Enhancing service delivery for chronic low back pain: evidence for patient-centred physiotherapy and the objective measurement of outcome.

This thesis incorporates two studies, whose combined aims were to inform and improve the physiotherapy management of chronic low back pain (CLBP) patients in primary care. A qualitative study explored patients' perceptions of physiotherapy for CLBP, in order to influence service redesign. Twenty-five people who had received physiotherapy for CLBP were purposively sampled. They participated in semi-structured interviews that explored their physiotherapy experience. Framework analysis was conducted on the data. The findings demonstrated that CLBP patients' expectations of physiotherapy were not consistently met and that attending physiotherapy did not consistently facilitate self-management of CLBP. Activity and participation were important to CLBP patients. However, in this sample, activity limitations and participation restrictions were not consistently addressed in physiotherapy. A definition of patient-centred physiotherapy for CLBP was generated from the patients' perspective; the physiotherapy received by this sample was not consistently patient-centred by this definition. A quantitative study explored the potential for using gait and sit-to-stand (STS) analysis as objective measures, in order to enhance outcome measurement in CLBP patients. Convenience samples of 17 CLBP patients and 20 people without LBP were recruited. An optical motion analysis system was used to compare the spatial and temporal gait parameters, temporal STS parameters, and pelvic and spinal kinematic parameters of each sample. The relationship between CLBP patients' self-reported pain and disability levels and the objective measures of gait and STS was explored. The CLBP sample demonstrated statistically significant reductions in several parameters compared to the control sample: stride length and pelvic side flexion during normal gait, pelvic side flexion and spine flexion during fast gait, and peak spinal flexion during STS. An association was demonstrated between increased pain intensity and increased pelvic side flexion during fast gait. New knowledge on the physiotherapy management of CLBP emerged from this research. Methods of enhancing patient-centredness and facilitating self-management emerged from the qualitative study. The differences detected in the quantitative study suggested that measuring gait and STS might provide useful additional outcome measures for CLBP patients, in order to overcome some of the limitations of self-report measures. They might also assist with classifying and planning individually-tailored treatment approaches for CLBP patients. Although generalisation is limited by the sample sizes, the implications (for practice and education) and suggestions for further work arising from this research are important in attempts to enhance physiotherapy for CLBP

Drug development progress in duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Will e shall : uma análise de seus usos no Ingles científico e na Língua Inglesa em geral

Orientador: Otília ArnsDissertaçao (mestrado) -Universidade Federal do Paraná. Curso de Pós-Graduaçao em LetrasResumo: No presente trabalho, fez-se um estudo dos usos dos auxiliares modais WILL e SHALL baseando-se nas obras de Jespersen, Leech e Palmer. Tentou-se estabelecer os usos realmente distintos destes dois modais partindo de textos, científicos de Engenharia Mecânica, Botânica, Medicina, e de Inglês Geral. Estudados os três autores supra-citados verificou-se a necessidade de se fazer um estudo da obra mais recente de Palmer "Modality and the English Modals" (1979). Esta obra, pelas modificações propostas, apresentou melhores condições do que as anteriores para servir de modelo a esta pesquisa. Procedeu-se em seguida à coleta e análise dos dados extraídos de textos científicos e a posterior análise estatística. Para que se obtivesse uma certeza maior quanto à fidedignidade da classificação dos usos modais de WILL e SHALL aplicou-se o teste do X2 ou teste de Pearson. Concluiu-se que os usos comuns nas quatro áreas podem ser considerados como sendo características da língua, enquanto os variáveis são características da área em questão. Concluiu-se também que pelo fato dos usos modais de WILL e SHALL variarem por área, é importante o seu ensino aos alunos que utilizam textos específicos em inglês como meio de aumentarem seus conhecimentos em diversas disciplinas do seu curso de graduação.Abstract: The present study consists of an analysis of the the modal auxiliaries will and Shall based on the studies carried out by Otto Jespersen, Geoffrey Leech and F. R. Palmer. The identification of the distinct uses of these two modal auxiliaries in texts of Mechanical Engineering, Botany, Medicine and General English was the main aim of this research. After studying the subject according to the three authors mentioned above, it proved to be necessary to review a more recent study on this theme provided by F. R. Palmer in his book "Modality and the English Modals" (1979). The modifications proposed by the author were to be the framework adopted in this research. The collection of data and the statystical analysis were made; and the X2 test or Pearson's test was applied to get a more accurate analysis. The results showed that the common uses in the four areas studied can be considered as characteristics of the language in general whereas the variables are characteristics of the studied areas. This research also showed that as the uses of the auxiliary modals Will and Shall vary according to the areas, the teaching of these uses is important to the students that need reading specific texts in English as a means of learning their own major subjects