Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib’s inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

Background: Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Methods: Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: \u3c200 cells/mm3 initiated antiretroviral therapy, and \u3e500 cells/mm3 received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin \u3c 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. Results: At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥6 months) and shorter ARV exposure. Severe an- aemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1–2 months of ARV’s, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Conclusions: Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring

Genetic interactions between a phospholipase A2 and the Rim101 pathway components in S. cerevisiae reveal a role for this pathway in response to changes in membrane composition and shape

Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A2 (PLA2s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA2 in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA2 activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA2 activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them

IMP(2)ART systematic review of education for healthcare professionals implementing supported self-management for asthma

Abstract Despite a robust evidence base for its effectiveness, implementation of supported self-management for asthma is suboptimal. Professional education is an implementation strategy with proven effectiveness, though the specific features linked with effectiveness are often unclear. We performed a systematic review of randomised controlled trials and controlled clinical trials (published from 1990 and updated to May 2017 using forward citation searching) to determine the effectiveness of professional education on asthma self-management support and identify features of effective initiatives. Primary outcomes reflected professional behaviour change (provision of asthma action plans) and patient outcomes (asthma control; unscheduled care). Data were coded using the Effective Practice and Organisation of Care Taxonomy, the Theoretical Domains Framework (TDF), and Bloom’s Taxonomy and synthesised narratively. Of 15,637 articles identified, 18 (reporting 15 studies including 21 educational initiatives) met inclusion criteria. Risk of bias was high for five studies, and unclear for 10. Three of 6 initiatives improved action plan provision; 1/2 improved asthma control; and 2/7 reduced unscheduled care. Compared to ineffective initiatives, effective initiatives were more often coded as being guideline-based; involving local opinion leaders; including inter-professional education; and addressing the TDF domains ‘social influences’; ‘environmental context and resources’; ‘behavioural regulation’; ‘beliefs about consequences’; and ‘social/professional role and identity’. Findings should be interpreted cautiously as many strategies were specified infrequently. However, identified features warrant further investigation as part of implementation strategies aiming to improve the provision of supported self-management for asthma

Online media content retrieval and analysis

Diplomska naloga z naslovom Izdelava orodja za shranjevanje in analizo spletnih medijskih vsebin je bila zastavljena s ciljem implementacije hitrega in sistematičnega preučevanja javnih medijskih vsebin. V diplomski nalogi smo si zadali sledeče cilje: ustvariti program za pridobivanje spletnih vsebinvzpostaviti povezavo med omenjenim programom in strežnikom za shranjevanje podatkovbeležiti in analizirati pridobljeno vsebino. Naš začetni program za pridobivanje vsebin smo implementirali v programskem jeziku Java. Sprva smo se želeli posvetiti analizi slovenskih besedil, vendar smo se zaradi težav pri implementaciji preusmerili na angleški jezik. Uporabili smo NLP (Natural Language Processing) tehnike, ki so temeljile na knjižnici Stanford CoreNLP. Podatke smo shranjevali v SQL (Structured Query Language) bazo v njihovi osnovni in lematizirani obliki, pri čemer smo pridobljene vsebine razdelili na več sklopov. Temu je sledila analiza s pomočjo specifično zastavljenih funkcij. V glavnem delu analize smo se ukvarjali s testiranjem hitrosti poizvedovanja glede na uporabljeno metodo. Začeli smo z enostavnimi klici na celotni bazi, nadaljevali z uporabo pogledov, kasneje pa dodali še indekse. Rezultati so bili skladni s pričakovanji. Uporaba pogledov in indeksov je znatno skrajšala čas poizvedb.The thesis was conceived with the idea of implementing a fast and systematic way of analysing media coverage, namely web articles. The main focus of the thesis addresses: the implementation of a program for obtaining web contentbridging said program with a server for data storagetracking and analysing the obtained data. Our starter program was implemented in Java. At the beginning, we wanted to focus on data in Slovene, but due to problems with the implementation of a working analyser, we shifted our focus to English. Using Stanford CoreNLP, we utilized various NLP (Natural Language Processing) techniques. The data was restructured to its most basic form using lemmatization and then stored in a SQL (Structured Query Language) server. What followed were experiments on said data using specific functions for specific subgroups. The main focus of the analysis was testing the speed of querying based on different factors. The first step used just a normally written query. The second step was focused on views, and the last optimization included the use of indexing. As predicted, the runtime significantly decreased with each additional step

The assessment of maturity model of business intelligence in Slovenian railways

The effective use of business intelligence represents not only a challenge for a company but also potentially big benefits which are hard to prove. There are maturity models which help us understand how to take advantage of our investments into business intelligence and proceed to another level of maturity. Maturity models help companies understand their current position and possible improvements that can be made. It also helps the company to adapt business and informatization better. One of these models is also TDWI maturity model which refers mostly to the technological aspect of maturity. The system of business intelligence needs to be improved and expanded constantly. It is vital that we understand the realization of the system of business intelligence as a project which is never completed. With the additional use of business intelligence tehnology we also progress to a higher level in the maturity model which results in additional business value for a company. The first part of the thesis refers mostly to a general description of business intelligence. The second part discusses business intelligence and informatization in the company Slovenske železnice, d.o.o.. The third part shows the results of the research which was conducted with the aim to evaluate the level of business intelligence in this company. In the end, I give a suggestion for the improvement based on the results of the research, in which two business intelligence tools were compared with the use of defined criteria

Visual inspection, tests and measurements of electrical installations

Dandanes si sveta brez elektrike in s tem električnih inštalacij, ki se nahajajo že praktično povsod, preprosto ne moremo več predstavljati. Zato je uvedba ustreznih standardov in predpisov, ki jih je potrebno spoštovati in ki se vseskozi posodabljajo in zaostrujejo, nujna, da se zagotovi prepotreben nadzor na področju električnih inštalacij. Potrebno je poudariti pomembnost preizkušanja varnosti električnih inštalacij in dela preglednika. S tem se zagotovi standardizacija in predvsem varnost uporabnikov, kot tudi objektov samih. V sledečem diplomskem delu želimo bralcu predstaviti ustrezno teoretično ozadje s področja nizkonapetostnih električnih inštalacij, odgovore in predloge kako ustrezno pregledati, izmeriti in preizkusiti posamezne dele inštalacije. Poleg teoretičnega dela, se bralcu na koncu predstavi konkreten praktični primer z izgledom končnega poročila, ki je narejen po ustreznem protokolu in dodatkom za študente.Nowadays, we simply cannot imagine the world without electricity and electrical installations, which are already practically everywhere. Therefore, the introduction of appropriate standards and regulations that needs to be adhered to, constantly updated and exacerbated, is necessary in order to provide much needed control in the field of electrical installations. It is necessary to emphasize the importance of testing the safety of electrical installations and the work of the controller. This ensures standardization and, above all, the safety of users as well as the facilities themselves. In the graduation work, we want to present to the reader theoretical background from the field of low voltage electrical installations, answers and suggestions on how to properly inspect, measure and test individual parts of the installation. In addition to the theoretical work, the reader is finally presented a concrete practical example with the appearance of the final report, which is made according to the appropriate protocol and additonal part for students