Yes / Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. PROSPERO database (CRD42018108536). / This work presents research funded by the Pharmacy Research UK (grant reference: PRUK-2018-GA-1-KM) and Leeds Teaching Hospitals NHS Trust.

This study examined the relationship between selective serotonin reuptake inhibitor (SSRI) medication and auditory measures in clinically depressed women. Experimental subjects were tested in both a medicated and unmedicated condition. Experimental subjects were compared to a normal control group; additionally intrasubject comparison was made within the experimental group. Test measures included: audiometry, tympanometry, otoacoustic emissions, uncomfortable loudness level, masking level difference, SCAN-A, Synthetic Sentence Identification (SSI), and the low predictability section of the Revised Speech in noise (RSPIN). The unmedicated group scored significantly less favorably than the control group on the following tests; SCAN-A (composite, filtered words, and auditory figure ground), R-SPIN (0MCR condition in both the right and left ears). Additionally, the unmedicated group scored significantly less favorably than the medicated group on the SSI (-20MCR condition right ear only) and of the R-SPIN (0MCR condition right ear only). Other test measures indicated consistent trends but did reach significance.

Black Cottonwood (Populus trichocarpa) is a fast-growing, economically important tree species. P. trichocarpa was the first tree to have its genome fully sequenced and is considered the model organism for genomic research in trees. Of the macronutrients in plants, Nitrogen (N) is required in the greatest amounts and is generally the limiting nutrient in terrestrial ecosystems. Inorganic N-transport is performed by four families of transporter proteins, AMT1 and AMT2 for ammonium (NH4+) and NRT1 and NRT2 for nitrate (NO3-). I have created phylogenetic reconstructions of each of these transporter families in 22 members of Viridiplantae whose genomes have been fully sequenced. Based on these phylogenies, I have introduced a new classification system for the transporter families that better represents the evolutionary and functional relatedness of the proteins. These phylogenies were supplemented with topology predictions, subcellular localization predictions, and in silico expression profiling in order to suggest functional characterization of the groups. This facilitated candidate gene selection for NH4+ and NO3- uptake transporters from P. trichocarpa. Expression profiling was performed on two of these candidates. Results suggest that PtAMT1-1 may be a high-affinity, root-localized NH4+ transporter. In contrast, PtNRT2-6 is a high-affinity NO3- transporter localized to the dormant bud, but its physiological functions remain largely enigmatic. Flux profiles of NH4+, NO3-, and H+ in the first 1.4 cm of root tips of three-week-old P. trichocarpa seedlings and cuttings were measured using the Microelectrode Ion Flux mEasurement (MIFE) system to demonstrate the activity of AMTs and NRTs under nutrient-abundant and nutrient-deficient conditions. I found mainly N-efflux from roots of cuttings while seedling roots exhibited N-uptake. This is the first report of such a difference. This highlights an unexpected but clear physiological difference between seedling and cutting roots, which are frequently used in experimental setups. / Graduate / 0817 / 0369 / 0715 / neilvonw@gmail.com

Over the years, biological drugs have evolved and have made breakthroughs in diseases associated with extracellular proteins. However, intracellular proteins that cause disease progression are still largely inaccessible. Examples of diseases that are caused by an intracellular aggregation of proteins are neurodegenerative diseases such as Parkinson's disease, Huntington's disease (HD), and Alzheimer's disease (AD). The purpose of the work is to find a strategy to reach the neurons intracellularly. The goal is to be able to design a biological drug that enters the neuron by investigating different uptake mechanisms. A systematic review of 43 published studies was reviewed, and the results could be obtained. All result presents data from different receptors, cell-penetrating peptides, and adeno-associated viruses (AAV) that were examined. It showed that there are advantages and disadvantages with all the uptake mechanisms. There are risks of side effects for each uptake mechanism, and further studies are required to consider the risk. AAV2 and the neuron-specific receptors lack specific information about their mechanism, but there is a high potential to develop these strategies. Both AVV and the neuron-specific receptors provide specific uptake into tissues.

No description available.

No description available.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Molibdênio é um elemento traço envolvido na fixação de nitrogênio, enxofre e carbono. Oligopeptídeos estão envolvidos na nutrição bacteriana e diversos outros processos de sinalização intercelular. O objetivo do presente estudo foi investigar o papel funcional das proteínas ligadoras dos sistemas de captação de molibdato (ModA) e oligopeptídeo (OppA) em Xanthomonas axonopodis pv. citri em condições in vitro e in vivo. O mutante ModA mostrou uma produção diminuída de goma xantana, alteração do biofilme e adesão prejudicada em condições in vitro. In vivo a interação do mutante modA mostrou alterações nas lesões causadas em folhas de grapefruit possivelmente resultado da baixa expressão do gene gumB. O mutante na proteína OppA apresentou células mais co-agregadas alterando a estrutura do biofilme e consequentemente diminuindo sua capacidade de adesão. In vivo, a linhagem mutante não alterou o fenótipo de patogenicidade, mas a sua capacidade de crescimento foi afetada no início da fase estacionária sugerindo que o sistema Opp desempenha um papel nutricional. / Molybdenum is a trace element involved in nitrogen fixation, sulfur and carbon. Oligopeptides are involved in bacterial nutrition and several other intercellular signaling processes. The aim of this study was to investigate the functional role of binding proteins of molybdate (ModA) and oligopeptide (OppA) uptake systems of Xanthomonas campestris pv. citri in in vitro and in vivo conditions. ModA mutant showed a decreased production of xanthan gum, altered biofilm and adhesion impaired in vitro conditions. In vivo ModA mutant interaction showed changes in injuries on leaves of grapefruit possibly due to low expression of the gumB gene. The OppA mutant showed more cells co-aggregated by changing the structure of the biofilm and consequently reducing their capacity to adhere. In vivo, the mutant strain did not modify the phenotype of pathogenicity, but its ability for growth was affected at the early stationary phase suggesting that the Opp system plays a nutritional role.

O propósito do presente estudo foi investigar as contribuições dos sistemas bioenergéticos e do gasto energético total durante a escalada esportiva indoor. As variáveis antropométricas, a composição corporal, a potência aeróbia máxima de membros superiores e o teste de Wingate para membros superiores foram avaliados em 13 escaladores (Grupo de Elite = 6; Grupo Recreacional = 7). Além disso, o grupo de elite escalou três rotas com diferentes níveis de intensidades (fácil, moderada e difícil) com a mensuração contínua do consumo de oxigênio e com a medida das concentrações sangüíneas de lactato de pico durante a recuperação, ao passo que o grupo dos escaladores recreacionais escalou apenas a rota fácil sobe as mesmas condições. As estimativas dos sistemas aeróbio, glicolítico e ATP-CP foram feitas por meio da mensuração do consumo de oxigênio, das concentrações sanguíneas de lactato de pico e do débito alático de oxigênio, respectivamente. A estimativa do gasto energético total foi realizada pela somatória desses três sistemas. Os principais resultados foram: a) as variáveis antropométricas influenciam apenas em situações específicas da escalada; b) o consumo de oxigênio de pico e a freqüência cardíaca de pico têm uma relação não-linear durante as ascensões das rotas de escalada; c) os sistemas oxidativo e o ATP-CP são os prioritários na transferência da energia na escalada esportiva indoor, independentemente da intensidade das rotas estudadas ou do nível de aptidão dos indivíduos; d) o perfil metabólico e o gasto energético total não apresentam relação linear com o incremento da dificuldade das rotas; e) o menor gasto energético total durante as ascensões está mais relacionado ao desempenho nesse esporte que o aprimoramento dos sistemas bioenergéticos. / The purpose of the present study was to investigate the contributions of the energetic systems and the total energetic cost, during the indoor rock climbing. The anthropometric variables, body composition, upper limbs maximal aerobic power and the Wingate test for the upper limbs were evaluated in 14 climbers (Elite group = 7; Recreation group = 7). Besides, the Elite group have climbed three routes with different levels of intensity (easy, moderate and hard) with the continue measurement of the oxygen uptake during these tasks and with the measurement of the peak blood lactate concentrations during the recovery, while as the recreational climbers group have climbed only the easy route under the same conditions. The calculation of the aerobic, glycolytic and ATP-CP systems were made by the measurement of the oxygen consumption, peak blood lactate concentrations and alactacid oxygen debt, respectively. The calculation of the total energetic cost was made by the sum of these three systems. The main results were: a) the anthropometric variables have secondary contribution on the rock climbers performance, b) the oxygen consumption and the heart rate have a non-linear relation during the ascension of the climbing routes, c) the aerobic and the ATP-CP systems have priority on the energy transference in the indoor rock climbing, independently on the routes intensity or the ability level of the individual, d) the metabolic profile and cost energetic don’t have a linear relationship with the route’s difficult increment; e) the minor energetic cost is more important for the performance in this sport than the improvement of the bioenergetic systems.

Made available in DSpace on 2016-03-22T17:27:15Z (GMT). No. of bitstreams: 1 Francine.pdf: 1635014 bytes, checksum: 766d4215eec29b93b8bf7a4e0d6bed91 (MD5) Previous issue date: 2013-09-27 / The correction of foreign language students errors (corrective feedback) can be considered a useful strategy for teachers in order to help learners in the new language acquisition. Therefore, this work investigates teachers' and learners' (both Portuguese native speakers) beliefs about corrective feedback. It also identifies English language students main errors, the feedback used in the correction and the uptake given, or not, by the students. The study is based on Swain (1995), Ranta (1994), Lyster (2001, 2004), Rauber & Gil (2004), among others. The results indicated that the most used feedback was the recast and that the uptake was not given in all evidences of correction / A correção de erros (feedback corretivo) de alunos de línguas estrangeiras (LEs) pode ser considerada uma estratégia útil para os professores ajudarem os aprendizes na aquisição da nova língua. Partindo desse pressuposto, este trabalho investiga as crenças de alunos e professores falantes de português como L1 sobre o feedback corretivo; identifica os principais erros de alunos de inglês como LE, o tipo de feedback utilizado pelo professor para corrigi-los e o uptake fornecido, ou não, pelo aluno. Para tanto, foram utilizados questionários e transcrições de ocorrência de erros e correções de cinco aulas de três turmas de inglês de nível de proficiência intermediário-avançado. O estudo está fundamentado em autores como Swain (1995), Ranta (1994), Lyster (2001, 2004), Rauber e Gil (2004), entre outros. Os resultados da investigação evidenciaram que o tipo de feedback mais utilizado foi o recast e que nem sempre os alunos forneceram uptake