Publications by authors named "Costello A"

Unlabelled: Policy Points A redirection of measurement in health care from a narrow focus on diseases and care processes towards assessing whole person health, as perceived by the person themself, may provide a galvanizing view of how health care can best meet the needs of people and help patients feel heard, seen, and understood by their care team. This review identifies key tensions to navigate as well as four overarching categories of whole person health for consideration in developing an instrument optimized for clinical practice. The categories (body and mind, relationships, living environment and finances, and engagement in daily life) include nine constituent domains.

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The World Health Organization declared COVID-19 to be a public health emergency of international concern on 30 January 2020 and then a pandemic on 11 March 2020. In early 2020, a group of UK scientists volunteered to provide the public with up-to-date and transparent scientific information. The group formed the Independent Scientific Advisory Group for Emergencies (Independent SAGE) and provided live weekly briefings to the public via YouTube.

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Background: Immunotherapy has demonstrated limited activity in prostate cancer to date. This likely reflects an immune suppressive tumor microenvironment (TME), with previous studies suggesting low PD-L1 expression and a sparse immune cell infiltrate. We aimed to further characterise the immune TME in primary prostate cancer and correlate immune subset densities with clinical outcomes.

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Article Synopsis
  • The world is nearing the critical threshold of 1.5°C warming, with 2023 recording an average temperature rise of 1.45°C since pre-industrial times, leading to severe climate-related impacts.
  • The Countdown collaboration, formed to assess the health impacts of climate change post-Paris Agreement, involves over 300 experts analyzing data and trends annually.
  • The 2024 report highlights troubling increases in climate-related health risks, such as a staggering 167% rise in heat-related deaths among seniors, indicating worsening conditions affecting wellbeing globally.
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The genetic code is the foundation for all life. With few exceptions, the translation of nucleic acid messages into proteins follows conserved rules, which are defined by codons that specify each of the 20 proteinogenic amino acids. For decades, leading research groups have developed a catalogue of innovative approaches to extend nature's amino acid repertoire to include one or more noncanonical building blocks in a single protein.

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MicroRNAs (miRNAs) are small, noncoding RNAs of about 22 nucleotides in length and have proven to be useful targets for genetic modifications for desirable phenotypes in the biotech industry. The use of constitutively expressed "miRNA sponge" vectors in which multiple, tandem miRNA-binding sites containing transcripts are transcriptionally regulated by a constitutive promoter for downregulating the levels of endogenous microRNAs in Chinese hamster ovary (CHO) cells has shown to be more advantageous than using synthetic antisense oligonucleotides. The application of miRNA sponges in biotechnological processes, however, could be more effective, if the expression of miRNA sponges could be tuned.

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Background: Diagnostic excellence is central to healthcare quality and safety. Prior literature identified a lack of psychological safety and time as barriers to diagnostic reasoning education. We performed a needs assessment to inform the development of diagnostic safety education.

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Objective: The current study aims to (1) examine the association between measures of trait anger (i.e., anger temperament and anger reaction) and cardiovascular reactivity to acute psychological stress, and (2) to identify if anger expression styles moderate the association between trait anger and cardiovascular reactivity.

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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood and a disease for which we have safe and effective therapies. Early diagnosis of JIA enables timely initiation of therapy and improves long-term disease outcomes. However, many patients with JIA experience prolonged diagnostic delays and have a turbulent course to diagnosis.

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Robotic surgery has expanded internationally at pace. There are multiple local robotic training pathways but there is inconsistency in standardisation of core common components for curricula internationally. A framework is required to define key objectives that can be implemented across robotic training ecosystems.

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Supplementing translation with noncanonical amino acids (ncAAs) can yield protein sequences with new-to-nature functions but existing ncAA incorporation strategies suffer from low efficiency and context dependence. We uncover codon usage as a previously unrecognized contributor to efficient genetic code expansion using non-native codons. Relying only on conventional Escherichia coli strains with native ribosomes, we develop a plasmid-based codon compression strategy that minimizes context dependence and improves ncAA incorporation at quadruplet codons.

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We present the first case of a dupilumab-induced hyperinflammatory state in the setting of underlying eosinophilic esophagitis characterized by multisystem granulomatous inflammation. Although clinical trial data and subsequent real-world experience support dupilumab as a highly effective therapy for eosinophilic esophagitis, close monitoring for development of adverse symptoms following initiation remains paramount.

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Background: Cannabis is commonly used in the United States. However, chronic cannabis use has been linked to alterations in white matter (WM) integrity. Studies investigating WM in people who use cannabis (PWC) have produced varying results, which may be due to a variety of factors, including a focus on individual WM tracts.

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Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT.

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MicroRNAs (miRNAs) regulate approximately one-third of all human genes. The dysregulation of miRNAs has been implicated in the development of numerous human diseases, including cancers. In our investigation focusing on altering specific miRNA expression in human pancreatic cancer cells, we encountered an interesting finding.

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Background: Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30-45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae.

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Background: Young people will suffer most from climate change yet are rarely engaged in dialogue about it. Citizen science offers a method for collecting policy-relevant data, whilst promoting awareness and capacity building. We tested the feasibility and acceptability of engaging Nepalese adolescents in climate change and health-related citizen science.

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The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types.

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Introduction: Women comprise nearly 19% of the U.S. military and now serve in almost all operational roles, increasing their risk of combat trauma and injuries.

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Lymphovascular invasion, whereby tumour cells or cell clusters are identified in the lumen of lymphatic or blood vessels, is thought to be an essential step in disease dissemination. It has been established as an independent negative prognostic indicator in a range of cancers. We therefore aimed to assess the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes.

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Addressing the large carbon footprint of conferences such as the United Nations Climate Change Convention Conference of the Parties (COP) will be important for maintaining public confidence in climate policy. Transparency is also a vital aspect of creating equitable outcomes in climate policies, as those most likely to be affected or who can create change on the ground are often unable to attend in person because of the high financial costs as well as having a large carbon footprint. The selection of host locations for the regular meetings of the UN Climate Change Convention is based on a rotation amongst the five UN regions, which for 2022 was Africa.

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