9,971 research outputs found
Computertomographie-basierte Bestimmung von Aortenklappenkalk und seine Assoziation mit Komplikationen nach interventioneller Aortenklappenimplantation (TAVI)
Background: Severe aortic valve calcification (AVC) has generally been recognized as a key factor in the occurrence of adverse events after transcatheter aortic valve implantation (TAVI). To date, however, a consensus on a standardized calcium detection threshold for aortic valve calcium quantification in contrast-enhanced computed tomography angiography (CTA) is still lacking. The present thesis aimed at comparing two different approaches for quantifying AVC in CTA scans based on their predictive power for adverse events and survival after a TAVI procedure.
Methods: The extensive dataset of this study included 198 characteristics for each of the 965 prospectively included patients who had undergone TAVI between November 2012 and December 2019 at the German Heart Center Berlin (DHZB). AVC quantification in CTA scans was performed at a fixed Hounsfield Unit (HU) threshold of 850 HU (HU 850 approach) and at a patient-specific threshold, where the HU threshold was set by multiplying the mean luminal attenuation of the ascending aorta by 2 (+100 % HUAorta approach). The primary endpoint of this study consisted of a combination of post-TAVI outcomes (paravalvular leak ≥ mild, implant-related conduction disturbances, 30-day mortality, post-procedural stroke, annulus rupture, and device migration). The Akaike information criterion was used to select variables for the multivariable regression model. Multivariable analysis was carried out to determine the predictive power of the investigated approaches.
Results: Multivariable analyses showed that a fixed threshold of 850 HU (calcium volume cut-off 146 mm3) was unable to predict the composite clinical endpoint post-TAVI (OR=1.13, 95 % CI 0.87 to 1.48, p=0.35). In contrast, the +100 % HUAorta approach (calcium volume cut-off 1421 mm3) enabled independent prediction of the composite clinical endpoint post-TAVI (OR=2, 95 % CI 1.52 to 2.64, p=9.2x10-7). No significant difference in the Kaplan-Meier survival analysis was observed for either of the approaches.
Conclusions: The patient-specific calcium detection threshold +100 % HUAorta is more predictive of post-TAVI adverse events included in the combined clinical endpoint than the fixed HU 850 approach. For the +100 % HUAorta approach, a calcium volume cut-off of 1421 mm3 of the aortic valve had the highest predictive value.Hintergrund: Ein wichtiger Auslöser von Komplikationen nach einer Transkatheter-Aortenklappen-Implantation (TAVI) sind ausgeprägte Kalkablagerung an der Aortenklappe. Dennoch erfolgte bisher keine Einigung auf ein standardisiertes Messverfahren zur Quantifizierung der Kalklast der Aortenklappe in einer kontrastverstärkten dynamischen computertomographischen Angiographie (CTA). Die vorliegende Dissertation untersucht, inwieweit die Wahl des Analyseverfahrens zur Quantifizierung von Kalkablagerungen in der Aortenklappe die Prognose von Komplikationen und der Überlebensdauer nach einer TAVI beeinflusst.
Methodik: Der Untersuchung liegt ein umfangreicher Datensatz von 965 Patienten mit 198 Merkmalen pro Patienten zugrunde, welche sich zwischen 2012 und 2019 am Deutschen Herzzentrum Berlin einer TAVI unterzogen haben. Die Quantifizierung der Kalkablagerung an der Aortenklappe mittels CTA wurde einerseits mit einem starren Grenzwert von 850 Hounsfield Einheiten (HU) (HU 850 Verfahren) und andererseits anhand eines individuellen Grenzwertes bemessen. Letzterer ergibt sich aus der HU-Dämpfung in dem Lumen der Aorta ascendens multipliziert mit 2 (+100 % HUAorta Verfahren). Der primäre klinische Endpunkt dieser Dissertation besteht aus einem aus sechs Variablen zusammengesetzten klinischen Endpunkt, welcher ungewünschte Ereignisse nach einer TAVI abbildet (paravalvuläre Leckage ≥mild, Herzrhythmusstörungen nach einer TAVI, Tod innerhalb von 30 Tagen, post-TAVI Schlaganfall, Ruptur des Annulus und Prothesendislokation). Mögliche Störfaktoren, die auf das Eintreten der Komplikationen nach TAVI Einfluss haben, wurden durch den Einsatz des Akaike Informationskriterium ermittelt. Um die Vorhersagekraft von Komplikationen nach einer TAVI durch beide Verfahren zu ermitteln, wurde eine multivariate Regressionsanalyse durchgeführt.
Ergebnisse: Die multivariaten logistischen Regressionen zeigen, dass die Messung der Kalkablagerungen anhand der HU 850 Messung (Kalklast Grenzwert von 146 mm3) die Komplikationen und die Überlebensdauer nicht vorhersagen konnten (OR=1.13, 95 % CI 0.87 bis 1.48, p=0.35). Die nach dem +100 % HUAorta Verfahren (Kalklast Grenzwert von 1421 mm3) individualisierte Kalkmessung erwies sich hingegen als sehr aussagekräftig, da hiermit Komplikationen nach einer TAVI signifikant vorhergesagt werden konnten (OR=2, 95 % CI 1.52 bis 2.64, p=9.2x10-7). In Hinblick auf die postoperative Kaplan-Meier Überlebenszeitanalyse kann auch mit dem +100 % HUAorta Verfahren keine Vorhersage getroffen werden.
Fazit: Aus der Dissertation ergibt sich die Empfehlung, die Messung von Kalkablagerungen nach dem +100 % HUAorta Verfahren vorzunehmen, da Komplikationen wesentlich besser und zuverlässiger als nach der gängigen HU 850 Messmethode vorhergesagt werden können. Für das +100 % HUAorta Verfahren lag der optimale Kalklast Grenzwert bei 1421 mm3
Examples of works to practice staccato technique in clarinet instrument
Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato
geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı
sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de
durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt
çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham
verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her
aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır.
Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine
yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini
içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin
kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür
taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de
kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt
çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve
güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının
girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken
doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir
kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına
bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği
vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan
çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur.
Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir.
Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır.
Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların
yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve
sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
School-based interventions to increase physical activity and reduce cardiometabolic risk in children
Omics measures of ageing and disease susceptibility
While genomics has been a major field of study for decades due to relatively inexpensive genotyping arrays, the recent advancement of technology has also allowed the measure and study of various “omics”. There are now numerous methods and platforms available that allow high throughput and high dimensional quantification of many types of biological molecules. Traditional genomics and transcriptomics are now joined by proteomics, metabolomics, glycomics, lipidomics and epigenomics.
I was lucky to have access to a unique resource in the Orkney Complex Disease Study (ORCADES), a cohort of individuals from the Orkney Islands that are extremely deeply annotated. Approximately 1000 individuals in ORCADES have genomics, proteomics, lipidomics, glycomics, metabolomics, epigenomics, clinical risk factors and disease phenotypes, as well as body composition measurements from whole body scans. In addition to these cross-sectional omics and health related measures, these individuals also have linked electronic health records (EHR) available, allowing the assessment of the effect of these omics measures on incident disease over a ~10-year follow up period. In this thesis I use this phenotype rich resource to investigate the relationship between multiple types of omics measures and both ageing and health outcomes.
First, I used the ORCADES data to construct measures of biological age (BA). The idea that there is an underlying rate at which the body deteriorates with age that varies between individuals of the same chronological age, this biological age, would be more indicative of health status, functional capacity and risk of age-related diseases than chronological age. Previous models estimating BA (ageing clocks) have predominantly been built using a single type of omics assay and comparison between different omics ageing clocks has been limited. I performed the most exhaustive comparison of different omics ageing clocks yet, with eleven clocks spanning nine different omics assays. I show that different omics clocks overlap in the information they provide about age, that some omics clocks track more generalised ageing while others track specific disease risk factors and that omics ageing clocks are prognostic of incident disease over and above chronological age.
Second, I assessed whether individually or in multivariable models, omics measures are associated with health-related risk factors or prognostic of incident disease over 10 years post-assessment. I show that 2,686 single omics biomarkers are associated with 10 risk factors and 44 subsequent incident diseases. I also show that models built using multiple biomarkers from whole body scans, metabolomics, proteomics and clinical risk factors are prognostic of subsequent diabetes mellitus and that clinical risk factors are prognostic of incident hypertensive disorders, obesity, ischaemic heart disease and Framingham risk score.
Third, I investigated the genetic architecture of a subset of the proteomics measures available in ORCADES, specifically 184 cardiovascular-related proteins. Combining genome-wide association (GWAS) summary statistics from ORCADES and 17 other cohorts from the SCALLOP Consortium, giving a maximum sample size of 26,494 individuals, I performed 184 genome-wide association meta-analyses (GWAMAs) on the levels of these proteins circulating in plasma. I discovered 592 independent significant loci associated with the levels of at least one protein. I found that between 8-37% of these significant loci colocalise with known expression quantitative trait loci (eQTL). I also find evidence of causal associations between 11 plasma protein levels and disease susceptibility using Mendelian randomisation, highlighting potential candidate drug targets
Women’s Experiences of Accessing Breastfeeding and Perinatal Health Support in the Context of Intimate Partner Violence: An Interpretive Description Study
Background: Women experiencing intimate partner violence are at a heightened risk of negative perinatal and breastfeeding outcomes. This study explored the experiences of accessing breastfeeding support for women who endorse a history of intimate partner violence. A study of five in-depth semi-structured interviews were completed at 12-weeks postpartum with breastfeeding mothers with a history of intimate partner violence. Findings: Women expressed difficulties in accessing a healthcare provider who had specialized skill in breastfeeding support. Trust in their healthcare provider, built through displays of compassion and competence, was important to mitigate obstacles experienced during care access for this population. Trauma-and-violence-informed care principles were beneficial to the development of the therapeutic relationship in perinatal care. Women placed value on breastfeeding support received from both healthcare providers and social supports, which impacted mothers’ perceived breastfeeding support and self-efficacy. Further, mothers described increased levels of breastfeeding self-efficacy after engaging in a trauma-and-violence-informed care program aimed at supporting breastfeeding. Conclusions: Trauma-informed care may aid in the development of trust in the therapeutic relationship, which in turn impacts access to breastfeeding support and breastfeeding self-efficacy. The inclusion of trauma-and-violence informed principles in perinatal care may be effective at mitigating barriers to access for women who endorse a history of intimate partner violence. health care on how to employ trauma-informed breastfeeding care to may lead to better support for this population
A comprehensive review on laser powder bed fusion of steels : processing, microstructure, defects and control methods, mechanical properties, current challenges and future trends
Laser Powder Bed Fusion process is regarded as the most versatile metal additive manufacturing process, which has been proven to manufacture near net shape up to 99.9% relative density, with geometrically complex and high-performance metallic parts at reduced time. Steels and iron-based alloys are the most predominant engi-neering materials used for structural and sub-structural applications. Availability of steels in more than 3500 grades with their wide range of properties including high strength, corrosion resistance, good ductility, low cost, recyclability etc., have put them in forefront of other metallic materials. However, LPBF process of steels and iron-based alloys have not been completely established in industrial applications due to: (i) limited insight available in regards to the processing conditions, (ii) lack of specific materials standards, and (iii) inadequate knowledge to correlate the process parameters and other technical obstacles such as dimensional accuracy from a design model to actual component, part variability, limited feedstock materials, manual post-processing and etc. Continued efforts have been made to address these issues. This review aims to provide an overview of steels and iron-based alloys used in LPBF process by summarizing their key process parameters, describing thermophysical phenomena that is strongly linked to the phase transformation and microstructure evolution during solidifica-tion, highlighting metallurgical defects and their potential control methods, along with the impact of various post-process treatments; all of this have a direct impact on the mechanical performance. Finally, a summary of LPBF processed steels and iron-based alloys with functional properties and their application perspectives are presented. This review can provide a foundation of knowledge on LPBF process of steels by identifying missing information from the existing literature
Industry 4.0: product digital twins for remanufacturing decision-making
Currently there is a desire to reduce natural resource consumption and expand circular business principles whilst Industry 4.0 (I4.0) is regarded as the evolutionary and potentially disruptive movement of technology, automation, digitalisation, and data manipulation into the industrial sector. The remanufacturing industry is recognised as being vital to the circular economy (CE) as it extends the in-use life of products, but its synergy with I4.0 has had little attention thus far. This thesis documents the first investigating into I4.0 in remanufacturing for a CE contributing a design and demonstration of a model that optimises remanufacturing planning using data from different instances in a product’s life cycle.
The initial aim of this work was to identify the I4.0 technology that would enhance the stability in remanufacturing with a view to reducing resource consumption. As the project progressed it narrowed to focus on the development of a product digital twin (DT) model to support data-driven decision making for operations planning. The model’s architecture was derived using a bottom-up approach where requirements were extracted from the identified complications in production planning and control that differentiate remanufacturing from manufacturing. Simultaneously, the benefits of enabling visibility of an asset’s through-life health were obtained using a DT as the modus operandi. A product simulator and DT prototype was designed to use Internet of Things (IoT) components, a neural network for remaining life estimations and a search algorithm for operational planning optimisation. The DT was iteratively developed using case studies to validate and examine the real opportunities that exist in deploying a business model that harnesses, and commodifies, early life product data for end-of-life processing optimisation. Findings suggest that using intelligent programming networks and algorithms, a DT can enhance decision-making if it has visibility of the product and access to reliable remanufacturing process information, whilst existing IoT components provide rudimentary “smart” capabilities, but their integration is complex, and the durability of the systems over extended product life cycles needs to be further explored
Application of advanced surface patterning techniques to study cellular behavior
Surface manipulation for the fabrication of chemical or topographic micro- and nanopatterns, has been central to the evolution of in vitro biology research. A high variety of surface patterning methods have been implemented in a wide spectrum of applications, including fundamental cell biology studies, development of diagnostic tools, biosensors and drug delivery systems, as well as implant design. Surface engineering has increased our understanding of cell functions such as cell adhesion and cell-cell interaction mechanics, cell proliferation, cell spreading and migration.
From a plethora of existing surface engineering techniques, we use standard microcontact printing methods followed by click chemistry to study the role of intercellular contacts in collective cancer cell migration. Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). The spreading of these colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts. We find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that in cancer cell migration, cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.
Despite the remarkable progress in surface engineering technology and its applications, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photo-immobilization technique, comprising a light-dose dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable pattering step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes, and that our innovative approach has a great potential for further applications in cell science.
In summary, this work introduces two novel and versatile paradigms of surface patterning for studying different aspects of cell behaviour in different cell types. The reliability of both setups is experimentally confirmed, providing new insight into the role of cell-cell contacts during collective cancer cell migration as well as the tip/stalk switch behaviour during angiogenesis
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