Title: Influence of modified games on the quantity of game combinations of primary school age floorball players Objectives: The aim of this work was to find out the effect of prepared training programme on quantity of passing, team cooperation and quantity of shots. The research was aimed on passing accuracy (passing quality) after ball carrying, quantity of passes in training match on smaller pitch. The number of the players was 3 on 3 there. It was also aimed on quantity of passes in league match on standard pitch. There were 5 players against 5. At the end of the training programme, we made revisory tests to assess a positive effect of the programme. Methods: We used a method of an experiment. At first, there were preliminary tests before an adjusted training program so that we got input data. Then we applied adjusted training programme and then there were another control tests to get output data. The programme included both modified games and game-like drills. During the tests, we used participant observation. Results: The results showed an increase of quantity in all tests. But only in passing accuracy after ball carrying test and in quantity of passes in league match the results were statistically significant. The other test showed no statistical significance. Keywords: game, modification,...

The information retrieval (IR) field has been successful in developing techniques to address many types of information needs. However, there are cases in which traditional approaches to IR are not able to produce adequate results. Examples include: when a small set of (2-3) documents is needed as an answer rather than a single document, or when "query splitting" is required to satisfactorily explore the document space. We explore an alternative model of building and presenting retrieval results for such cases. In particular, we research effective methods for handling information needs that may: 1. Include multiple topics: A typical query is interpreted by current IR systems as a request to retrieve documents that each discusses all topics included in that query. We propose an alternative interpretation based on query splitting. It allows queries to be interpreted as requests to retrieve sets of documents rather than individual documents, with meaningful relationships among the members of each such set. 2. Be interpreted as parts in a chain of relationships: Suppose a query concerns topics t1 and tm. Is there a relation between topics t1 and tm that involves t2 and possibly other topics as in {t1, t2, â ¦ tm}? Thus, we propose an alternative interpretation of user queries and presentation of the results. Our interpretation has the potential to improve retrieval results whenever there is a mismatch between the user's understanding of the collection and the actual collection content. We define and refine a retrieval scheme that enhances retrieval through a framework that combines multiple sources of evidence. Query results in our interpretation are networks of document groups representing topics, each group relating to and connecting to other groups in the network that partially answer the user's information need. We devise new and more effective representations and techniques to visualize results, and incorporate the user as part of the retrieval process. We also evaluate the improvement of the query results based on multiple measures. In particular, we verify the validity of our approach through a study involving a collection of Operating Systems research papers that was specially built for this dissertation. / Ph. D.

The identity of the long-overlooked Ronabea morindoides and Patabea tenuiflora, synonymous with a species of Appunia (Rubiaceae). Candollea 76: 83-92. In English, English abstract. The identity of Ronabea morindoides A. Rich. has long been unclear and is here investigated. Two sheets of original material corresponding to this name are deposited in the General Herbarium of the National Museum of Natural History of Paris (P), and represent a mixed collection; one part of this material corresponds better with the description of this taxon and is more unambiguously identifiable, and is here designated the lectotype. With this typification, Ronabea morindoides represents a species of Appunia Hook. f. The identity of Patabea tenuiflora DC. has also remained uncertain since its description and is here clarified by studying the holotype in the Candolle Herbarium (G-DC); this is an additional synonym of R. morindoides. Taxonomic review of this group in the Guianas also finds that Ronabea morindoides is an older name for Appunia brachycalyx (Bremek.) Steyerm. and Appunia surinamensis Bremek. (Morindeae). Therefore, the new combination Appunia morindoides (A. Rich.) Delprete, C.M. Taylor & T. McDowell is here published. Received: August 15, 2020; Accepted: December 1, 2020; First published online: February 1, 2021

Thesis ((M. Pharm. (Pharmaceutics)) -- University of Limpopo, 2019 / Epilepsy is the fourth most common neurological disorder after migraine, stroke and Alzheimer’s disease and it affects about fifty million people worldwide. Careful consideration should be taken when deciding to initiate treatment in epilepsy as it should consider the balance between the possibility of further seizures and their associated risks, including the possible risk of sudden expected death, inconvenience and the risks of taking regular medication for each individual. In the early 1980’s, the first-line treatment for epilepsy was polytherapy. This was due to findings that smaller doses of two drugs rather than larger doses of one drug can achieve synergistic effects or less drug toxicity. However, following more trials on the treatment of epilepsy, this was later changed to monotherapy as first-line treatment. Despite the change, patients remain uncontrolled on a single anti-epileptic drug, thus they are initiated on polytherapy, one such combination being carbamazepine in combination with sodium valproate. The use of these in combination has pharmacological threats such as compliance, the control of side effects and the achievement of synergistic effects. The development of a Fixed Dose Combination (FDC) has often been used to resolve pharmacological threats, and this study aims to develop a fixed dose combination tablet of carbamazepine and sodium valproate to resolve the pharmacological threats in epilepsy. Samples of carbamazepine and sodium valproate and a physical mixture (1:1 w/w) of both drugs and excipients were prepared for compatibility with thermal analysis and spectroscopy techniques. Data was analysed by comparing the DSC curves, FTIR spectra, XRPD peaks and TAM analysis of carbamazepine and sodium valproate alone and in their physical mixture (1:1 w/w) and with excipients. Both carbamazepine and sodium valproate were evaluated for flowability using angle of repose, tapped and bulk density, compressibility index and particle size distribution. To formulate the proposed FDC tablet of carbamazepine and sodium valproate, direct compression and wet granulation methods were employed. The tablets were then evaluated for official and non-official post formulation parameters (weight variation, crushing strength, friability, diameter and thickness, and disintegration) according to BP and USP standards. A standardised HPLC method was developed and validated for analytical procedures. Dissolution studies were conducted xiii according to USP methods to verify and quantify the release of the APIs from the FDC tablet. Carbamazepine and sodium valproate were tested for compatibility with excipients using DSC, FTIR, XRPD and TAM analysis. The overall results confirmed that carbamazepine and sodium valproate are compatible, with each other and the excipients used in the study. Powder flow of carbamazepine and sodium valproate was poor, hence they were subjected to granulation prior to compression to improve flowability. The specifications of the fixed-dose combination were developed in accordance with the FDA’s quality by design concept and WHO recommendations. The tablets were subjected to non-official and official pharmacopoeial tests, and passed all the tests. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the fixed-dose combination. The initial dissolution rate (DRi) of carbamazepine and sodium valproate in the SLS dissolution medium was rapid as required for an immediate release formulation. The study aimed at developing a fixed dose combination of carbamazepine and sodium valproate to try to reduce the burden of taking more than one tablet for epilepsy. Based on the results obtained from preformulation studies to assay of the final product, the study was successful. / Chieta bursary and HWseta

South Africa has the largest HIV-infected population in the world, with 2015 estimates of 7 million people living with HIV and 180,000 AIDS-related deaths. The South African government began scale-up of a public-sector HIV care and treatment program in 2004, and by the end of 2015, 3.4 million HIV-infected individuals were on antiretroviral therapy (ART). When scale-up began in South Africa, ART was only available to HIV-infected individuals with CD4 counts ≤200 cells/µL or WHO clinical stage 4 disease. In 2010, treatment was extended to patients who were pregnant or who had tuberculosis and a CD4 ≤350 cells/µL, and in 2011, eligibility was extended to all patients with CD4 ≤350 cells/µL. In 2013 patients with WHO clinical stage 3 disease became eligible. In 2015, the eligibility threshold was increased to CD4 ≤500 cells/µL, and in 2016, the South African National Department of Health announced that the country would implement a “test and treat” strategy, offering free ART to all HIV-infected individuals, regardless of CD4 count. This dissertation examines the effectiveness of several expansions and modifications to South Africa’s treatment program. In study 1, we investigated whether the 2011 extension of HIV treatment to patients with CD4 counts ≤350 cells/µL successfully increased the number of newly-eligible patients on treatment (those with CD4 counts between 201–350 cells/µL) without crowding out previously-eligible patients with more severe disease (CD4 counts ≤200 cells/µL), focusing on a network of rural clinics in KwaZulu-Natal. We found encouraging results, with newly-eligible patients (CD4 201–350) initiating treatment at a greater frequency (73.0 additional patients per month; 95% CI: 42.1; 103.9) and 47% faster than before (95% CI: 19%; 82%), while previously eligible patients (CD4 ≤200) experienced no decline in the number of patients initiating treatment or the speed of treatment uptake. In study 2, we evaluated whether the introduction of a single-pill fixed-dose combination (FDC) treatment for ART initiators in South Africa had an impact on attrition from care compared to the previously-recommended multiple-pill regimen. We focused on an urban clinic in Johannesburg, using four different clinic attendance measures to define attrition (generally a combined measure of loss to follow-up and mortality). An intention-to-treat analysis revealed an estimated 11.3 percentage point decrease in attrition (95% CI: -22.0; -0.6) associated with the policy change, while a regression discontinuity analysis estimated an 18.0 percentage point drop in attrition (95% CI: -33.6; -2.4) associated with single-pill FDC treatment relative to multiple pills, controlling for unmeasured confounding. In study 3, we used stratified instrumental variable analysis to examine whether the effect of FDCs on attrition varied across subsets of the patient population in the same Johannesburg clinic we evaluated in study 2. We saw larger effects among women (RD -0.25; 95% CI: -0.42; -0.09), non-anemic patients (RD -0.24; 95% CI: -0.41; -0.08), patients with early-stage (as opposed to advanced) clinical disease (RD -0.20; 95% CI: -0.32; -0.07), and those with high CD4 counts (for CD4 ≥350 cells/µL, RD -0.58; 95% CI: -1.58; 0.42). These results suggest that healthier patients saw the greatest improvement in retention in care following the switch from multiple-pill to single-pill regimens. In an era where the healthiest HIV-infected patients are now being targeted for ART treatment, FDCs can play a large role in preventing attrition from care. These three studies depict an HIV program that has successfully grown to treat increasing numbers of patients using up-to-date strategies of care. Given the immense scale and cost of South Africa’s HIV treatment program, it is important to continue to monitor its effectiveness, especially as it introduces new treatments and strategies and adapts to the changing epidemic.

Decreasing the impact of stressors on the body remains an important area of study for the affected population. While there is evidence showing that cognitive behavior therapy (CBT), a psychotherapy approach, results in decreased stress, little was found about the effects of chiropractic treatment (CC) on stress. The purpose of this quantitative archival study was to determine whether the combination therapy of CC and CBT was more effective in decreasing stress than CBT independently. Cognitive neuropsychology served as the theoretical lens. Client data from a mental health and chiropractic care center on the West coast (N = 112) were divided into 2 treatment groups, CBT and CC and CBT alone. Pre and posttreatment data were collected on stress, anxiety, and nerve conduction. ANOVA test results indicated that there were no statistically significant differences in the mean change scores between the 2 groups in terms of individual participants' stress, anxiety, and nerve interference. Although there was no significant interaction effect, results showed that both the combination therapy and CBT alone led to a decrease in stress and anxiety and an increase in the nerve conduction of participant's posttreatment. While this archival study did not yield evidence of the benefits of CC for stress-related disorders, its results suggest that future researchers should pursue more direct efforts to evaluate the effects of combination therapies. Considering the high number of people who experience stress-related challenges, the incorporation of CC along with a psychological treatment might engender positive social change for individuals and healthcare practitioners through the potential reduction of stress.

Comparative performance of the electronic, conventional, and combination (electronic and conventional) ovens was studied in the preparation of five typical foods: baked custard, lemon cake, baked potatoes, orange marmalade tea loaf, and roast chicken. The data collected included final temperature of each food and ratings of each food by a taste panel. Foods prepared electronically and by the combination method required significantly less time with the exception of lemon cake. Foods prepared by the combination and conventional methods were preferred by the taste panel over foods prepared electronically with the exception of custard which was rated superior to custard cooked conventionally.

Les sources lasers femtosecondes sont utilisées dans grand nombre d’applications (industrielles, médicales, de recherche fondamentale) avec un besoin croissant d’impulsions très énergétiques à haut taux de répétition. Bien que la technologie Ti:Saphir fournisse des impulsions PetaWatt, son taux de répétition s’avère limité. Une alternative est l’utilisation de la technologie fibrée. Cependant, l’énergie extractible d’une seule fibre est intrinsèquement limitée.Une solution prometteuse est alors de réaliser une combinaison de fibres (jusqu’à plus de 10 000 fibres pour l’accélération de particules). La combinaison de fibres par méthode interférométrique (avec un record de 64 fibres combinées en régime continu) a prouvé qu’elle était un excellent candidat pour la combinaison d’un grand nombre de fibres.La collaboration XCAN entre l’Ecole Polytechnique et Thales, vise à réaliser un démonstrateur de combinaison cohérente de 61 fibres amplifiées en régime femtoseconde. Les travaux menés au cours de cette thèse s’inscrivent dans ce projet.Dans un premier temps, afin d’étudier les points durs inhérents au régime femtoseconde tout en s’affranchissant des difficultés liées à l’amplification, la méthode interférométique en régime femtoseconde a été étudiée sur un démonstrateur passif, c’est-à-dire sans amplification, de 19 fibres. Une fois la méthode de mise en phase validée celle-ci a pu être testée avec succès sur le démonstrateur avec amplification du projet XCAN.Nous présentons également les travaux menés afin d’augmenter un paramètre clé des systèmes de combinaison de faisceaux à savoir : l’efficacité de combinaison du système laser. Pour cela, nous avons réalisé une mise en forme de faisceaux issus des fibres de la tête optique. Cette mise en forme, gaussien vers super-gaussien, est réalisée à l’aide de deux réseaux de lames de phase dont nous présenterons le calcul des profils asphériques. Afin de valider expérimentalement nos simulations et après réalisation des lames de phase nous avons pu tester celles-ci sur le démonstrateur passif, démontrant une augmentation de 14 %.Les travaux présentés dans ce manuscrit présentent ainsi les premiers par vers la réalisation d’une nouvelle architecture laser massivement parallèle, capable de délivrer à la fois une haute puissance crête et une haute puissance moyenne. / Femtosecond fiber sources are used in a large number of applications (industrial, medical, fundamental physics) with a growing need in high energy pulses at high repetion rate. Although Ti: Saphirre technology provides energies up to PetaWatt, its repetion rate is low (up to 1 Hz). An alternative is to use an amplified fiber. However, the extractable energy of a single fiber is intrinsically limited.A solution is then to combine several fibers (up to 10 000 fibers for particle acceleration). Coherent beam combining of fibers with an interferometric method (with a record of 64 fibers combined in the cw regime) has proven to be an excellent candidate to combine a large number of fibers.The XCAN project, a collaboration between l'Ecole polytechnique and Thales, aims to realize a demonstrator of 61 fibers coherently combined in the femtosecond regime.The works presented in this thesis are part of this project.In order to study the hard points inherent to the femtosecond regime and to free from the amplification issues, the interferometric method has been implemented on a passive demonstrator, meaning without amplification, of 19 fibers. Once the interferometric method validated, it has been succesfully tested on the amplified XCAN demonstrator.We present also the works done to increase a key parameter of beam combining systems : the combining efficiency. To do this, we have realized a beam shaping of the fiber array output beams. This beam shaping, gaussian to super-gaussian, is done with two arrays of phase plates. The aspherical profiles calculation is described. In order to validate our simulations we have tested the phase plates on the passive demonstrator by getting an increase of 14 %.The works presented in this manuscript are the first steps towards a new massively parallel laser architecture, able to provide both high peak power and high average power.

Indiana University-Purdue University Indianapolis (IUPUI) / Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly disease characterized by aggressive metastasis and therapeutic resistance. Reactive stroma in pancreatic tumors contributes to tumor signaling, fibrosis, inflammation, and hypoxia. Hypoxia signaling creates a more aggressive phenotype with increased potential for metastasis and decreased therapeutic efficacy. Carbonic anhydrase IX (CA9) functions as part of the cellular response to hypoxia by regulating intracellular pH to promote cell survival. Apurinic/Apyrimidinic Endonuclease-1-Reduction/oxidation Effector Factor 1 (APE1/Ref-1) is a multi-functional protein with two major activities: endonuclease activity in DNA base excision repair and a redox signaling activity that reduces oxidized transcription factors, enabling them to bind target sequences in DNA. APE1/Ref-1 is a central node in redox signaling, contributing to the activation of transcription factors involved in tumor survival, growth, and hypoxia signaling. This work evaluates the mechanisms underlying PDAC cell responses to hypoxia and APE1/Ref-1 redox signaling control of hypoxia inducible factor 1 alpha (HIF1a), a critical factor in hypoxia-induced CA9 transcription. We hypothesized that obstructing the HIF-CA9 axis at two points via APE1/Ref-1 inhibition and CA9 inhibition results in enhanced PDAC cell killing under hypoxic conditions. We found that HIF1a-mediated induction of CA9 is significantly attenuated following APE1/Ref-1 knock-down or redox signaling inhibition in patient-derived PDAC cells and pancreatic cancer-associated fibroblast cells. Additionally, dual-targeting of APE1/Ref-1 redox signaling activity and CA9 activity results in enhanced acidification and cytotoxicity of PDAC cells under hypoxic conditions as well as decreased tumor growth in an ex-vivo 3-dimensional tumor co-culture model. Further experiments characterized novel analogs of clinically relevant drugs targeting the key enzymes in this pathway, resulting in improved potency. These results underscore the notion that combination therapy is essential and demonstrate the potential clinical utility of blocking APE1/Ref-1 and CA9 function for novel PDAC therapeutic treatment.

IUPUI / Fatty acid synthase (FASN) over-expression has been associated with poor prognosis and recurrence in cancer patients. In addition, it has also been found that overexpression of FASN causes resistance to DNA-damaging treatments by up-regulating the non-homologous end joining (NHEJ) repair of DNA double-strand break. Proton pump inhibitors (PPIs), were originally designed to decrease gastric acid production by binding irreversibly with gastric hydrogen potassium ATPase. PPIs have recently been reported to reduce drug resistance in cancer cells when used in combination with other chemotherapeutics, although the mechanism of resistance reduction is uncertain. In our lab, previous investigation showed that PPIs decreased FASN thioesterase (TE) domain activity and cancer cell proliferation in a dose-dependent manner. In this study, I tested the hypothesis that PPIs sensitize breast cancer cells to doxorubicin and ionizing radiation (IR) treatments by inhibiting FASN. When administered to breast cancer cells as single-agent, lansoprazole exhibited the highest potency in inhibiting both FASN activity and breast cancer cell proliferation, among four PPIs tested. In addition, treatment of breast cancer cells with lansoprazole decreased the mRNA and protein levels of poly (ADP-ribose) polymerase-1 (PARP-1) and NHEJ activity, accompanied by elevated γ-H2AX expression. Following a 3-day treatment with lansoprazole, a dose-dependent disruption in cell cycle disruption and increased apoptosis were also detected. Combination of lansoprazole with either doxorubicin or IR caused profoundly higher levels of DNA damage accumulation than doxorubicin or IR treatment alone, suggesting synergistic effects. Taken together, our observations suggest that PPIs synergistically suppress breast cancer cells in combination with DNA damaging treatments by inhibiting FASN. These findings may provide a potential route to overcome resistance to DNA-damaging chemo/radiation treatments in refractory breast cancers.