3,661 research outputs found
Metaanalyse zur genetischen PrÀdisposition bei Harnblasenkarzinomen anhand von Polymorphismen
Das Harnblasenkarzinom ist eine maligne Tumorerkrankung, die in den meisten FĂ€llen von
den Urothelzellen der Harnblase ausgeht. MÀnner sind von dieser Krebsart hÀufiger betroffen
als Frauen. In Deutschland ist es die vierthÀufigste Tumorlokalisation beim Mann und auf Platz
14 in der Krebsstatistik der Frau. Das relative 5-Jahres-Ăberleben betrĂ€gt bei MĂ€nnern
77 % und bei Frauen 72 % (2013).
Das Urothelkarzinom ist eine Erkrankung mit multifaktorieller Genese. Der Hauptrisikofaktor
fĂŒr Blasenkrebs ist Tabakkonsum mit einem signifikanten Einfluss auf Entstehung, Progression
und MortalitĂ€t. Etwa 50â65 % der mĂ€nnlichen und 20â30 % der weiblichen FĂ€lle sind auf
Tabakkonsum zurĂŒckzufĂŒhren. Einen weiteren Risikofaktor stellt die Exposition
gegenĂŒber aromatischen Aminen und polyzyklischen aromatischen Kohlenwasserstoffen dar,
die zwischen 7,1 % und 20 % der ErkrankungsfĂ€lle bedingen. AuĂerdem werden etwa
31 % der Blasentumoren durch genetische Risikofaktoren erklÀrt. In zahlreichen Studien
wurde der Einfluss von Einzelnukleotid-Polymorphismen auf das Erkrankungsrisiko fĂŒr das
Harnblasenkarzinom untersucht. Dabei kam es teils zu widersprĂŒchlichen Ergebnissen.
Im Rahmen dieser Dissertation wurde daher eine qualitative Auswertung aller bis zum
07.04.2020 auf PubMed veröffentlichten Fall-Kontroll-Studien durchgefĂŒhrt. AnschlieĂend
wurden die Arbeiten zu XRCC1 Arg399Gln (rs25487), ERCC2/XPD Lys751Gln (rs13181),
TP53 Arg72Pro (rs1042522), XRCC1 Arg194Trp (rs1799782), XRCC3 Thr241Met (rs861539)
und GSTP1 Ile105Val (rs1695) nÀher beleuchtet und deren Ergebnisse quantitativ in einer
Metaanalyse zusammengefasst. ZusÀtzlich wurden Subgruppenanalysen nach Ethnie und Art
der Kontrollpopulation durchgefĂŒhrt, um die Vergleichbarkeit der Studien zu steigern. Es wurde
jeweils die Odds Ratio und das 95 %-Konfidenzintervall berechnet.
FĂŒr GSTP1 Ile105Val wurde im rezessiven Modell eine Odds Ratio von 1,340 mit einem
95 %-Konfidenzintervall von 1,038â1,730 berechnet. Weiterhin konnte in den
SensitivitÀtsanalysen und verschiedenen Subgruppen bei den Polymorphismen XRCC1
Arg399Gln, TP53 Arg72Pro und XRCC1 Arg194Trp teilweise statistische Signifikanz erreicht
werden. Jedoch besteht diese Signifikanz nur fĂŒr einzelne Ethnien oder Studiendesigns und
lĂ€sst keine generelle Aussage ĂŒber die genetische PrĂ€disposition zu. FĂŒr ERCC2/XPD
Lys751Gln und XRCC3 Thr241Met zeigte sich in keinem der berechneten Modelle ein
statistisch signifikantes Ergebnis. Die Ergebnisse deuten darauf hin, dass TrÀger des GGGenotyps
(Val105) ein erhöhtes Risiko besitzen, an einem Harnblasenkarzinom zu erkranken.
Die Ergebnisse verdeutlichen die komplexe Ătiologie des Harnblasenkarzinoms als
multifaktorielle Erkrankung im Hinblick auf dessen genetische PrÀdisposition und Interaktion
mit zahlreichen Umweltfaktoren.Bladder cancer is a malignant tumour disease, which primarily originates from the urothelial
cells of the bladder. Men are more frequently affected by this type of cancer than women, but
the latter have a worse prognosis. In Germany it is the fourth most common tumour location in
men and 14th in the cancer statistics for women. The relative 5-year survival rate is 77 %
for men and 72 % for women (2013).
Urinary bladder cancer is a disease with a multifactorial genesis. Tobacco consumption is the
main risk factor for bladder cancer with a significant impact on its development, progression
and mortality. About 50â65 % of male and 20â30 % of female cases are caused by
smoking. The exposition to aromatic amines and polycyclic aromatic hydrocarbons
represents another risk factor, which causes between 7,1 % and 20 % of cases.
Furthermore, approximately 31 % of bladder tumours are explained by genetic risk factors.
Numerous studies have investigated the influence of different single nucleotide polymorphisms
on bladder cancer risk, with sometimes contradicting results.
Therefore, a qualitative analysis of all case-control studies published on PubMed until the 7th
of April 2020 was conducted in the context of this thesis. Subsequently, the publications
concerning XRCC1 Arg399Gln (rs25487), ERCC2/XPD Lys751Gln (rs13181), TP53 Arg72Pro
(rs1042522), XRCC1 Arg194Trp (rs1799782), XRCC3 Thr241Met (rs861539) and GSTP1
Ile105Val (rs1695) were further examined and quantitatively summarized in a meta-analysis.
Additionally, subgroup analysis by ethnicity and source of controls were performed, to enhance
the comparability of the studies. In each case, the odds ratio and the 95 %-confidence interval
were calculated.
For GSTP1 Ile105Val an odds ratio of 1,340 with a 95 %-confidence interval from 1,038 to
1,730 was calculated in the recessive model. Furthermore, statistical significance was partially
achieved in the sensitivity analyses and various subgroups for the polymorphisms XRCC1
Arg399Gln, TP53 Arg72Pro and XRCC1 Arg194Trp. However, this significance only consists
in several ethnicities or study designs and does not allow a general statement about genetic
predisposition. No significant results were found in any of the calculated models for
ERCC2/XPD Lys751Gln and XRCC3 Thr241Met. The findings indicate that carriers of the GG
genotype (Val105) have an increased risk of developing bladder cancer. The results illustrate
the complex etiology of bladder cancer as a multifactorial disease in terms of its genetic
predisposition and interaction with numerous environmental factors
Positioning urban labs â a new form of smart governance?
In the current era, in which cities are considered key arenas for coping with a number of societal challenges, there is also renewed interest in the mobilisation of experimental practices within urban planning. A growing interest in innovative intiatives emphasising co-creation, exploration, experimentation, and evaluation, such as urban living labs must also be understood in relation to the uncertatinity regarding the modern growth paradigm and its institutional arrangements: âthe pragmatist heritage of urban laboratories gains renewed strength in the current era in which the belief in modernity, progress and development is in crisisâ (Karvonen & van Heur, 2014, p. 387). This paper provides a sympathetic critique of the notion of urban living labs and related expeimental practices from an urban planning and governance persepective. In this light, we argue that the core principels of urban living labs (i.e. co-creation, exploration, experimentation, and evaluation) offer a useful theortical frame to understand and position different informal self-organizing initiatives in contemporary urban development. Furthermore, we assert that, considered as a planning practice (or methodology), urban living labs can be construed as a temporary mode of soft governance which include a number of merits in terms of definig new innovative pathways for urban planning beyond business as usual thinking. However, caution must be taken due to the urban living labâs inherent shortcomings in terms of demorcractic legitimacy, tendencies towards exclusiveness, and extreme temporality. In conclusion, we argue that urban living labs can be an environment for exploring new forms of smart urban governance through critical engagments with communicative planning theory and an explict focus on actor-relations
Urban Planning through Exhibition and Experimentation in Stockholm
In this paper we discuss findings of our case study on the making and implementation of the exhibition 'Experiment Stockholm' in 2015, which, based on artistic exhibits as well as a number of forums, aimed at generating creative narratives for the sustainable urban future in the Swedish capital city-region. Our analytical framework is informed by the emerging notion of 'urban living labs' across Europe as well as 'communicative' and 'actor-relational' planning theory', which is discussed in another paper within the poceedings of this conference (cf. Schmitt et al. 2016). We argue that the exhibition 'Experiment Stockholm' and the activities around it can be characterised as a soft mode of urban governance that can help to unlock creativity and to open up avenues for experimentation and alternative solutions in urban planning. However, caution must be taken to not overvalue such approaches, as our example implies a rather exclusive expert forum instead of a a mode of governance that might be associated with openness and wider engagement. In addition, our example illustrates the significance of suitable and unconventional methods, which otherwise considerably limits the innovative capacity of the participating stakeholders and their search for alternative solutions
Graphical smalltalk with my optimization system for urban planning tasks
Based on the description of a conceptual framework for the representation of planning problems on various scales, we introduce an evolutionary design optimization system. This system is exemplified by means of the generation of street networks with locally defined properties for centrality. We show three different scenarios for planning requirements and evaluate the resulting structures with respect to the requirements of our framework. Finally the potentials and challenges of the presented approach are discussed in detail
Adjektivgebrauch in Bildbeschreibungen â Eine korpuslinguistische Untersuchung zum Gebrauch von Adjektiven in Texten von SchĂŒlerinnen und SchĂŒlern
In this article, written descriptions by students in the third to sixth grade (N = 288) are examined with regard to the use of syntactically differently integrated and differently complex adjectives. Descriptively, attributive adjectives were used most frequently and participially attributive adjectives were used least frequently. The use of different adjectives correlated positively with each other almost universally across the sample. The use of attributive adjectives increased significantly with increasing age. The use of participial attributive, adverbial, compositional, and derivative adjectives was significantly associated with increasing grade level. The use of compositional and derivative adjectives was significantly associated with increasing grade level. Predicative adjective use did not differ significantly between grades. The results provide important insights into the language acquisition process of adjectives and give indications for didactic starting points for teaching text-sort-specific word types
ADJEKTIVE IN BILDBESCHREIBUNGEN. Eine Korpuslinguistische Untersuchung zum Adjektivgebrauch von bilingual und monolingual aufwachsenden SchĂŒlerinnen und SchĂŒlern
Im vorliegenden Beitrag werden schriftliche Bildbeschreibungen von monolingual und bilingual aufwachsenden SchĂŒler*innen der dritten bis sechsten Klasse (N = 288) hinsichtlich ihres Adjektivgebrauchs untersucht. Deskriptiv zeigt sich, dass monolinguale SchĂŒler*innen mehr Adjektive in der Freitextproduktion verwenden als bilinguale SchĂŒler*innen. Mit Ausnahme der prĂ€dikativen und wertenden Adjektive, die prĂ€dikativ und attributiv vorkommen, zeigt sich ein vermehrter Adjektivgebrauch bei monolingual Lernenden im Vergleich zu bilingual Lernenden. FĂŒr die prĂ€dikativen Adjektive zeigen sich keine signifikanten Unterschiede; fĂŒr die wertenden Adjektive zeigt sich ein Mehrgebrauch der bilingualen SchĂŒler*innen. Die gefundenen Effekte können als klein bis mittel klassifiziert werden. Es zeigt sich keine Evidenz fĂŒr das Vorliegen einer Interaktion zwischen Spracherwerb und Klassenstufe in der Verwendung attributiver und wertender Adjektive. Die Auswertung liefert wichtige Erkenntnisse zum Sprachaneignungsprozess von Adjektiven und zeigt schulischen Handlungsbedarf auf
Cross-Linking Strategies for Fluorine-Containing Polymer Coatings for Durable Resistant Water- and Oil-Repellency
Functional coatings for application on surfaces are of growing interest. Especially in the
textile industry, durable water and oil repellent finishes are of special demand for implementation
in the outdoor sector, but also as safety-protection clothes against oil or chemicals. Such oil and
chemical repellent textiles can be achieved by coating surfaces with fluoropolymers. As many
concerns exist regarding (per)fluorinated polymers due to their high persistence and accumulation
capacity in the environment, a durable and resistant coating is essential also during the washing
processes of textiles. Within the present study, different strategies are examined for a durable
resistant cross-linking of a novel fluoropolymer on the surface of fibers. The monomer 2-((1,1,2-
trifluoro-2-(perfluoropropoxy)ethyl)thio)ethyl acrylate, whose fluorinated side-chain is degradable
by treatment with ozone, was used for this purpose. The polymers were synthesized via free radical
polymerization in emulsion, and different amounts of cross-linking reagents were copolymerized.
The final polymer dispersions were applied to cellulose fibers and the cross-linking was induced
thermally or by irradiation with UV-light. In order to investigate the cross-linking efficiency, tensile
elongation studies were carried out. In addition, multiple washing processes of the fibers were
performed and the polymer loss during washing, as well as the effects on oil and water repellency
were investigated. The cross-linking strategy paves the way to a durable fluoropolymer-based
functional coating and the polymers are expected to provide a promising and sustainable alternative
to functional coatings
Thalamic reticular impairment underlies attention deficit in Ptchd1Y/â mice
Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in âŒ1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post-natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN-restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention.Simons Foundation Autism Research Initiative (Grant 307913)National Institutes of Health (U.S.) (Grant R01MH097104)National Institute of Mental Health (U.S.) (Grant R01MH097104)National Institutes of Health (U.S.) (Grant R01MH107680
Impact of a clinical decision support system on paediatric drug dose prescribing: a randomised within-subject simulation trial
BACKGROUND
Drug dosing errors are among the most frequent causes of preventable harm in paediatrics. Due to the complexity of paediatric pharmacotherapy and the working conditions in healthcare, it is not surprising that human factor is a well-described source of error. Thus, a clinical decision support system (CDSS) that supports healthcare professionals (HCP) during the dose prescribing step provides a promising strategy for error prevention.
METHODS
The aim of the trial was to simulate the dose derivation step during the prescribing process. HCPs were asked to derive dosages for 18 hypothetical patient cases. We compared the CDSS PEDeDose, which provides a built-in dose calculator to the Summary of Product Characteristics (SmPC) used together with a pocket calculator in a randomised within-subject trial. We assessed the number of dose calculation errors and the time needed for calculation. Additionally, the effect of PEDeDose without using the built-in calculator but with a pocket calculator instead was assessed.
RESULTS
A total of 52 HCPs participated in the trial. The OR for an erroneous dosage using the CDSS as compared with the SmPC with pocket calculator was 0.08 (95% CI 0.02 to 0.36, p<0.001). Thus, the odds of an error were 12 times higher while using the SmPC. Furthermore, there was a 45% (95% CI 39% to 51%, p<0.001) time reduction when the dosage was derived using the CDSS. The exploratory analysis revealed that using only PEDeDose but without the built-in calculator did not substantially reduce errors.
CONCLUSION
Our results provide robust evidence that the use of the CDSS is safer and more efficient than manual dose derivation in paediatrics. Interestingly, only consulting a dosing database was not sufficient to substantially reduce errors. We are confident the CDSS PEDeDose ensures a higher safety and speeds up the prescribing process in practice
Graphical smalltalk with my optimization system for urban planning tasks
Based on the description of a conceptual framework for the representation of planning problems on various scales, we introduce an evolutionary design optimization system. This system is exemplified by means of the generation of street networks with locally defined properties for centrality. We show three different scenarios for planning requirements and evaluate the resulting structures with respect to the requirements of our framework. Finally the potentials and challenges of the presented approach are discussed in detail
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