La boîte à outils géotechniques de demain: EN 1997-1: 202x Règles générales

This paper describes the development of the final Project Team (PT) draft of the next generation of Eurocode 7 Part 1 (EN 1997-1:202x). The use of Nationally Determined Parameters and the drive for ease-of-use is highlighted. Key changes from the previous version of EN 1997-1 are explained, including the introduction of the Geotechnical Design Model; revision of the Geotechnical Categories and their application; the implementation of Consequence Classes and Geotechnical Complexity Classes in achieving the reliability required by the Eurocodes; elaboration on the use of numerical methods within Eurocode 7; the treatment of rock on an equal basis with soil; and greater emphasis on the Observational Method.Postprint (published version

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, “poor” response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord. 20 Suppl 1:S83–91, 2005; Litvan et al. Neurology. 48:119–25, 1997; Armstrong et al. Neurology. 80(5):496–503, 2013). There is some evidence that intrasalivery gland botulinum toxin is useful in managing problematic sialorrhea and that intramuscular botulinum toxin and baclofen are helpful in reducing dystonia, including blepharospasm. Benzodiazepines may also be useful in managing dystonia. Myoclonus may be managed using levetiracetam and benzodiazepines. Pharmacological agents licensed for Alzheimer’s disease (such as acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonists) have been used off-label in PSP, CBD, and other tauopathies with the aim of improving cognition; however, there is limited evidence that they are effective and risk of adverse effects may outweigh benefits. The use of atypical antipsychotics for behavioural symptoms is not recommended in the elderly or those with demetia associated conditions and most antipsychotics will worsen Parkinsonism. Antidepressants may be useful for behavioral symptoms and depression but are often poorly tolerated due to adverse effects. In the absence of an effective drug treatment to target the underlying cause of CBD and PSP, management should focus on optimizing quality of life, relieving symptoms and assisting patients with their activities of daily living (ADL). Patients should be managed by a multidisciplinary team consisting of neurologists, physiotherapists (PT), occupational therapists (OT), speech and language therapists (SALT), dieticians, ophthalmologists, psychologists, and palliative care specialists

Spin correlations in Ca3Co2O6: A polarised-neutron diffraction and Monte Carlo study

We present polarised-neutron diffraction measurements of the Ising-like spin-chain compound Ca3Co2O6 above and below the magnetic ordering temperature TN. Below TN, a clear evolution from a single-phase spin-density wave (SDW) structure to a mixture of SDW and commensurate antiferromagnet (CAFM) structures is observed on cooling. For a rapidly-cooled sample, the majority phase at low temperature is the SDW, while if the cooling is performed sufficiently slowly, then the SDW and the CAFM structure coexist between 1.5 and 10 K. Above TN, we use Monte Carlo methods to analyse the magnetic diffuse scattering data. We show that both intra- and inter-chain correlations persist above TN, but are essentially decoupled. Intra-chain correlations resemble the ferromagnetic Ising model, while inter-chain correlations resemble the frustrated triangular-lattice antiferromagnet. Using previously-published bulk property measurements and our neutron diffraction data, we obtain values of the ferromagnetic and antiferromagnetic exchange interactions and the single-ion anisotropy.Comment: 10 pages, 7 figure

Microbicides development programme: engaging the community in the standard of care debate in a vaginal microbicide trial in Mwanza, Tanzania.

BACKGROUND: HIV prevention research in resource-limited countries is associated with a variety of ethical dilemmas. Key amongst these is the question of what constitutes an appropriate standard of health care (SoC) for participants in HIV prevention trials. This paper describes a community-focused approach to develop a locally-appropriate SoC in the context of a phase III vaginal microbicide trial in Mwanza City, northwest Tanzania. METHODS: A mobile community-based sexual and reproductive health service for women working as informal food vendors or in traditional and modern bars, restaurants, hotels and guesthouses has been established in 10 city wards. Wards were divided into geographical clusters and community representatives elected at cluster and ward level. A city-level Community Advisory Committee (CAC) with representatives from each ward has been established. Workshops and community meetings at ward and city-level have explored project-related concerns using tools adapted from participatory learning and action techniques e.g. chapati diagrams, pair-wise ranking. Secondary stakeholders representing local public-sector and non-governmental health and social care providers have formed a trial Stakeholders' Advisory Group (SAG), which includes two CAC representatives. RESULTS: Key recommendations from participatory community workshops, CAC and SAG meetings conducted in the first year of the trial relate to the quality and range of clinic services provided at study clinics as well as broader standard of care issues. Recommendations have included streamlining clinic services to reduce waiting times, expanding services to include the children and spouses of participants and providing care for common local conditions such as malaria. Participants, community representatives and stakeholders felt there was an ethical obligation to ensure effective access to antiretroviral drugs and to provide supportive community-based care for women identified as HIV positive during the trial. This obligation includes ensuring sustainable, post-trial access to these services. Post-trial access to an effective vaginal microbicide was also felt to be a moral imperative. CONCLUSION: Participatory methodologies enabled effective partnerships between researchers, participant representatives and community stakeholders to be developed and facilitated local dialogue and consensus on what constitutes a locally-appropriate standard of care in the context of a vaginal microbicide trial in this setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64716212

Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach

© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Introduction: There is currently a resurgence of levodopa as the initial treatment of choice for most patients with Parkinson's disease, albeit at lower doses than previously used. The addition of adjuvant treatments (including MAO-B inhibitors, COMT inhibitors and dopamine agonists) is an established strategy to reduce motor complications that develop with sustained levodopa therapy. Areas covered: In this narrative review, the authors discuss the evidence underpinning current levodopa optimization strategies, during early disease and once motor complications occur. To support the discussion, the authors performed a broad PubMed search with the terms 'levodopa/L-dopa/L-Dopa, and Parkinson's disease,' restricted to clinical trials. There is now a wealth of evidence that improving levodopa delivery to the brain improves outcomes and we discuss how agents can be combined earlier in the course of disease to leverage the full potential of this strategy. Expert opinion: Levodopa remains the cornerstone of antiparkinsonian therapy. Several promising advances in formulation have been made and include novel extended-release oral drugs as well as non-oral delivery systems. However, evidence has long suggested that anti-parkinsonian medications may be better used in combination earlier in the disease, and consequently patients will benefit from low doses of several agents rather than ever larger levodopa doses.This paper was supported by BIAL, who procured medical writing support but had no other influence on the content of the paper. No author received any remuneration for the preparation of this article.info:eu-repo/semantics/publishedVersio

Flickering Stimuli Do Not Reliably Induce Visual Hallucinations in Parkinson's Disease.

Visual hallucinations are a common and often distressing feature of Parkinson's disease; they are ephemeral and capricious, making them difficult to study but tend to be more prominent in dim illumination. Flickering stimuli can induce simple hallucinations even in healthy individuals. We tested a stroboscope and an equivalent full-screen flickering stimulus in 16 participants: 7 patients with Parkinson's and habitual visual hallucinations, 6 Parkinson's patients without hallucinations and 3 controls. Both flicker sources induced varied geometrical hallucinations in 4 participants (25%) and complex hallucinations in 1 but neither induced typical Parkinson's-associated hallucinations

Aplicando uma nova versão brasileira do UPSIT no Brasil

Standardized olfactory tests are now available to quantitatively assess disorders of olfaction. A Brazilian-Portuguese version of the University of Pennsylvania Smell Identification Test (UPSIT) is currently being developed specifically for the Brazilian population. The most recent Brazilian-Portuguese version of the UPSIT (UPSIT-Br2) was administered to 88 Brazilian subjects who had no history of neurological or otorhinolaryngological disease. UPSIT-Br2 scores decreased with age, were lower in men than in women, and were lower in subjects with lower income. The degree to which the poorer performance of subjects with lower socio-economic status reflects lack of familiarity with test items is not known. Although this version of the UPSIT provides a sensitive and useful test of smell function for the Brazilian population, a revision of some test items is needed to achieve comparable norms to those found using the North American UPSIT in the United States.Testes padronizados já estão disponíveis para testagem do olfato e uma versão em Português esta sendo desenvolvida para o University of Pennsylvania Smell Identification Test (UPSIT), especificamente para a população brasileira. A versão mais recente deste teste (chamada UPSIT-Br2) foi aplicada a 88 sujeitos brasileiros que não tinham história de qualquer problema neurológico ou otorrinolaringológico. Compatível com dados prévios da literatura, a performance no UPSIT-Br2 decaiu com a idade e foi inferior no genero masculino. Os resultados foram mais baixos em participantes de menor nível sócio-econômico e a relação deste achado com a falta de familiaridade para com os itens do teste não é conhecida. Apesar desta versão do UPSIT poder ser útil para o teste da função olfativa da população brasileira, a revisão de alguns itens se faz necessária para alcançar valores comparáveis aos dados normativos norte-americanos.Reta Lila Weston Trust for Medical Researc

Characterising the baseband impedance of supply modulators using simple modulated signals

Envelope tracking is one of the promising technologies for 5G power amplifiers, providing high power efficiency over a wide output power range by modulating the supply voltage. Although the baseband impedance, the output impedance of the supply modulator, plays a crucial role in the linearity of the PA, it is often not measured or considered during the modulator design. This paper presents a new, simplified approach to characterising this impedance using a PA with a simple multi-tone modulation as a load. It describes the measurement setup and verifies the results by characterising the baseband impedance of a state-of-the-art buck converter and comparing this to its static model. The results demonstrate that multi-tone signals and complex modulations yield comparable results and are both suitable for measuring and modelling the baseband impedance. This shows that using simple multi-tone measurements and basic equipment, the full static impedance characteristic can be obtained

Origins and population genetics of sambar deer (Cervus unicolor) introduced to Australia and New Zealand

Context. Some populations of introduced species cause significant undesirable impacts but can also act as reservoirs for genetic diversity. Sambar deer (Cervus unicolor) are ‘Vulnerable’ in their native range and invasive in Australia and New Zealand. Genetic data can be used to determine whether these introduced populations might serve as genetic reservoirs for declining native populations and to identify spatial units for management. Aims. We aimed to identify the provenance of sambar deer in Australia and New Zealand, and to characterise their genetic diversity and population structure. Methods. We used mitochondrial control region sequences and 18 nuclear microsatellite loci of 24 New Zealand and 63 Australian sambar deer collected across continuous habitat in each location. We estimated genetic diversity and population differentiation by using pairwise FST, AMOVA, and STRUCTURE analyses. We compared our data with 27 previously published native and invasive range sequences to identify phylogenetic relationships. Key results. Sambar deer in Australia and New Zealand are genetically more similar to those in the west of the native range (South and Central Highlands of India, and Sri Lanka), than to those in the east (eastern India, and throughout Southeast Asia). Nuclear genetic diversity was lower than in the native range; only one mitochondrial haplotype was found in each introduced population. Australian and New Zealand sambar deer were genetically distinct but there was no population structure within either population. Conclusions. The genetic differences we identified between these two introduced populations at putatively neutral loci indicate that there also may be underlying diversity at functional loci. The lack of population genetic structure that we found within introduced populations suggests that individuals within these popula- tions do not experience barriers to dispersal across the areas sampled. Implications. Although genetic diversity is reduced in the introduced range compared with the native range, sambar deer in Australia and New Zealand harbour unique genetic variants that could be used to strengthen genetic diversity in populations under threat in the native range. The apparent high levels of gene flow across the areas we sampled suggest that localised control is unlikely to be effective in Australia and New Zealand

Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome

Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC), cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS), warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes