Number of results to display per page
Search Results
26982. The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors
- Creator:
- Demlova, R., Valík, D., Obermannova, R., and Zdražilová-Dubská, L.
- Type:
- article, model:article, and TEXT
- Subject:
- Camcer treatment, Monoclonal antibodies, Immune chceckpoint inhibitors, and Immune related adverse events
- Language:
- English
- Description:
- Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC. Based on their mechanism of action, these agents can exert toxicities that are unlike conventional cytotoxic chemotherapy, whose nature is close to autoimmune diseases - immune related adverse events (irAEs). In this review we focus on the spectrum of irAEs associated with immune checkpoint antibodies, discussing the pharmacological treatment strategy and possible clinical impact.
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
26983. The selection of ceramic raw material: convenience or a technological idea?: a case study of the Danubian cultures north of the Carpathians
- Creator:
- Kadrow, Sławomir and Rauba-Bukowska, Anna
- Type:
- article, model:article, and TEXT
- Subject:
- LBK, ALPC, trans-Carpathian contacts, pottery, clay raw materials, technological analysis, trans-karpatské kontakty, keramika, keramické suroviny, and technologická analýza
- Language:
- Czech
- Description:
- This paper reconstructs the rules governing the selection of ceramic raw material and considers certain technological aspects of the production of ceramic vessels in some Danubian cultures around the Carpathians in the Neolithic. The analysis encompassed more than 500 samples of ceramics produced by various cultural units across different chronological horizons. The results of the analysis are used to verify several hypotheses concerning the relationships and the mechanisms of cultural change in the Carpathian region. The most important questions include: (1) evolution of the LBK ceramics, (2) influence of the ALPC on the evolution of the LBK pottery in Małopolska, (3) technology of the LBK ceramics east of the Carpathians, (4) culture change at the turn of the LBK and the MC in Małopolska and (5) culture change at the turn of the MC and the L-VC in the same region. The suitability of the pottery technological analysis to solve some prehistoric problems was confirmed. and Článek rekonstruuje pravidla ovládající výběr keramických surovin a zvažuje určité technologické aspekty výroby keramických nádob v některých podunajských kulturách neolitu v oblasti Karpat. Analyzováno bylo více než 500 keramických vzorků vytvořených různými kulturními jednotkami různých chronologických horizontů. Výsledky analýzy slouží k ověření několika hypotéz týkajících se souvislostí a mechanismů kulturní změny v karpatské oblasti. Mezi nejdůležitější otázky patří: (1) vývoj LBK keramiky, (2) vliv ALPC na vývoj LBK keramiky v Malopolsku, (3) technologie LBK keramiky východně od Karpat, (4) kulturní změna na přechodu mezi LBK a MC v Malopolsku, (5) kulturní změna na přechodu mezi MC a L-VC v téže oblasti. Výsledky potvrzují vhodnost analýzy technologie keramiky pro objasnění některých otázek pravěku.
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
26984. The sense of life as a subjective spiritual human experience: empirical study
- Creator:
- Ryś, Ewa
- Type:
- article, model:article, and TEXT
- Subject:
- spirituality, sense of meaning in life, and logotheory
- Language:
- Czech
- Description:
- Man’s spirituality is part of individual inner experience e.g. awareness of making one’s own choices, subjectivity, aspirations, preferred values and their criteria, open-mindedness towards oneself and others, readiness to contradict evil, and striving to realize the purpose of life. The multifaceted construct of SoL embraces: 1) life affirmation, 2) self-acceptance, 3) goal awareness, 4) sense of freedom, 5) valuation of future, and 6) attitude towards death. The objective of my empirical research was to determine the intensity of SoL among students of pedagogy and to establish which components of meaning of life co-condition the level of SoL intensity. Test group : a representative group of pedagogy students at the University of Szczecin: 683 people. The designed SoL test is based on the PIL (Purpose in Life) format- Crumbaugh-Maholick Purpose-in-Life Test. The results of research prove empirical theses stated on the grounds of logotheory and logotherapy (e.g. about the significance of the attitude towards death for the attitude towards life, and the sense of freedom as a mechanism facilitating transcendence).
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
26985. The significance of (CA)n tandem repeat in GABA(A) Beta‑3 subunit gene in tinnitus manifestation
- Creator:
- Rottenberg, Jan, Zallmann, M., Kostřica, Rom, Jurajda, Michal, and Talach, Tomáš
- Format:
- print, text, and regular print
- Type:
- model:article, article, Text, práce podpořená grantem, and TEXT
- Subject:
- tinnitus--diagnóza--genetika, evokované potenciály sluchové--fyziologie--genetika, receptory GABA-A--fyziologie--genetika, mozkový kmen--fyziologie, polymorfismus jednoho nukleotidu--genetika, genotyp, koncové repetitivní sekvence--genetika, sluchový práh--fyziologie, audiometrie čistými tóny--využití, akustická stimulace--metody, sluchové dráhy--fyziologie, dospělí, staří, ženské pohlaví, lidé, mužské pohlaví, and lidé středního věku
- Language:
- Czech and English
- Description:
- Cíl studie: Cílem studie bylo zjištění vztahů mezi manifestací tinnitu, nálezem na sluchových evokovaných potenciálech a genetickým pozadím u receptoru pro gamaaminomáselnou kyselinu typu A (GABA(A) receptor), podporující desinhibiční hypotézu vzniku tinnitu. Soubor a metodika: Bylo vyšetřeno 131 pacientů z hlediska sluchové ztráty, provedena kvantifikace tinnitu, sluchové evokované potenciály střední latence (MLR) a kmenové sluchové evokované potenciály (BAEP) a dále stanovení genotypu (CA)n repetitivní sekvence pro beta‑3 podjednotku GABA(A) receptoru. Následně byly hledány vztahy mezi jednotlivými výsledky a manifestací tinnitu. Výsledky: Byla nalezena korelace tinnitus skóre s amplitudovým poměrem vln V/III v BAEP (R = 0,22, p < 0,001) a s průměrným sluchovým prahem (R = 0,22, p = 0,17). Rovněž byla nalezena korelace tinnitus skóre s amplitudou vlny PA v MLR (R = 0,31–0,37; p < 0,001). Výsledky MLR neukázaly žádný vztah k průměrnému sluchovému prahu. U skupiny s kratší anamnézou tinnitu (méně než devět měsíců) byl prokázán rozdíl v manifestaci tinnitu na genotypu pro (CA)n repetitivní sekvenci genu pro beta‑3 podjednotku GABA(A) receptoru (p = 0,002). Tento výsledek byl rovněž konzistentní s rozložením amplitudy vlny PA v dané subpopulaci. Závěr: Tyto výsledky svědčí o existenci dvou hlavních regulačních mechanizmů vzniku tinnitu: první, který je závislý na velikosti sluchové ztráty, je na úrovni mozkového kmene, zatímco druhý je na úrovni korové s možnou souvislostí s genotypem (CA)n repetitivní sekvence pro beta‑3 podjednotku GABA(A) receptoru., Study aim:Study objective was to explore associations between manifestation of tinnitus, auditory evoked potentials and genetic background of gamma‑aminobutyric acid type A (GABA(A) receptors) to support the disinhibited feedback hypothesis of tinnitus generation. Materials and methods: A population of 131 patients was assessed for severity of hearing loss, quantification of tinnitus, mid‑latency responses (MLR) and brainstem auditory evoked potentials (BAEP), and (CA)n tandem repeat polymorphism in GABA(A) Beta‑3 subunit gene to establish any correlation with manifestation of tinnitus. Results: It was observed that tinnitus score correlates with V/III amplitude ratio in BAEP (R = 0.22, p < 0.001) and with mean pure tone audiometry (PTA) threshold (R = 0.22, p = 0.017). Analysis of the MLR results showed a significant correlation between the PA wave amplitude and the tinnitus score (R = 0.31–0.37; p < 0.001). MLR result analysis showed no statistically significant correlation between the wave amplitudes and the mean auditory threshold. An analysis of a subgroup with shorter clinical history (less than nine months) revealed a statistically significant difference in the tinnitus score in relation to the genotype of (CA)n tandem repeat of the GABRß3 receptor subunit gene (p = 0.002). This result was also consistent with the distribution of the PA wave amplitude in the given subpopulation. Conclusion: Our findings indicate existence of two main regulatory mechanisms of tinnitus generation: first, the brainstem mechanism is dependent on the severity of the hearing loss; second, the cortical mechanism is likely to be dependent on the genotype of (CA)n tandem repeat in GABA(A) beta‑3 subunit gene., and J. Rottenberg, M. Zallmann, R. Kostrica, M. Jurajda, T. Talach
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
26986. The significance of baroreflex sensitivity in hypertensive subjects with stroke
- Creator:
- Denisa Čelovská, Jozef Staško, Jozef Gonsorčík, and Diab, A.
- Format:
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, autonomní nervový systém, hypertenze, věk, autonomic nervous system, hypertension, age, baroreflex sensitivity, stroke, 14, and 612
- Language:
- English
- Description:
- The relationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf) in hypertensives with stroke in comparison with a group of stroke-free patients was evaluated. Twenty-six patients (aged 66±10 years, 11 females/ 15 males) with a history of the first ever ischemic stroke (6 months and more after stroke onset), which was neuroradiologically confirmed, were studied. These were compared to 30 hypertensive patients without history of any cardiovascular event, being of similar age and sex. BRS and BRSf were determined by the sequence and spectral methods (fiveminute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). A significant negative correlation between spontaneous BRS and blood pressure (BP) represented by the grade of hypertension was present (r = -0.52, p<0.001). Differences between hypertensives with and without stroke were detected in BRS obtained by the spectral method (BRS spect p=0.0237, BRSf spect p=0.0285) or BRS obtained by sequence method (BRS seq p=0.0532, BRSf seq p=0.0273). The greatest decline in BRS values was in hypertensive stroke patients with metabolic syndrome, who had BRS values below 3 ms/mm Hg. We found out that BRS and BRSf were more impaired in stroke patients with essential hypertension even 6 months and more after stroke onset than in stroke-free hypertensive patients. This finding was independent of age-dependent decrease of BRS. Examination of baroreflex sensitivity as a marker of autonomic dysfunction along with global cardiovascular risk stratification of individuals seems to be a method for identifying patients at high residual cardiovascular risk., D. Čelovská ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
26987. The significance of soil moisture in forecasting characteristics of flood events: A statistical analysis in two nested catchments
- Creator:
- Chifflard, Peter, Kranl, Julius, zur Strassen, Georg, and Zepp, Harald
- Type:
- article, model:article, and TEXT
- Subject:
- soil moisture, runoff prediction, catchment hydrology, spatial-temporal variability, and multivariate statistics
- Language:
- Slovak
- Description:
- We examine the feasibility and added value of upscaling point data of soil moisture from a small- to a mesoscale catchment for the purpose of single-event flood prediction. We test the hypothesis that in a given catchment, the present soil moisture status is a key factor governing peak discharge, flow volume and flood duration. Multiple regression analyses of rainfall, pre-event discharge, single point soil moisture profiles from representative locations and peak discharge, discharge duration, discharge volume are discussed. The soil moisture profiles are selected along a convergent slope connected to the groundwater in flood plain within the small-scale catchment Husten (2.6 km²), which is a headwater catchment of the larger Hüppcherhammer catchment (47.2 km², Germany). Results show that the number of explanatory variables in the regression models is higher in summer (up to 8 variables) than in winter (up to 3 variables) and higher in the meso-scale catchment than in the small-scale catchment (up to 2 variables). Soil moisture data from selected key locations in the small catchment improves the quality of regression models established for the meso-scale catchment. For the different target variables peak discharge, discharge duration and discharge volume the adding of the soil moisture from the flood plain and the lower slope as explanatory variable improves the quality of the regression model by 15%, 20% and 10%, respectively, especially during the summer season. In the winter season the improvement is smaller (up to 6%) and the regression models mainly include rainfall characteristics as explanatory variables. The appearance of the soil moisture variables in the stepwise regression indicates their varying importance, depending on which characteristics of the discharge are focused on. Thus, we conclude that point data for soil moisture in functional landscape elements describe the catchments’ initial conditions very well and may yield valuable information for flood prediction and warning systems.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
26988. The situation of social housing in Switzerland
- Creator:
- Glaser, Marie
- Type:
- article, model:article, and TEXT
- Subject:
- comparative housing policy, social housing, housing and urban sustainability, and not-for-profit housing cooperatives
- Language:
- English
- Description:
- Without a national or cantonal policy for the provision of affordable, so-called social housing, Switzerland`s way is unique in Europe. Finding appropriate housing is left to the people themselves. The challenge of building sustainable communities in urban centres in Switzerland has to address the tight housing market due to economic growth, immigration, and the renewed attractiveness of urban living. In the absence of a national low-cost housing policy, every growing city thus has to design its own strategies and implement local policies and programmes in order to counteract such developments. The role of housing cooperatives is important now and in the future. The paper gives an overview on the Swiss situation after the GFC and discusses the successful strategies of the provision and protection of affordable housing in the major city of Zurich.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
26989. The skin remodeling in type 1 diabetes and insulin resistance animal models
- Creator:
- Knaś, M., Wolosik, K., Zalewska, A., Mikucka-Niczyporuk, A., Kasacka, I., and Niczyporuk, M.
- Format:
- print, bez média, and svazek
- Type:
- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, diabetes mellitus, inzulinová rezistence, inzulin, insulin resistance, insulin, type 1 diabetes, metformin, 14, and 612
- Language:
- English
- Description:
- The skin matrix metalloproteinase 3, tissue inhibitors of matrix metalloproteinase 2 and collagen III content changes in type 1 diabetes and insulin resistance treated with insulin a nd metformin were studied. Healthy adult male Wistar rats were obtained from experimental animal house, Department of Experimental Pharmacology, Medical University in Bialystok. The rats were divided randomly into five groups of 8 rats each. Control rats were injected intraperitoneally by NaCl. Type IDDM was induced by a single injection of Streptozocin. Insulin resistance was induced by a high -fat diet. The chosen groups of rats were also treated with insulin or metformin. ELISA K its (USCN Life Science, China) were used to measure content of matrix metallo - proteinase 3 (ELISA Kit for Matrix Metalloproteinase 3 - MMP3), tissue inhibitor of matrix metalloproteinase 2 (ELISA Kit for Tissue Inhibitors of Metalloproteinase 2 - TIMP2) and content of collagen type 3 (ELISA Kit for Collagen Type III - COL3). The results were reported as a median. The statistical significance was defined as p<0.05. Type 1 diabetes and insulin resistance have significantly reduced the quality of the skin, shown by the increase in cont ent of matrix metalloproteinase 3 and the decrease in content of tissue inhibitors of matrix metalloproteinase 2. Type 1 diabetes and insulin resistance have reduced the quality of the skin expressed by type III collagen content decrease but for future studies it is recommend to determine rat interstitial collagenase, MMP -13, as well. Insulin and metformin treatment improved the quality of the diabetic skin, demonstrated by the type III collagen content increase., M. Knaś, K. Wołosik, A. Zalewska, A. Mikucka-Niczyporuk, I. Kasacka, M. Niczyporuk., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
26990. The social homeownership model – the case of Norway
- Creator:
- Sandlie, Hans Christian and Gulbrandsen, Lars
- Type:
- article, model:article, and TEXT
- Subject:
- home ownership, public housing, the Global Financial Crisis, and Norway
- Language:
- English
- Description:
- This article gives a brief overview of recent developments in Norwegian social housing emphasizing the years after the global financial crisis (GFC). In Norway, mass homeownership has been an important part of social housing in the post-war period. The GFC led to a more rigorous housing finance system, which in turn affected the possibilities of young adults entering homeownership. Nevertheless, the share of young homeowners has been stable or even growing in recent years. Today, social housing mainly refers to a rather marginal system providing housing for the most vulnerable groups.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public