202 research outputs found
Fluid Biomarkers in the Frontotemporal Dementia Spectrum
No full textFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder, comprising a spectrum of subtypes that are different on the clinical, genetic and pathological level. Clinically, symptoms typically present before the age of 65 and include behavioural and/or language disturbances, yet also motor problems frequently occur. FTD can be heritable, and 10-20% of the patients have an autosomal dominant form, which is most frequently caused by a mutation in granulin (GRN, also known as progranulin), in microtubule-associated protein tau (MAPT), or a repeat expansion in chromosome 9 open reading frame 72 (C9orf72). Pathological examination shows frontotemporal lobar degeneration (FTLD) with inclusions of either TAR DNA-binding protein 43 (FTLD-TDP), tau (FTLD-tau), or FET (fused in sarcoma, Ewing’s sarcoma and TAT-binding protein-associated factor 15).
Currently, major advances are being made to develop therapeutic interventions for FTD. However, the heterogeneity of this disorder hampers the diagnostic process, tracking of disease progression, and the appropriate selection of patients for clinical trials. Reliable biomarkers are therefore critically needed. This thesis investigated the utility of biomarkers in cerebrospinal fluid (CSF) and blood, so-called fluid biomarkers, across the entire FTD spectrum. The thesis has shown that NfL is a promising biomarker in CSF and in blood across the entire FTD spectrum, both in sporadic and genetic forms. NfL levels are higher in patients than controls and can thus be used to ascertain disease. Also, NfL could monitor disease severity and progression and predicts survival – valuable information for the individual patient – in most subtypes within the FTD spectrum, except for svPPA. To select patients on underlying proteinopathy, the p/t-tau ratio may be useful being decreased in FTLD-TDP versus FTLD-tau, but more discriminative markers are needed. Our CSF proteomics study in GRN mutations identified potential novel biomarkers and provides knowledge of the pathophysiology of GRN mutations. Lastly, for FTD caused by GRN mutations or C9orf72 repeat expansions, PGRN and poly(GP) respectively identify mutation carriers and are target engagement markers for clinical trials that are underway. Our results facilitate the implementation of these biomarkers for clinical or research purposes, and provide additional understanding of the pathophysiological process underlying FTD, opening new avenues towards treating FTD
Poetry, illness, social criticism. Lieke Marsman's De volgende scan duurt vijf minuten as a case study: analysis, translation and commentary.
No full textreservedL'elaborato si propone innanzitutto di fornire una visione generale dell'autrice e poetessa contemporanea neerlandese Lieke Marsman, passando in rassegna le sue opere, dagli esordi al giorno d'oggi. In particolare, il focus sarà posto sul libro "De volgende scan duurt vijf minuten", pubblicato nel 2018 e composto da poesie e saggio autobiografico. Nella seconda parte dell'elaborato si riporteranno i punti cardine dei translation studies, specialmente in relazione alla traduzione della poesia, e verrà presa in analisi la traduzione del libro proposta dalla sottoscritta, prestando particolare attenzione al pubblico target, alle modalità di traduzione e alla riflessione su determinate problematiche riscontrate relativamente al linguaggio medico più specifico all'interno del mondo letterario. Quest'ultimo tema sarà al centro di una riflessione conclusiva e ulteriormente ampliabile sulla relazione tra malattia e letteratura.The paper will firstly aim to provide an overview of the contemporary Dutch author and poet Lieke Marsman, going through her works from her beginnings to the present day. In particular, the focus will be on the book 'De volgende scan duurt vijf minuten', published in 2018, made out of poems and autobiographical essay. In the second part of the paper, the key points of translation studies will be reported, especially with regard to the translation of poetry. The translation of the book proposed by the author of this paper will be then analysed, paying particular attention to the target audience, the translation procedure and the consideration on problems encountered in relation to the more specific medical language within the literary world. This latter theme will be the focus of a concluding and further expandible reflection on the relationship between illness and literature
The Following Scan Will Last Five Minutes
No full textIn The Cancer Journals Audre Lorde wrote, ‘I do not wish my anger and pain and fear about cancer to fossilise into yet another silence, not to rob me of whatever strength can lie at the core of this experience, openly acknowledged and examined.’ Founded on this same principle, The Following Scan Will Last Five Minutes was written in the three months following Dutch writer Lieke Marsman’s cancer diagnosis. A series of short poems anchored by an essay that speaks directly to Lorde’s journal entries and personal reflections on cancer, Marsman considers, among other things, the state of contemporary Dutch politics and – via Susan Sontag’s Illness as Metaphor – the rhetoric surrounding her disease. A work of poetry, social criticism and autobiography, The Following Scan is an honest and dryly comic account of a period in the author’s life that elides pretension in search of autonomy and self-knowledge. Beautifully translated by the poet Sophie Collins, the book also includes a translator’s note in the form of a letter to her author and friend
Visualising Female Authorship. Author Portraits and the Representation of Female Literary Authority in the Eighteenth-Century Dutch Republic
No full textsponsorship: This research was supported by NWO Rubicon grant nr. 019.173SG.017. The author wishes to thank Nina Lamal, Kim Overlaet, Jan Rotmans and Katlijne Van der Stighelen for their feedback on a previous version of this article. (NWO Rubicon grant|019.173SG.017)status: Publishe
Cultural Branding in the Early Modern Period: The Literary Author
No full textThe early modern commercial book market was the cradle of authorial branding. Authors and publishers increasingly explored the construction of authorial brands: a set of recurring and recognizable characteristics associated with authorial images. This chapter looks at branding in the context of the media landscape of the early modern Dutch Republic. Authorial branding developed over time in conjunction with new conceptions of the individual, technological innovations, and the changing role of – amongst others – patrons and publishers. Analyses of the branding of Jan Jansz. Starter (1593-1626) and Sara Maria van der Wilp (1716-1803) illustrate how the non-formalized, dynamic constellation of the literary f ield inspired various agents to create a range of (multifaceted) author brands on the spectrum ‘economic-symbolic’
Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics
No full textAbstractIntroductionReliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking.MethodsUnbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18).ResultsOf 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P < .05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB.DiscussionWe identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development
Measuring Motor Fatigability in the Upper Limbs in Individuals With Neurologic Disorders: A Systematic Review
No full textOBJECTIVE: To summarize the literature on definitions, assessment protocols, and outcome measures for motor fatigability in patients with neurologic problems and investigates the known clinimetric properties according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. DATA SOURCES: Two databases were consulted for studies published between January 2003 and November 2018 using the terms "motor fatigability," "nervous system disease," and "upper limb." STUDY SELECTION: Studies were included if they were (1) not older than 15 years; (2) written in English, German, or Dutch; (3) involved upper limbs of patients with neurologic disease; and (4) adequately described protocols using maximum voluntary contractions. DATA EXTRACTION: Thirty-three studies were included, describing 14 definitions, 37 assessment protocols, and 9 outcome measures. The following data were obtained: (1) author and publication year; (2) aim; (3) fatigability definition; (4) sample characteristics; (5) fatigability protocol; (8) measurement system; and (9) outcome measure. DATA SYNTHESIS: Protocols relating to body function level of the International Classification of Functioning (ICF) were most often performed in patients with multiple sclerosis (MS) including maximal or submaximal, isometric or concentric, and eccentric contractions of variable duration. For ICF activities level, most protocols included wheelchair-related tasks. Clinimetric properties were known in 2 included protocols. Test-retest reliability in patients with MS were moderate to excellent for the static fatigue index and moderate for the dynamic fatigue index. CONCLUSIONS: Based on physiology, recommendations are made for protocols and outcome measures for motor fatigability at the ICF body function level. For the ICF activities level, too little is known to make sound statements on the use of protocols in populations with neurologic disease. Clinimetric properties should be further investigated for populations with neurologic problems.sponsorship: Supported by the Bijzonder Onderzoeksfonds by UHasselt (grant no. BOF17NI07). (Bijzonder Onderzoeksfonds by UHasselt|BOF17NI07)status: Publishe
Design Requirements for Future Technology to Enhance Surgical Instrument Counting: An Observational Study at the Reinier de Graaf Gasthuis
No full textINTRODUCTION Surgical counting of instruments forms a crucial part of safety procedures in the operating room (OR). This process has remained primitive without technological support. The manual count process is time-consuming and places heavy cognitive demands on nurses. Current technological approaches fail to detect the exact and detailed usage of surgical instruments under real-life OR conditions. This research aims to enhance surgical instrument counting in the hospital by identifying challenges in the pre-operative, intra-operative, and postoperative phases and formulating design requirements for future technology. METHODS An observational study was conducted in a large teaching hospital in Delft. The process of surgical instrument counting was assessed in the pre-operative, intra-operative, and postoperative phases of 50 surgeries. Nurses were surveyed to assess the method used, the experienced workload, and the willingness to adopt technology for surgical counting. The sterilization department provided data on the number of additional surgical instruments found on surgical trays after surgery and data on the different types of surgical trays delivered to the hospital. RESULTS In all surgeries, surgical instrument counting was not performed according to the hospital’s protocol due to limited time and resources. Nurses used a technique to memorize the surgical instrument count by placing the surgical instruments in even numbers on the surgical instrument table. Surgical instruments were retrieved from their original surgical tray and placed on a surgical instrument table in case of frequent use or retrieved from their surgical tray and promptly handed to the surgeon in case of infrequent use. The return of surgical instruments to the surgical trays occurred intermittently, mostly when the surgical instrument was not deemed necessary anymore for the remaining surgery. After sterilization, occasionally incomplete surgical trays arrived at the hospital (10,0%), necessitating additional surgical trays to be added to the sterile field. During a 16-week timeframe, 801 additional surgical instruments were found on surgical trays indicating they were not returned to their original surgical tray. All nurses were willing to adopt technology for surgical counting, specifically in the pre-and postoperative phases. CONCLUSION This study highlighted the challenge of balancing protocol, ensuring patient safety, and working efficiently. A control measure for the initial and final surgical instrument count is necessary for every surgery, as the current technique is insufficient. The design requirements for future technology are monitoring counts in the preparation room (PR) and OR, adjusting to accommodate additional surgical trays, having a focal area on the surgical tray, and identifying incomplete surgical trays. Future technology could enhance surgical instrument counting at the Reinier de Graaf Gasthuis by ensuring the presence and return of used surgical instruments to their original surgical tray.Biomedical Engineerin
Retail areas in the city: From a place to buy to a place to be
No full textThe goal of the project is ‘to make retail areas go from a place to buy to a place to be’. Retail environments have the potential to become a place to be and add value for visitors, the local community and society as a whole. After performing research on various different levels, both quantitative and qualitative and both with consumers and external stakeholders, new consumer vales emerged for retail areas in the city. They were transparency, connection, atmosphere, exploration and authenticity. Exploration and authenticity were chosen as the two core values to form a design direction. A conceptual model was produced to add value to retail areas: in order to create a place to be, a story and an experience are necessary. The story is what brings authenticity to a place, and that can be achieved using storytelling. An experience can be created through multisensory design and can provide the core value of exploration. Using this model, a possible design was created: the story box. This concept provides a multisensory storytelling experience. The story box is a physical cube placed in the street that tells a story through exploration. Users move around the cube to go through the stages of the discovery process: touch, see and hear.The three sides of the cube are assigned with different colors: green, red and blue. Users then can step inside the box and hear the full story. The experience is not just limited to interacting with the cube, it is extended to interacting with the entire street. Both the effect of the authentic stories and the exploring discovery are extended into the street. For the authentic stories, in addition to the large cube, small cubes using the same colors are placed throughout the street at the entrance of shops and stores. Shopowners can participate in the project and adopt a small cube. These small cubes provide the story of the shop or store in audio, once a visitor places its hand inside the cube. For the exploring journey, small colored tiles are placed on the facades throughout the street. The colors coordinate with the colors of the interactions with the cube: touch, see and hear. The small tiles each provide another little discovery journey: green tiles mean there is something nice to touch, red tiles meansthere is something nice to see and blue tiles mean there is something to hear. The final concept gives meaning to retail areas and provides and authentic story in an exploring way. Design for Interactio
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