Texture, twinning and metastable "tetragonal" phase in ultrathin films of HfO₂ on a Si substrate

Thin HfO<sub>2</sub> films grown on the lightly oxidised surface of (100) Si wafers have been examined using dark-field transmission electron microscopy and selected area electron diffraction in plan view. The polycrystalline film has a grain size of the order of 100 nm and many of the grains show evidence of twinning on (110) and (001) planes. Diffraction studies showed that the film had a strong [110] out-of-plane texture, and that a tiny volume fraction of a metastable (possibly tetragonal) phase was retained. The reasons for the texture, twinning and the retention of the metastable phase are discussed

Preferences of informal carers on technology packages to support meal production by people living with dementia, elicited from personalised AT and ICT product brochures

Assistive technology (AT) can help support the continued independence of people living with dementia, supported by informal carers. Opinions and preferences of informal carers towards a range of assistive and digital information and communication technologies (ICT) to support food purchase and menu selection, including navigation and online shopping, and safe meal-making by individuals living with dementia were investigated. General attitudes and experiences with assistive technologies were first probed by means of a focus group with carers (n = 6), organised through the Alzheimer’s Society in Nottingham, England. A series of AT/ICT product brochures were then produced, describing packages of technologies to enable meal production. Task-specific questions were asked of carers (n = 10) at local Memory Cafés as to the perceived capabilities of each individual for shopping and meal-making. Carers were asked to make pair-wise choices in order to select a personalised brochure and to complete a questionnaire to elicit the practicality, desirability and affordability of specific products and to probe for preferences amongst key features. Opinions on ease-of-use, aesthetics, expected safety-in-use, independence of use and stigma related to the technology packages were also collected. Results showed that carers are able to make detailed choices and express preferences about assistive and digital technologies for the individuals in their care, and customise their enabler package. Most believed that having an enabler package would improve safety. Greater exposure of carers to newer digital products would be beneficial. The brochure method could be employed on consumer websites and by AT assessors

Advanced nanoanalysis of a Hf-based high-<i>k</i> dielectric stack prior to activation

Analytical electron microscopy techniques are used to investigate elemental distributions across a high-&lt;i&gt;k&lt;/i&gt; dielectric stack with a metal gate. Electron energy-loss spectroscopy results from a Si(100)/SiO2/HfO2/TiN/a-Si gate stack confirm the presence of an oxide interfacial phase at the TiN/a-Si interface prior to activation of the stack

The Shifting Origins of International Law

Both state-centrism and Euro-centrism are under challenge in international law today and this double challenge, this work argues, is being fruitfully mirrored back into the study of the history of international law. It examines, in the first section, the effects of the rise of positivism as a method of norm-identification and the role of methodological nationalism over the study of the history of international law in the modern foundational period of international law. This is extended by an examination of how this bequeathed a double exclusionary bias regarding time and space to the study of the history of international law as well as a reiterative focus on a series of canonical events and authors to the exclusion of others such as those related to the Islamic history of international law. In the second section, the analysis turns to address why this state of historiographical affairs is changing, specifically highlighting intra-disciplinary developments within the field of the history of international law and the effects that the “international turn in the writing of history” is having on the writing of a new history of international law for a global age. The conclusion reflects on some of the tasks ahead by providing a series of historiographical signposts for the history of international law as a field of new research

My migraine voice survey. aA global study of disease burden among individuals with migraine for whom preventive treatments have failed

Background: Migraine is associated with many debilitating symptoms that affect daily functioning. My Migraine Voice is a large global cross-sectional study aimed at understanding the full burden and impact of migraine directly from patients suffering from ≥4 monthly migraine days (MMDs) with a history of prophylactic treatment failure. Methods: This study was conducted worldwide (31 countries across North and South Americas, Europe, the Middle East and Northern Africa, and the Asia-Pacific region) using an online survey administered to adults with migraine who reported ≥4 MMDs in the 3 months preceding survey administration, with pre-specified criteria of 90% having used preventive migraine treatment (80% with history of ≥1 treatment failure). Prophylactic treatment failure was defined as a reported change in preventive medication by individuals with migraine for any reason, at least once. Results: In total, 11,266 individuals participated in the survey. Seventy-four percent of the participants reported spending time in darkness/isolation due to migraine (average: 19 h/month). While 85% of all respondents reported negative aspects of living with migraine (feeling helpless, depressed, not understood), sleeping difficulties (83%), and fear of the next attack (55%), 57% shared ≥1 positive aspect (learning to cope, becoming a stronger person). Forty-nine percent reported feeling limited in daily activities throughout all migraine phases. Migraine impact on professional, private, or social domains was reported by 87% of respondents (51% in all domains). In the previous 12 months, 38% of respondents had visited the emergency department (average: 3.3 visits), whereas 23% stayed in hospital overnight (average: 3.2 nights) due to migraine. Conclusions: The burden of migraine is substantial among this cohort of individuals with at least 4 migraine days per month and for whom at least 1 preventive migraine treatment had failed. Interestingly, respondents reported some positive aspects in their migraine journey; the greater resilience and strength brought on by coping with migraine suggests that if future treatments could address existing unmet needs, these individuals with migraine will be able to maximize their contribution to society

Unexpected structures formed by the kinase RET C634R mutant extracellular domain suggest potential oncogenic mechanisms in MEN2A

The RET receptor tyrosine kinase plays a pivotal role in cell survival, proliferation, and differentiation, and its abnormal activation leads to cancers through receptor fusions or point mutations. Mutations that disrupt the disulfide network in the extracellular domain (ECD) of RET drive multiple endocrine neoplasia type 2A (MEN2A), a hereditary syndrome associated with the development of thyroid cancers. However, structural details of how specific mutations affect RET are unclear. Here, we present the first structural insights into the ECD of the RET(C634R) mutant, the most common mutation in MEN2A. Using electron microscopy, we demonstrate that the C634R mutation causes ligand-independent dimerization of the RET ECD, revealing an unusual tail-to-tail conformation that is distinct from the ligand-induced signaling dimer of WT RET. Additionally, we show that the RETC634R ECD dimer can form complexes with at least two of the canonical RET ligands and that these complexes form very different structures than WT RET ECD upon ligand binding. In conclusion, this structural analysis of cysteine-mutant RET ECD suggests a potential key mechanism of cancer induction in MEN2A, both in the absence and presence of its native ligands, and may offer new targets for therapeutic intervention.Peer reviewe