This analysis of the law's approach to healthcare decision-making critiques its liberal foundations in respect of three categories of people: adults with capacity, adults without capacity and adults ...who are subject to mental health legislation. Focusing primarily on the law in England and Wales, the analysis also draws on the law in the United States, legal positions in Australia, Canada, Ireland, New Zealand and Scotland and on the human rights protections provided by the ECHR and the Convention on the Rights of Persons with Disabilities. Having identified the limitations of a legal view of autonomy as primarily a principle of non-interference, Mary Donnelly questions the effectiveness of capacity as a gatekeeper for the right of autonomy and advocates both an increased role for human rights in developing the conceptual basis for the law and the grounding of future legal developments in a close empirical interrogation of the law in practice.
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.
Diamond and graphite are fundamental sources of carbon in the upper mantle, and their reactivity with H
-rich fluids present at these depths may represent the key to unravelling deep abiotic ...hydrocarbon formation. We demonstrate an unexpected high reactivity between carbons' most common allotropes, diamond and graphite, with hydrogen at conditions comparable with those in the Earth's upper mantle along subduction zone thermal gradients. Between 0.5-3 GPa and at temperatures as low as 300 °C, carbon reacts readily with H
yielding methane (CH
), whilst at higher temperatures (500 °C and above), additional light hydrocarbons such as ethane (C
H
) emerge. These results suggest that the interaction between deep H
-rich fluids and reduced carbon minerals may be an efficient mechanism for producing abiotic hydrocarbons at the upper mantle.
Some families have a germline risk for developing thyroid and other cancers. An understanding of the genomic alterations that occur in these tumors will help to explain the diverse clinical ...characteristics of thyroid tumors, provide diagnostic information, and direct therapy. This article reviews the classification, genetics, and risks and management of hereditary cancer syndromes, as well as the somatic gene variants found in thyroid epithelial tumors, with clinical implications.
Diatomic elemental solids are highly compressible due to the weak interactions between molecules. However, as the density increases the intra- and intermolecular distances become comparable, leading ...to a range of phenomena, such as structural transformation, molecular dissociation, amorphization, and metallisation. Here we report, following the crystallization of chlorine at 1.15(30) GPa into an ordered orthorhombic structure (oC8), the existence of a mixed-molecular structure (mC8, 130(10)-241(10) GPa) and the concomitant observation of a continuous band gap closure, indicative of a transformation into a metallic molecular form around 200(10) GPa. The onset of dissociation of chlorine is identified by the observation of the incommensurate structure (i-oF4) above 200(10) GPa, before finally adopting a monatomic form (oI2) above 256(10) GPa.
'St George's University Hospitals NHS Foundation Trust v Casey' is the latest in a growing line of cases before the UK courts concerning objections to the determination of brain stem death (BD). The ...case is distinguishable from most of the earlier jurisprudence because it concerned an adult and, in this respect, it provides helpful clarity regarding the procedural framework to be applied in such situations. However, as we will see below, in other respects the case serves to increase confusion. One particular problem that arises from the judgment in 'Casey' is how we conceptualise the legal status of an individual who has been found to be brain dead by clinicians, but this finding is disputed by families, either in respect of procedure or substance, and the courts have been asked to rule on the matter. The case also raises new questions about the operationalization of testing for BD, which questions assume particular significance given the ongoing work to revise the Academy of Medical Royal Colleges' 'Code of Practice for the Diagnosis and Confirmation of Death' (2008) (hereafter 'the Code'). This commentary will explore both of these aspects of the case. First, however, we outline the facts and identify those areas in which the legal position has been clarified.
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.
The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the ...treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L-mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment.
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.
PDF
