ABSTRACT
Canada has recently published a new Clinical Practice Guideline on the diagnosis and management of brain death. It states that consent is not necessary to carry out the interventions required to make the diagnosis. A supporting article not only sets out the arguments for this but also contends that 'UK laws similarly carve out an exception, excusing clinicians from a prima facie duty to get consent'. This is supplemented by the claim that recent court decisions in the UK similarly confirm that consent is not required, referencing two judgements in Battersbee We disagree with the authors' interpretation of the law on consent in the UK and argue that there is nothing in Battersbee to support the conclusion that consent to testing is not necessary. Where there is a disagreement about testing for brain death in the UK, court authorisation is required.
ABSTRACT
The reality of current clinical practice in the UK is that where a patient's family refuses to agree to testing for brain stem death (BD), such cases will ultimately end up in court. This situation is true of both adults and children and reinforced by recent legal cases. While recourse to the courts might be regrettable in such tragic cases, if public trust in the medical diagnosis of BD is to be maintained all aspects of the process must be conducted in a way that is transparent and open to scrutiny. This is not an 'ineffective expenditure' of resources, but an essential element of a human rights-compliant legal system.
Subject(s)
Brain Death , Human Rights , Humans , United Kingdom , Brain Death/legislation & jurisprudence , Brain Death/diagnosis , Human Rights/legislation & jurisprudence , Adult , Brain Injuries , ChildABSTRACT
Through a series of x-ray diffraction, optical spectroscopy diamond anvil cell experiments, combined with density functional theory calculations, we explore the dense CH_{4}-H_{2} system. We find that pressures as low as 4.8 GPa can stabilize CH_{4}(H_{2})_{2} and (CH_{4})_{2}H_{2}, with the latter exhibiting extreme hardening of the intramolecular vibrational mode of H_{2} units within the structure. On further compression, a unique structural composition, (CH_{4})_{3}(H_{2})_{25}, emerges. This novel structure holds a vast amount of molecular hydrogen and represents the first compound to surpass 50 wt % H_{2}. These compounds, stabilized by nuclear quantum effects, persist over a broad pressure regime, exceeding 160 GPa.
ABSTRACT
Human jumping translocation breakpoint (hJTB) gene is located on chromosome 1q21 and is involved in unbalanced translocation in many types of cancer. JTB protein is ubiquitously present in normal cells but it is found to be overexpressed or downregulated in various types of cancer cells, where this protein and its isoforms promote mitochondrial dysfunction, resistance to apoptosis, genomic instability, proliferation, invasion and metastasis. Hence, JTB could be a tumor biomarker for different types of cancer, such as breast cancer (BC), and could be used as a drug target for therapy. However, the functions of the protein or the pathways through which it increases cell proliferation and invasiveness of cancer cells are not well-known. Therefore, we aim to investigate the functions of JTB by using in-solution digestion-based cellular proteomics of control and upregulated and downregulated JTB protein in MCF7 breast cancer cell line, taking account that in-solution digestion-based proteomics experiments are complementary to the initial in-gel based ones. Proteomics analysis allows investigation of protein dysregulation patterns that indicate the function of the protein and its interacting partners, as well as the pathways and biological processes through which it functions. We concluded that JTB dysregulation increases the epithelial-mesenchymal transition (EMT) potential and cell proliferation, harnessing cytoskeleton organization, apical junctional complex, metabolic reprogramming, and cellular proteostasis. Deregulated JTB expression was found to be associated with several proteins involved in mitochondrial organization and function, oxidative stress (OS), apoptosis, and interferon alpha and gamma signaling. Consistent and complementary to our previous results emerged by using in-gel based proteomics of transfected MCF7 cells, JTB-related proteins that are overexpressed in this experiment suggest the development of a more aggressive phenotype and behavior for this luminal type A non-invasive/poor-invasive human BC cell line that does not usually migrate or invade compared with the highly metastatic MDA-MB-231 cells. This more aggressive phenotype of MCF7 cells related to JTB dysregulation and detected by both in-gel and in-solution proteomics could be promoted by synergistic upregulation of EMT, Mitotic spindle and Fatty acid metabolism pathways. However, in both JTB dysregulated conditions, several downregulated JTB-interacting proteins predominantly sustain antitumor activities, attenuating some of the aggressive phenotypical and behavioral traits promoted by the overexpressed JTB-related partners.
Subject(s)
Breast Neoplasms , Proteomics , Humans , Female , MCF-7 Cells , Proteomics/methods , Epithelial-Mesenchymal Transition/genetics , Apoptosis/genetics , Cell Proliferation , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/genetics , Neoplasm InvasivenessABSTRACT
Mass Spectrometry (MS) allows the analysis of proteins and peptides through a variety of methods, such as Electrospray Ionization-Mass Spectrometry (ESI-MS) or Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS). These methods allow identification of the mass of a protein or a peptide as intact molecules or the identification of a protein through peptide-mass fingerprinting generated upon enzymatic digestion. Tandem mass spectrometry (MS/MS) allows the fragmentation of proteins and peptides to determine the amino acid sequence of proteins (top-down and middle-down proteomics) and peptides (bottom-up proteomics). Furthermore, tandem mass spectrometry also allows the identification of post-translational modifications (PTMs) of proteins and peptides. Here, we discuss the application of MS/MS in biomedical research, indicating specific examples for the identification of proteins or peptides and their PTMs as relevant biomarkers for diagnostic and therapy.
Subject(s)
Biomedical Research , Tandem Mass Spectrometry , Amino Acid Sequence , Peptide Mapping/methods , Peptides/chemistry , Proteins/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
Ireland has been a leader in the COVID-19 vaccine rollout in the EU, with almost 80% of the eligible population (aged over 5 years) fully vaccinated at the time of writing. The success of the vaccine rollout in this jurisdiction notwithstanding, the legal frameworks supporting the rollout had significant lacunas. Two aspects in particular highlighted a lack of legal preparedness: the inadequacy of the legal framework for consent and the absence of a vaccine injury redress scheme. This paper explores these components of the COVID-19 vaccine rollout through the lens of legal preparedness. Whilst most often discussed in the context of command and control measures such as social distancing requirements and regional lockdowns, this paper argues for an expanded understanding of what it means to be legally prepared, highlighting the importance of the preparedness of domestic legal frameworks.
Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Humans , Ireland , SARS-CoV-2 , VaccinationABSTRACT
Mixtures of ammonia and water are major components of the "hot ice" mantle regions of icy planets. The ammonia-rich ammonia hemihydrate (AHH) plays a pivotal role as it precipitates from water-rich mixtures under pressure. It has been predicted to form ionic high-pressure structures, with fully disintegrated water molecules. Utilizing Raman spectroscopy measurements up to 123 GPa and first-principles calculations, we report the spontaneous ionization of AHH under compression. Spectroscopic measurements reveal that molecular AHH begins to transform into an ionic state at 26 GPa and then above â¼69 GPa transforms into the fully ionic P3[over ¯]m1 phase, AHH-III, characterized as ammonium oxide (NH_{4}^{+})_{2}O^{2-}.
Subject(s)
Informed Consent , Referral and Consultation , Humans , United States , United Kingdom , Informed Consent/ethicsABSTRACT
OBJECTIVE: V565 is a novel oral anti-tumor necrosis factor (TNF)-α domain antibody being developed for topical treatment of inflammatory bowel disease (IBD) patients. Protein engineering rendered the molecule resistant to intestinal proteases. Here we investigate the formulation of V565 required to provide gastro-protection and enable optimal delivery to the lower intestinal tract in monkeys. METHODS: Enteric-coated V565 mini-tablets were prepared and dissolution characteristics tested in vitro. Oral dosing of monkeys with enteric-coated mini-tablets containing V565 and methylene blue dye enabled in vivo localization of mini-tablet dissolution. V565 distribution in luminal contents and feces was measured by enzyme-linked immunosorbent assay (ELISA). To mimic transit across the damaged intestinal epithelium seen in IBD patients an intravenous (i.v.) bolus of V565 was given to monkeys and pharmacokinetic parameters of V565 measured in serum and urine by ELISA. RESULTS: Enteric-coated mini-tablets resisted dissolution in 0.1 M HCl, before dissolving in a sustained release fashion at neutral pH. In orally dosed monkeys methylene blue intestinal staining indicated the jejunum and ileum as sites for mini-tablet dissolution. Measurements of V565 in monkey feces confirmed V565 survival through the intestinal tract. Systemic exposure after oral dosing was very low consistent with limited V565 mucosal penetration in healthy monkeys. The rapid clearance of V565 after i.v. dosing was consistent with renal excretion as the primary route for elimination of any V565 reaching the circulation. CONCLUSIONS: These results suggest that mini-tablets with a 24% Eudragit enteric coating are suitable for targeted release of orally delivered V565 in the intestine for topical treatment of IBD.
Subject(s)
Antibodies/administration & dosage , Antineoplastic Agents/administration & dosage , Ileum/drug effects , Inflammatory Bowel Diseases/economics , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Administration, Oral , Animals , Antibodies/metabolism , Antineoplastic Agents/pharmacokinetics , Chemistry, Pharmaceutical/methods , Feces , Hydrogen-Ion Concentration , Ileum/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Jejunum/drug effects , Jejunum/metabolism , Macaca fascicularis , Solubility , Tablets, Enteric-Coated/administration & dosage , Tablets, Enteric-Coated/pharmacokineticsABSTRACT
This article analyses the balance which the GDPR strikes between two important social values: protecting personal health data and facilitating health research through the lens of the consent requirement and the research exemption. The article shows that the normative weight of the consent requirement differs depending on the context for the health research in question. This more substantive approach to consent is reflected in the research exemption which allows for a more nuanced balancing of interests. However, because the GDPR articulates the exemption at an abstract and principled level, in practice the balance is struck at Member State level. Thus, the GDPR increases difficulties for EU cross-border health projects and impedes the policy goal of creating a harmonised regulatory framework for health research. The article argues that in order to address this problem, the European Data Protection Board should provide specific guidance on the operation of consent in health research.
Subject(s)
Biomedical Research/legislation & jurisprudence , Computer Security/legislation & jurisprudence , Data Anonymization/legislation & jurisprudence , Health Records, Personal , Informed Consent/legislation & jurisprudence , European Union , Humans , ProxyABSTRACT
Through a series of Raman spectroscopy studies, we investigate the behavior of hydrogen-helium and hydrogen-nitrogen mixtures at high pressure across a wide range of concentrations. We find that there is no evidence of chemical association or increased miscibility of hydrogen and helium in the solid state up to pressures of 250 GPa at 300 K. In contrast, we observe the formation of concentration-dependent N_{2}-H_{2} van der Waals solids, which react to form N-H bonded compounds above 50 GPa. Through this combined study, we can demonstrate that the recently reported chemical association of H_{2}-He can be attributed to significant N_{2} contamination and subsequent formation of N_{2}-H_{2} compounds.
ABSTRACT
In situ high-pressure high-temperature X-ray powder diffraction studies of the cobalt-hydrogen system reveal the direct synthesis of both the binary cobalt hydride (CoH) and a novel cobalt dihydride (CoH2). We observe the formation of fcc CoH at pressures of 4 GPa, which persists to pressures of 45 GPa. At this pressure, we see the emergence with time of a further expanded fcc lattice, which we identify as CoH2, where the hydrogen atoms occupy the tetrahedral vacancies. We have explored alternative synthesis routes of CoH2 and can lower the synthesis pressure to 35 GPa by the application of high temperature. CoH2 is stable to at least 55 GPa and decomposes into CoH below 10 GPa, releasing molecular hydrogen before further decomposing completely into its constituent elements below 3 GPa. As a first-row transition metal, cobalt has a relatively lower mass than other hydride-forming transition metals, and as a result, CoH2 has a high hydrogen content of 3.3 wt. % and a volumetric hydrogen density of 214 g/l.
ABSTRACT
THIS case commentary analyses the application of the best interests standard in section 4 of the Mental Capacity Act 2005 by the Court in the decision in Abertawe Bro Morgannwg University Local Health Board v RY (by his litigation friend the official solicitor) and CP [2017] EWCOP 2. It evaluates the way in which the law impacted on how clinical decisions in respect of RY were made and identifies systemic concerns arising from the case.
Subject(s)
Clinical Decision-Making , Persistent Vegetative State , Withholding Treatment/legislation & jurisprudence , Humans , Tracheostomy , United Kingdom , Withholding Treatment/ethicsABSTRACT
Background Undergraduate nursing education standards include acquisition of knowledge of ethics principles and the prevalence of health-care ethical dilemmas mandates that nursing students study ethics. However, little research has been published to support best practices for teaching/learning ethics principles. Purpose This study sought to determine if participation in an ethics consultation simulation increased nursing students' knowledge of nursing ethics principles compared to students who were taught ethics principles in the traditional didactic format. Methods This quasi-experimental study utilized a pre-test/post-test design with randomized assignment of students at three universities into both control and experimental groups. Results Nursing students' knowledge of nursing ethics principles significantly improved from pre-test to post-test ( p = .002); however, there was no significant difference between the experimental and control groups knowledge scores ( p = .13). Conclusion Further research into use of simulation to teach ethics principles is indicated.
Subject(s)
Education, Nursing, Baccalaureate/methods , Educational Measurement/statistics & numerical data , Ethics, Nursing/education , Simulation Training , Students, Nursing/psychology , Humans , Nursing Education Research , Nursing Evaluation Research , Nursing Methodology ResearchABSTRACT
This article examines the legislative frameworks for advance healthcare planning in England & Wales (the Mental Capacity Act 2005) and in Ireland (the Assisted Decision-Making (Capacity) Act 2015), undertaking a comparative analysis of each measure, with particular focus on the detail of the approaches taken. It is only through this kind of detailed focus that the normative choices made by legislation can fully be understood and evaluated. The article argues that, in several respects, possibly because the drafters were able to reflect lessons learned from other jurisdictions, the Assisted Decision-Making (Capacity) Act 2015 provides a more rounded and complete form of advance healthcare planning than that provided by the Mental Capacity Act. This is on the basis that it provides more protection for patient choice; better potential for delivery on the choices made; and a more appropriate balance between formalities and enforceability.
Subject(s)
Advance Care Planning/legislation & jurisprudence , England , Humans , Ireland , Mental Competency/legislation & jurisprudence , WalesABSTRACT
Article 12 of the United Nations Convention on the Rights of Persons with Disabilities, as interpreted by the Committee on the Rights of Persons with Disabilities in General Comment No. 1, offers a vision for law's response to capacity impairments which differs in crucial ways from that contained in the Mental Capacity Act 2005. The Committee rejects the functional test for capacity and requires that a 'will and preferences' paradigm must replace the 'best interests' paradigm and that all substitute decision-making regimes must be abolished. This article draws on the position adopted in General Comment No. 1 in evaluating the best interests standard in the Mental Capacity Act. It sets out the normative case for a stronger legislative endorsement of will and preferences and the inclusion of greater support mechanisms but rejects the contention that all substitute decision-making can, or should, be abolished. It also argues that the best interests standard in the Mental Capacity Act retains some revolutionary potential and that, pending legislative reform, this can be further developed through the courts.
Subject(s)
Decision Making , Disabled Persons , Mental Competency , Humans , United NationsABSTRACT
In this paper we examine the role of informed consent to capacity assessment, focussing primarily on the two jurisdictions of England and Wales, and Ireland. We argue that in both jurisdictions, a capacity assessment should be regarded as a distinct intervention, separate from the 'original' intervention at issue, and that specific informed consent to the assessment should generally be sought in advance. As part of this, we consider what information should be provided so as to ensure informed consent. Having established a baseline requirement for informed consent, we also recognise that informed consent to assessment will not always be possible, either because the person is unable to understand the information about assessment or because the person refuses to be assessed and so, in the final part of the article, we explore how to proceed when informed consent is either not possible or not forthcoming, including an analysis of the implications of the statutory presumption of capacity.
Subject(s)
Informed Consent , Mental Competency , Humans , England , Wales , Ireland , Decision MakingABSTRACT
The island of Ireland is partitioned into Northern Ireland and the Republic of Ireland. In both jurisdictions, there have been important developments in mental health and mental capacity law, and associated policies and services. This includes an emphasis on developing more comprehensive approaches to collecting data on outcomes and so there is an opportunity to align these processes to enable comparison and shared learning across the border. This article explores: legal and policy developments; international approaches to mental health outcomes; and the type of data that would be helpful to collect to better understand the use of mental health and mental capacity laws. It is argued that an inclusive strategy to developing a comprehensive, integrated and aligned approach to collecting and analysing data would benefit citizens, policy makers and professionals.