MethodsWe performed a retrospective case note review of children with CF treated with voriconazole in a single centre over an 18 month period.ResultsA total of 21 children aged 5 to 16 years (median 11.3) received voriconazole for between 1 and 50 (22) weeks. Voriconazole was used as monotherapy in 2 children with recurrent allergic bronchopulmonary aspergillosis (ABPA); significant and sustained improvements in clinical and serological parameters for up to 13 months were observed, without recourse to oral steroids. Voriconazole was used in combination with an immunomodulatory agent in a further 11 children with ABPA, with significant improvement in pulmonary function and serology. 8 children without ABPA but who had recurrent Aspergillus fumigatus isolates and increased symptoms also received voriconazole; this group did not improve with treatment. Adverse effects occurred in 7 children (33%: photosensitivity reaction 3, nausea 2, rise in hepatic enzymes 1, hair loss 1).ConclusionsVoriconazole may be a useful adjunctive therapy for ABPA in CF. Voriconazole monotherapy appears to be an alternative treatment strategy when oral corticosteroids may not be suitable