435 research outputs found
Pole Dancing: 3D Morphs for Tree Drawings
We study the question whether a crossing-free 3D morph between two
straight-line drawings of an -vertex tree can be constructed consisting of a
small number of linear morphing steps. We look both at the case in which the
two given drawings are two-dimensional and at the one in which they are
three-dimensional. In the former setting we prove that a crossing-free 3D morph
always exists with steps, while for the latter steps
are always sufficient and sometimes necessary.Comment: Appears in the Proceedings of the 26th International Symposium on
Graph Drawing and Network Visualization (GD 2018
Enteric-coated sodium bicarbonate supplementation improves high-intensity cycling performance in trained cyclists
Purpose: Enteric-coated sodium bicarbonate (NaHCO3) can attenuate gastrointestinal (GI) symptoms following acute bicarbonate loading, although the subsequent effects on exercise performance have not been investigated. The purpose of this study was to examine the effects of enteric-coated NaHCO3 supplementation on high-intensity exercise performance and GI symptoms. Methods: Eleven trained male cyclists completed three 4 km time trials after consuming; a placebo or 0.3 g∙kg–1 body mass NaHCO3 in enteric-coated or gelatin capsules. Exercise trials were timed with individual peak blood bicarbonate ion concentration ([HCO3–]). Blood acid–base balance was measured pre-ingestion, pre-exercise, and post-exercise, whereas GI symptoms were recorded pre-ingestion and immediately pre-exercise. Results: Pre-exercise blood [HCO3−] and potential hydrogen (pH) were greater for both NaHCO3 conditions (P < 0.0005) when compared to placebo. Performance time was faster with enteric-coated (− 8.5 ± 9.6 s, P = 0.044) and gelatin (− 9.6 ± 7.2 s, P = 0.004) NaHCO3 compared to placebo, with no significant difference between conditions (mean difference = 1.1 ± 5.3 s, P = 1.000). Physiological responses were similar between conditions, although blood lactate ion concentration was higher with gelatin NaHCO3 (2.4 ± 1.7 mmol∙L–1, P = 0.003) compared with placebo. Furthermore, fewer participants experienced GI symptoms with enteric-coated (n = 3) compared to gelatin (n = 7) NaHCO3. Discussion: Acute enteric-coated NaHCO3 consumption mitigates GI symptoms at the onset of exercise and improves subsequent 4 km cycling TT performance. Athletes who experience GI side-effects after acute bicarbonate loading may, therefore, benefit from enteric-coated NaHCO3 supplementation prior to exercise performance.</p
Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs
The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples
TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease
A Theoretically Informed Process Evaluation in Parallel to a Feasibility Study of a Complex Oral Health Intervention Using NICE Guidelines in a Care Home Setting
\ua9 2025 The Author(s). Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.Background: A theoretically informed process evaluation was undertaken in parallel to a study examining the feasibility of an oral health intervention based on an existing guideline for care homes. The objectives were to explore the factors that influenced the implementation of the intervention in order to understand the potential pathway to impact. The research team initially utilised Pfadenhauer et al.\u27s framework, which focuses on a number of different implementation factors: intervention characteristics, context, theory, process, strategy, agents, outcomes and setting. Methods: Nine semi-structured interviews were undertaken with care home managers and staff, predominantly within the intervention arm of the study. Interview schedules were originally based on Pfadenhauer et al.\u27s framework. These were coded and analysed using thematic analysis. Given the range of themes that emerged, the research team ran a reflexive workshop to determine whether Pfadenhauer et al.\u27s framework was able to capture and frame the authentic voice of those interviewed. Results: The research team found that a systems lens approach better fitted the data from the interviews, capturing the idiosyncrasy of the different settings and the importance of values and beliefs of the key stakeholders. It was clear that unlike the structure proposed by Pfaednhauer et al., many of the factors were interdependent and hierarchical in nature, that is, paradigm and goals within the care home had a direct impact on the system structure, which fed into how the care home was maintained, which led onto how the different actors behaved (care home managers and staff). The process also highlighted key factors for intervention delivery: time poverty, competing needs, staff turnover, differences between shift patterns and between permanent and agency staff. Cognitive capacity of the residents and staff attitudes were also key. Conclusions: Adding a reflexive workshop enabled the research to critically review the Pfadenhauer et al.\u27s framework and change to a systems lens approach, which better explained the interdependent and hierarchical nature of the findings. It also highlighted a number of key factors that could influence the pathway to impact for the intervention. Trial Registration: ISRCTN10276613
Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.
Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
Upward Planar Morphs
We prove that, given two topologically-equivalent upward planar straight-line
drawings of an -vertex directed graph , there always exists a morph
between them such that all the intermediate drawings of the morph are upward
planar and straight-line. Such a morph consists of morphing steps if
is a reduced planar -graph, morphing steps if is a planar
-graph, morphing steps if is a reduced upward planar graph, and
morphing steps if is a general upward planar graph. Further, we
show that morphing steps might be necessary for an upward planar
morph between two topologically-equivalent upward planar straight-line drawings
of an -vertex path.Comment: Appears in the Proceedings of the 26th International Symposium on
Graph Drawing and Network Visualization (GD 2018) The current version is the
extended on
Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review
Background: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. Methodology/Principal Findings: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. Conclusion/Significance: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries
Athens by Sound
Architecture is not only that which is built. Architecture is made up of different aspects, both material and immaterial. The atmosphere, the sounds, the smells, the possibility of interaction between human bodies: these all constitute characteristics of space, characteristics that are assuming an increasing importance within architectural research worldwide. Within this field of thought about “Architecture Beyond Building”, we focus on one particular non-material spatial phenomenon that lies ‘beyond the built’: sound. We have created, thus, an interactive sonic map of Athens, which presents, in an unexpected way, fragments of the atmosphere of the city. What would a non-visual map look like? What would it feel like if you wandered within a forest of headphones, playing sounds from different places in Athens? How would it feel if you found yourself in a ‘map’ that only appeared when you walked in it? What would it be like if the map only appeared when you invited one more person to be with you? The Greek pavilion addresses these questions through an atmospheric interactive ‘game’, presenting fragments of sounds and visual sequences of Athens. The visitor recreates the space around him through his own presence and movement. The map appears only where he walks, and/or when he invites one more person to sit next to him. The bodies of the visitors react with one another and with the space itself, creating a dynamic, changing field. This walk in the pavilion takes you “out there”, through invisible Athens. The pavilion brings forth the aspects of architecture that are ‘beyond the material’: the ‘beyond the built’, the almost unreachable, elusive aspects of space, such as sound, non-visual senses, atmosphere. It challenges, thus, the limits of architecture, the limits of what can be mapped and re-located and what cannot. An edited collection by A. Karandinou, C. Achtypi, S. Giamarelos, including texts by: Ιntothepill, Katie Lloyd Thomas, Martin Parker, Panayiotis Tournikiotis, Mark Wigley, Dorian Wiszniewski, Leslie Kavanaugh, Stephen Cairns, Jonathan Hill, Vassilis Ganiatsas, Anastasios Kotsiopoulos, Constance Classen, Stavros Stavrides, Ole Bouman, William Mitchell, Richard Coyne, Neil Spiller, Kas Oosterhuis, Nora Schueler, Zissis Kotionis, Stelarc, Andreas Angelidakis, Aristide Antonas, Slavoj Žižek, Nikolaos Laskaris, Argyris Rokas, Andreas Kourkoulas, John Peponis, Yorgos Ioannou, Yorgos Tzirtzilakis, Konstantinos Vita, Dionyssis Kapsalis, United Visual Artists, Platon Rivellis, and Dimitris Filippidis. Contributors to the Greek National Participation to the 11th International Architecture Exhibition La Biennale di Venezia "Out there. Architecture beyond building" (2008) Organised by: Hellenic Ministry of Culture [yppo.gr] General Directorate of Modern Culture Directorate of Visual Arts Department for the Promotion of Contemporary Art Curators: Anastasia Karandinou Christina Achtypi Stylianos Giamarelos Video works by Intothepill net [intothepill.net] Artists: Yiannis Grigoriadis Yiannis Isidorou Lina Theodorou Sound Recording / Sound Design Dimitris Miyakis [movement.gr] Vangelis Lympouridis Exhibition Graphics / Catalogue Design Company [company-london.com] Design and Implementation of interactive environment 2monochannels [2monochannels.com] Audiovisual and interactive systems design / acoustic design / construction supervision Iraklis Lampropoulos Giorgos Lampropoulos Software programming Vassilis Boukis Electronic subsystem design Michail Kritsotakis Electrical Design Giorgos Satolias Interconnection of interactive elements Vangelis Lympouridis [inter-axions.com] Dimitris Miyakis Light design L+DG lighting architects [lightingdg.com] Thomas Gravanis Christina Frangeti Construction Gavrilos Michalis [gavrilos.gr] Digital printing Polichromo [polichromo.com] Translations Rachel Howard Nikos Masourides Catalogue photographs Intothepill – Internet video platform Catalogue published by futura publications Marketing communication Chryssa Vrouzi Communication associate Katerina Stamidi Photographer Cathy Cunliffe [cathycunliffeΑΤgmail.com] For their financial and material support for the Greek participation at the 11th International Exhibition of Architecture, La Biennale di Venezia, we express our deepest thanks to the sponsors: Alexander S. Onassis Public Benefit Foundation [onassis.gr] Akzonobel [akzonobel.com] Carteco - Architectural Materials & Design [carteco.gr] L+DG Lighting Architects [lightingdg.com] Plaisio [plaisio.gr] Polichromo Advertising Applications [polichromo.com] iGuzzini illuminazione [iguzzini.com] Diathlasis Architectural Lighting [diathlasis.gr
Expression of one important chaperone protein, heat shock protein 27, in neurodegenerative diseases
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