Concurrent thermochemoradiotherapy for brain high-grade glioma

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas

Predictive and prognostic significance of mRNA expression and DNA copies aberrations of ERCC1, RRM1, TOP1, TOP2A, TUBB3, TYMS, and GSTP1 genes in patients with breast cancer

Increasingly, many researchers are focusing on the sensitivity in breast tumors (BC) to certain chemotherapy drugs and have personalized their research based on the assessment of this sensitivity. One such personalized approach is to assess the chemotherapy’s gene expression, as well as aberrations in the number of DNA copies—deletions and amplifications with the ability to have a significant effect on the gene’s activity. Thus, the aim of this work was to study the predictive and prognostic significance of the expression and chromosomal aberrations of eight chemosensitivity genes in breast cancer patients. Material and methods. The study involved 97 patients with luminal B breast cancer IIB–IIIB stages. DNA and RNA were isolated from samples of tumor tissue before and after treatment. Microarray analysis was performed for all samples on high-density microarrays (DNA chips) of Affymetrix (USA) CytoScanTM HD Array and Clariom™ S Assay, human. Detection of expression level of seven chemosensitivity genes—RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1—was performed using PCR real-time (RT-qPCR). Results. The expression of the RRM1 (AC scheme), TOP2a, TYMS, and TUBB3 genes in patients with an objective response to treatment (complete and partial regression) is higher than in patients with stabilization and progression (p < 0.05). According to our results, the presence of a high level of GSTP1 in a tumor biopsy is associated with the low efficiency of the NAC CP scheme (p = 0.05). The presence of RRM1 deletion is associated with complete and partial regression, as for the TOP1 and TUBB3 genes (p < 0.05). Higher rates of metastatic survival are associated with a high level of expression and amplification of the GSTP1 gene (log-rank test p = 0.02 and p = 0.05). Conclusion. Thus, a complex assessment of the chemotherapy’s gene expression is important not only for understanding the heterogeneity and molecular biology of breast cancer but also to obtain a more accurate disease prognosis

Effect of early-stage human breast carcinoma on monocyte programming

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Process analysis of the selected bank process

Bakalářská práce je zaměřena na procesní analýzu a optimalizaci procesu podporujícího fungování informačního managementu v bance. Práce je rozdělena do dvou částí. V teoretické části jsou popsány důležité pojmy a nástroje použité v praktické části práce. Poté následuje praktická část, která se zabývá procesní analýzou a optimalizací vybraného procesu banky. Zde je na začátku uveden obecný popis společnosti a útvaru Informační management, ve kterém analyzovaný proces působí. Dále se praktická část zaměřuje na analýzu současného stavu vybraného procesu, jeho zmapovaní modelovací metodikou BPMN, vyhodnocení za pomoci sestavení SWOT analýzy, rozebrání problémových oblastí procesu a navržení případných zlepšení pro odstranění problémů.The focal point of the thesis is the process analysis and the optimization of the supporting functions of information management in the bank. In the theoretical part, there is a description of the important terms and definition of the concepts as well as the tools which have been used in the practical part of the thesis. The practical part deals with the process analysis and the optimization of the selected bank process. This also includes a general description of the company and the Information Management department in which the analyzed process works. The study then focuses on the analysis of the current status of the selected information management process and its mapping with the BPMN modeling methodology. The subsequent evaluation uses SWOT analysis to identify the problem areas of this process and offers recommendations for possible improvements to solve these problems

Critical Measures and Parameter Space of Jenkins-Strebel Quadratic Differentials

The thesis is devoted to applications of the theory of quadratic differentials to the problems of construction of critical measures, that provide critical values of the logarithmic energy of a charge system on the complex plane. We observe the properties of supports of such measures. We consider the problem of describing parameter space of Jenkins-Strebel differentials, which is related to the problem of describing critical measures

UX practices in the design process of mobile application

Cílem této diplomové práce je návrh a tvorba digitálního prototypu mobilní aplikace pro podporu vyhledávání sportovních aktivit zohledňující postupy User Experience. Práce se zaměřuje na teoretický rozbor a sjednocení pojmů User Experience Design (UXD) a oblastí souvisejících s jeho tvorbou. Jsou zde popsané základní přístupy k tvorbě UXD, jeho začlenění do cyklu vývoje softwaru a seznámení se s technikami, které lze ve fázích vývoje využít. Dále se práce zaměřuje na představení digitálního prototypu, jeho pozici v životním cyklu softwaru a na popis základních heuristik a principů, které jsou základem pro jeho návrh. V rámci práce je následně proveden návrh a tvorba digitálního prototypu se zřetelem na pravidla vymezená v teoretické části. Výsledkem práce je navržený a řádně otestovaný digitální prototyp mobilní aplikace.The main goal of this master's thesis is to design and create the digital prototype of the mobile application focused on searching for sport activities using the User Experience (UX) practices. This thesis provides the information about the User Experience Design (UXD) and related topics. The thesis describes the basic approach to the UXD, its integration into a software development lifecycle and introduces techniques that can be used in the development phases. Subsequently, this thesis focuses on the representation of the digital prototype and its position in the software development lifecycle. Furthermore, the thesis describes basic heuristics and principles that are essential for designing a digital prototype. As part of the thesis author designs and creates the digital prototype based on the information described in the theoretical part. The final result of the thesis is a designed and properly tested digital prototype of the mobile application

Analytical, combinatorial and topological properties of quadratic differentials and their applications

Quadratic differentials first appeared in 1930s in works of Teichmuller in connection with moduli problem for Riemann surfaces. Later it was revealed that quadratic differ- entials and their trajectories give solutions to extremal problems for moduli of families of curves and extremal partition of Riemann surfaces. Over the last decades there has been discovered a connection between quadratic differentials and extremal problems of different nature related to minimal surfaces, potential theory, approximation theory, mathematical physics. In this work, we study quadratic differentials, discover new properties of certain types of quadratic differentials and explore the connection of quadratic differentials with other disciplines, such as discrete mathematics, topology and even applied math- ematics. We apply the theory of quadratic differentials to solve problems of complex analysis and study analytical problems that are connected with quadratic differentials. The dissertation is organized as follows. Chapter 1 contains an introduction to the notions and facts that are necessary for understanding the main results of this work. Section 1.1 gives a short introduction to quadratic differentials and their trajectory structure. It also recalls the definition of reduced moduli of digons. Section 1.2 de- scribes the tools from discrete mathematics and topology that are used in this work. Chapter 2 gives a summary of the research papers that constitute the main scientific contributions of the thesis. Both Chapter 1 and Chapter 2 are followed by lists of refer- ences. The following papers are included in Chapter 3. Paper A: A. Frolova, M. Levenshtein, D. Shoikhet, and A. Vasil’ev, Boundary distortion estimates for holomorphic maps, InComplex Analysis and Operator Theory, 8 (2013), no. 5, 1129–1149. Paper B: A. Frolova, A. Vasil’ev, Combinatorial description of jumps in spectral networks, accepted to Proceedings AMS. Paper C: A. Frolova, D. Khavinson, and A. Vasil’ev, Polynomial lemniscates and their fingerprints: from geometry to topology, Submitted to New Trends in Complex and Harmonic Analysis. Paper D: A. Frolova, M. Solberg, and A. Vasil’ev, Pure braids and homotopy classes of closed loops, paper in preparation. In Paper A we apply extremal partitions and moduli of digons to obtain a boundary distortion estimate for a conformal self-mapping of the unit disk with two fixed points on the boundary. Paper B studies combinatorial structure of the family of quadratic differentials with a finite simple pole that possess a short trajectory. In Paper C we discover some properties of fingerprints of polynomial lemniscates and construct a non-unitary operad that realizes a process of approximation of two dimensional shapes by polynomial lemniscates. In Paper D we define an action of a braid group on homotopy classes of closed curves on a punctured sphere, which is related to a problem of constructing an operad on quadratic differentials with several double poles