Orientador: Lino Lemonica / Resumo: Com o rápido avanço que foi observado nos últimos anos nas técnicas cirúrgicas e anestésicas, os procedimentos se tornaram cada vez mais invasivos. Como houve progressivo envelhecimento da população, o período mais delicado de recuperação, ou seja, o pós-operatório, passou a receber maior atenção. O surgimento de novas técnicas de analgesia, como a Analgesia Controlada pelo Paciente (PCA), vem preencher as necessidades da comunidade médica, cada vez mais atenta à qualidade dos serviços prestados. O Hospital de Clínicas da Faculdade de Medicina da UNESP, Botucatu, atento a essa nova realidade constituiu o Serviço de Dor Aguda (SEDA) para que esta lacuna fosse também preenchida em nosso meio. No intuito de identificar a atuação do SEDA, realizou-se levantamento, de fevereiro de 1995 a dezembro de 1997, com a pesquisa das evoluções de 679 pacientes seguidos pelo SEDA e que fizeram uso do método PCA de analgesia. Observou-se que os resultados obtidos pelo Serviço estavam acima da média relatada pela literatura internacional, com excelentes níveis de analgesia atingidos, baixa ocorrência de efeitos colaterais, e nenhuma complicação fatal no período do estudo. / Abstract: In the past years a fast developing has been observed in the surgery and anesthetic technique, with more invasive procedures being performed. As the general population has becoming older, the critical recovery period, it means the post surgery period, became focus of attention. The developing of new analgesia techniques, such as Patient Controlled Analgesia (PCA), has the intention of fulfill the needs of the medical community, day by day more aware about the quality of the services. The Hospital of the Sao Paulo State Medical School, Botucatu, aware of this new reality had decided to form the Acute Pain Management Service (SEDA). With the goal of identify the way the SEDA acts this research was realized in period between February, 1995, to December, 1997. Data of 679 patients who used the PCA device were evaluated. The results in this study were as good as the international literature shows, with high quality analgesia, low side effects and no fatal complications on the period observed. / Mestre

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Estimation of exposure-specific risks (ESRs) using estimates of the overall risk and relative risk of disease given exposure has been performed in previous studies, but the performance of such an estimator has not been assessed nor has a variance for such an estimate been proposed. In this project I evaluated the performance of a simple product-based ESR and its variance derived using the delta method. I used the variance to estimate the 95% confidence interval. I found that this point estimate was biased and that the accompanying 95% confidence interval did not attain 95% coverage. I also proposed a revised product-based estimator and found that this estimator was unbiased. I used the delta method to derive a variance for this estimator and estimated the 95% confidence interval. The coverage of this interval attained 95% coverage in most situations. According to the CONSORT statement, subgroup analyses in randomized controlled trials (RCTs) should be pre-planned and accompanied with a formal test of interaction. I considered the interaction between treatment and a dichotomous prognostic factor with a continuous outcome. I examined the impact of misspecifying the distribution of the prognostic factor on power and sample size for interaction effects. I found that power for the interaction test was decreased when the misspecification of the distribution of the prognostic factor was away from a balanced design. I also proposed three methods for improving the power under misspecifications. Quota sampling maintained the power at 80%, but trial completion may be delayed under misspecifications. Modified quota sampling improved the power, but results were related to the proportion of trials switching to the quota sampling procedure. Sample size re-estimation improved the power, but did not always attain 80% power. All three methods maintained appropriate type I error. Lastly, I examined the impact of unplanned cross-over on power and sample size for interaction effects in RCTs. Unplanned cross-over is common in surgical trials and can diminish the magnitude of the interaction effect. Due to this, the sample size re-estimation procedure performed better than quota sampling and modified quota sampling in the presence of unplanned cross-over. / 2031-01-02

Evidence-based policing (EBP) has emerged as a key strand of police innovation since Sherman’s (1998) Police Foundation lecture. However, for others EBP raises as many questions as answers. One of the most contentious areas is the role advocated for randomised controlled trials in testing practice and developing knowledge to support EBP. RCTs are controversial with some scholars who argue that policing is not comparable to medicine and that RCTs are unable to reflect the complexity of the police role and context. Even those who advocate the use of RCTs recognise that there are significant challenges in achieving the high dosage and high fidelity that a successful experiment requires. This dissertation responds to these challenges by analysing the completed randomised controlled trials in policing and using a case study, Operation Turning Point, to identify the factors that may contribute to the conduct and management of police field trials with high levels of treatment integrity. In the introduction, Chapter 1, the approach is set out, framed around grounded theory, to be developed in four, linked, chapters. Chapter 2 is focused on understanding treatment integrity in RCTs involving the police: A search for police RCTs is produced 122 Police RCTs completed and reported by 2016. The levels of treatment integrity are analysed. 78 of the 122 RCTs exceeded a 60% threshold, with 49 being above 90%. In Chapter 3, a “novice theory” is developed and tested as an explanation for levels of treatment integrity in police randomised controlled trials: Analysis of the 122 RCTs suggests that “novice theory” can provide an explanation for the general patterns of treatment integrity. Further detailed analysis suggested that there are, however, other factors which may be important in determining the treatment integrity. These are developed in Chapter 4, which centres on a case study of Operation Turning Point. Using published case studies and an analysis of juvenile justice RCTs, a potential framework of operational factors is developed that appear to be important in effective conduct and management. The Turning Point case study is used to develop and expand on those operational factors. Finally, taking the two together, the analysis concluded that, beyond the operational factors, there were some more strategic, “protective factors” that were also critical. These are developed in Chapter 5, by using the coding and analysis of interviews with a sample of key staff involved in Turning Point Our analysis suggests that novice theory needs to be understood in the context of both the operational and protective factors that we have identified. Taken together these findings indicate the potential advantages of building institutional frameworks in which the development of practitioners and researchers and the conduct and management of experimental research could be brought closer together. We conclude with ten recommendations designed to improve the treatment integrity of police RCTs.

The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results.

No description available.

Dysarthria describes the impaired speech intelligibility caused by weakness of muscles involved in speech following stroke. This is a common consequence of stroke and can have a detrimental impact on self-confidence leading to social isolation for many. There is limited evidence for dysarthria intervention but we know that research into speech difficulties after stroke is a priority for stroke survivors. An online speech rehabilitation programme was developed, ReaDySpeech, with the potential to offer improved quality of independent practice, increased intensity of practice and the ability to record interaction. The research presented in this thesis aimed to systematically examine the existing evidence base, to carry out some preliminary acceptability work on ReaDySpeech, and implement a feasibility trial. The initial study was a Cochrane systematic review of the effectiveness of interventions for people with non-progressive dysarthria after stroke or other adult-acquired brain injury. This found insufficient evidence to know whether dysarthria intervention is effective or not. This led to a study of early acceptability work for ReaDySpeech and whether there were any technical barriers to use. This found no significant technical barriers other than lack of Wi-Fi and it was acceptable to participants and therapists. This enabled a progression to a feasibility trial following amendments and improvements to the protocol and ReaDySpeech itself. The feasibility trial found recruitment, retention and the intervention were all feasible to carry out during a trial. Further in-depth consideration of the findings indicates more work is needed to widen recruitment and to develop the intervention, comparator and methodology of a future trial for this to be a success with valid clinical implications. This thesis reports this body of work and discusses potential future directions for dysarthria research.

Class of 2014 Abstract / Specific Aims: To compare trends in user demographics, clinical effects, and clinical outcomes associated with the use of synthetic cannabinoids and cathinones before and after signing into law the Synthetic Drug Abuse Prevention Act of 2012 on July 9, 2012. Methods: Reports generated by the National Poison and Drug Information Center’s Toxic Exposure Surveillance System were used to isolate calls regarding patients who reportedly used either synthetic cannabinoids or synthetic cathinones from July 2011 to March 2013. Clinical effects, clinical outcomes, and demographic information of patients associated with these calls from July 9, 2011 to July 8, 2012, were compared to that of patients associated with calls from July 9, 2012 to July 8, 2013. Main Results: Pending Conclusion: Pending

Background: Due to the “flare effect” associated with the flare protocol, variation in the degree of follicular maturation during stimulation may result in differences in follicle response as compared to the luteal protocol which is based on maximal pituitary suppression and synchronization of follicular maturation. In this study, besides other methods, Anti-Mullerian Hormone (AMH), a novel marker for ovarian reserve, was used as a tool to evaluate the ovarian responsiveness to stimulation. Methods: Women undergoing IVF/ICSI treatment in the UBC IVF Program from January to December 2006 using luteal and flare protocols were retrospectively selected for a total of 40 treatment cycles, 20 cycles in each protocol matched by age, weight, and indication for IVF/ICSI. Serial serum Estradiol (E₂) levels and follicle data were obtained from the clinic chart. Follicle stimulating hormone (FSH), Luteinizing Hormone (LH), progesterone (P), androstenedione (D₄) and AMH levels were measured from aliquots of frozen serum samples. Hormone responses were evaluated by Area Under the Curve (AUC). Data were analyzed using the t-test and statistical significance was considered present at P<0.05. Results are reported as the mean ± SEM. Results: For flare versus luteal protocol, there was a significant difference in the number of total follicles (14.5 ± 1.8 vs 21.3 ± 2.3), medium follicles (3.7 ± 0.6 vs 8.4 ± 1.3), eggs retrieved (8 ± 0.8 vs 14 ± 1.4) and oocytes fertilized (4.4 ± 0.5 vs 8.4 ± 0.7), AMH AUC (62 ± 12 vs 111 ± 13), LH AUC (67 ± 21 vs 20 ± 9), FSH AUC (171 ± 59 vs 112 ± 29), respectively. Mean number of embryos transferred in both groups was similar. Number of pregnancies conceived (5 for flare and 10 for luteal protocol) was not significantly different. Although E₂ AUC in luteal protocol was higher than that in flare protocol, the difference was not statistically significant (28,339 ± 2,669 vs 26,905 ± 2,790). Differences in P and D₄ AUC between the two protocols were not statistically significant. Correlations with ovarian follicles and eggs retrieved were better for AMH than E₂. Conclusions: The luteal protocol exhibited a better ovarian response to stimulation as compared to the flare protocol. As compared to E₂, AMH had a better correlation with the number of follicles and eggs retrieved. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

The present PhD thesis, entitled "Design of novel bio-gated nanomaterials for sensing and therapeutic applications", is focused on the design, preparation, characterization and evaluation of new smart hybrid organic-inorganic materials for their applications on the field of sensing and controlled drug delivery. The first chapter of this thesis introduces the concept of organic-inorganic hybrid materials containing switchable "gate-like" ensembles and their applications in the detection of chemical and biochemical species and as suitable materials for drug delivery applications. The second chapter describes the preparation of an aptamer-capped mesoporous material for the fluorogenic detection of thrombin in human plasma and serum. For the preparation of the material dye-loaded MCM-41 particles were capped with a thrombin aptamer (TBA). In the presence of thrombin, TBA was displaced from the surface due to the formation of TBA-protein complex, triggering the release of the dye. The capped system was tested in simulated human blood plasma and in PBS buffer with 10% of human serum and achieved a low limit of detection (LOD) for thrombin. Moreover, the prepared material displayed great selectivity for thrombin in the presence of other non-exclusive binding proteins. The gated-nanomaterial resulted suitable to perform an accurate thrombin detection in human serum. In the third chapter a new fluorogenic sensing nanoprobe for the detection of As(III) is described. The system consists of the combination of MSNs with an aptamer (Ars-3), which possesses a very high affinity to As(III), as a pore blocking agent. The sensitivity of the nanocarrier for As(III) was further studied. Furthermore, the selectivity of the nanocarrier towards As(III) in the presence of other cations was also successfully verified. In addition, the sensor allowed accurate As(III) determination in real media. The fourth chapter reports a novel proof-of-concept to detect Mycoplasma genomic DNA and cocaine. The new approach combined gated mesoporous silica nanoparticles and surface-enhanced Raman scattering (SERS) spectroscopy. In particular, two gated-hybrid mesoporous materials loaded with a SERS reporter and capped with suitable oligonucleotide sequences to detect Mycoplasma genomic DNA or cocaine, were prepared. Release of the reporter was triggered from the different materials by the presence of the corresponding target, and was detected by SERS upon adsorption on gold nanotriangles. This novel procedure allowed detecting Mycoplasma genomic DNA and cocaine with a high selectivity and sensitivity. The fifth chapter describes the development of a nanodevice able to deliver insulin as a function of the glucose concentration, in simulated human blood plasma. The glucose-driven nanomaterial consisted of ß-cyclodextrin-modified glucose oxidase (CD-GOx)-capped silica nanoparticles loaded with insulin. The reaction of glucose by the capping enzyme (GOx) triggered insulin release in a self-regulated manner. Furthermore, the response to glucose was found to be selective and other saccharides were unable to deliver the entrapped insulin. We hope the results obtained in this thesis may inspire further works to design smart nanodevices with application in analytical chemistry, clinical or environmental assays and self-regulated drug delivery systems. / La presente tesis doctoral, titulada "Diseño de nuevos nanomateriales con puertas moleculares biológicas para aplicaciones de detección y terapéuticas", se centra en el diseño, preparación, caracterización y evaluación de nuevos materiales híbridos orgánicos-inorgánicos inteligentes para su aplicación en el campo de la detección y liberación controlada de fármacos. El primer capítulo de la presente tesis introduce el concepto de los materiales híbridos orgánicos-inorgánicos funcionalizados con puertas moleculares y su aplicación en la detección de especies químicas y bioquímicas de interés y como materiales adecuados para su aplicación en liberación controlada de fármacos. El segundo capítulo describe la preparación de un material mesoporoso con aptámeros como puerta moleculares, para la detección fluorogénica de trombina en plasma y suero humano. En la preparación del material se utilizaron partículas de MCM-41 cargadas con un colorante y cuyos poros se taparon con un aptámero que reconoce la proteína trombina (TBA). En presencia de trombina el TBA se desplazó de la superficie debido a la formación del complejo TBA-proteína permitiendo así la liberación del colorante. El funcionamiento del material se evaluó en plasma humano simulado y en PBS con 10% de suero humano y se alcanzó un bajo límite de detección (LOD) para trombina. Además, el material resultó ser selectivo para trombina en presencia de otras proteínas no específicas. El nanomaterial resultó adecuado para la detección precisa de trombina en suero humano. En el tercer capítulo se describe una nuevo nanomaterial sensor para la detección fluorogénica de As (III). El sistema consiste en la combinación de nanopartículas mesoporosas de sílice (MSNs) con un aptámero (Ars-3), que posee una alta afinidad por el As(III), como agente bloqueante de los poros. Además, se estudió la sensibilidad del nanomaterial para As(III). Por otro lado, se demostró la selectividad del nanomaterial para As(III) en presencia de otros cationes. Adicionalmente, el sensor permitió una determinación precisa de As(III) en un medio real. El cuarto capítulo describe una novedosa prueba de concepto para la detección de ADN genómico de Mycoplasma y cocaína. El nuevo enfoque combinó MSNs con puertas moleculares y espectroscopía Raman amplificada en superficie (SERS). En particular, se prepararon dos materiales híbridos con puertas moleculares y cargados con un reportero SERS. Como puertas moleculares se utilizaron dos secuencias de oligonucleótidos para detectar ADN genómico de Mycoplasma o cocaína. La liberación del reportero SERS desde los materiales se indujo por la presencia del analito correspondiente, y fue detectado por SERS tras su adsorción sobre nanotríangulos de oro. Este nuevo procedimiento permitió detectar ADN genómico de Mycoplasma y cocaína con alta selectividad y sensibilidad. El quinto capítulo describe el desarrollo de un nanodispositivo capaz de liberar insulina en función de la concentración de glucosa en plasma sanguíneo humano simulado. El nanomaterial consiste en nanopartículas de sílice funcionalizadas cuyos poros se taparon con la enzima glucosa-oxidasa modificada con ß-ciclodextrinas (CD-GOx) y cargadas con insulina. La reacción de la glucosa por la enzima bloquenate (GOx) desencadenó la liberación autorregulada de insulina. Asimismo, se encontró que la respuesta a la glucosa era selectiva y otros azúcares no indujeron la liberación de la insulina cargada. Esperamos que los resultados obtenidos en esta tesis puedan inspirar otros trabajos para diseñar nanodispositivos inteligentes con aplicación en la química analítica, ensayos clínicos o medioambientales y en sistemas de liberación autorregulada de fármacos. / La present tesi doctoral, titulada "Disseny de nous nanomaterials amb portes moleculars biològiques per a aplicacions de detecció i terapèutiques", es centra en el disseny, preparació, caracterització i avaluació de nous materials híbrids orgànics-inorgànics intel·ligents per a la seua aplicació en el camp de la detecció i lliberació controlada de fàrmacs. El primer capítol de la present tesi introduïx el concepte dels materials híbrids orgànics-inorgànics funcionalizats amb portes moleculars i la seua aplicació en la detecció d'espècies químiques i bioquímiques d'interés i com a materials adequats per a la lliberació controlada de fàrmacs. El segon capítol descriu la preparació d'un material mesoporós amb aptámeros com a porta molecular, per a la detecció fluorogénica de trombina en plasma i sèrum humà. En la preparació del material es van utilitzar partícules de MCM-41 carregades amb un colorant i els porus del qual es van tapar amb un aptàmer que reconeix la proteïna trombina (TBA). En presència de trombina el TBA es va desplaçar de la superfície a causa de la formació del complex TBA-proteïna permetent així l'alliberament del colorant. El funcionament del material es va avaluar en plasma humà simulat i en PBS amb 10% de sèrum humà i es va aconseguir un baix límit de detecció (LOD) per a trombina. A més, el material va resultar ser selectiu para trombina en presència d'altres proteïnes no específiques. El nanomaterial va resultar adequat per a la detecció precisa de trombina en sèrum humà. En el tercer capítol es descriu un nou nanomaterial sensor per a la detecció fluorogènica d'As(III). El sistema consistix en la combinació de nanopartícules mesoporoses de sílice (MSNs) amb un aptàmer (Ars-3), que posseïx una alta afinitat per l'As(III), com a agent bloquejant dels porus. A més, es va estudiar la sensibilitat del nanomaterial per a As(III). D'altra banda, es va demostrar la selectivitat del nanomaterial per a As(III) en presència d'altres cations. Addicionalment, el sensor va permetre una determinació precisa d'As(III) en un medi real. El Quart capítol descriu una nova prova de concepte per a la detecció de ADN genòmic de Mycoplasma i cocaïna. El nou enfocament va combinar MSNs amb portes moleculars i espectroscòpia Raman amplificada en superfície (SERS). Concretament, es van preparar dos materials híbrids amb portes moleculars i carregats amb un reporter SERS. Com a portes moleculars es van utilitzar dos seqüències d'oligonucleòtids per a detectar ADN genòmic de Mycoplasma o cocaïna. L'alliberament del reporter SERS des dels materials es va induir per la presència de l'anàlit corresponent, i va ser detectada per SERS després de la seua adsorció sobre nanotriangles d'or. Este nou procediment va permetre detectar ADN genòmic de Mycoplasma i cocaïna amb alta selectivitat i sensibilitat. El quint capítol descriu el desenrotllament d'un nanodispositiu capaç d'alliberar insulina en funció de la concentració de glucosa en plasma sanguini humà simulat. El nanomaterial consistix en nanopartícules de sílice funcionalizades els porus del qual es van tapar amb l'enzim glucosa-oxidasa modificada amb ß-ciclodextrinas (CD-GOx) i carregades amb insulina. La reacció de la glucosa per l'enzim bloquejant (GOx) va desencadenar l'alliberament autoregulat d'insulina. Així mateix, es va trobar que la resposta a la glucosa va ser selectiva i altres sucres no van induir la lliberació de la insulina carregada. Esperem que els resultats obtinguts en aquesta tesi puguen inspirar nus treballs per a dissenyar nanodispositius intel·ligents amb aplicació en la química analítica, assajos clínics o mediambientals i en sistemes de lliberació autoregulada de fàrmacs. / Oroval Cucarella, MDM. (2017). Design of novel bio-gated nanomaterials for sensing and therapeutic applications [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/78836 / TESIS

The United States has established breastfeeding as an important health indicator within the Healthy People agenda. Healthy People target goals for breastfeeding initiation, duration, and exclusivity remain unmet. The US Surgeon General's Office reports that lack of knowledge and widespread misinformation about breastfeeding are barriers to meeting Healthy People goals. Breastfeeding mothers are vulnerable to messages that cast doubt on their ability to breastfeed. Very little research has examined specific approaches to help people resist negative messages about health beliefs and behaviors. The objective of this quasi-experimental study was to test an intervention designed to help mothers defend their breastfeeding decisions and resist influences that attempted to persuade them to give formula to their babies. Women attending prenatal breastfeeding classes were recruited and assigned to comparison and intervention groups. The intervention was a board game based on McGuire's inoculation theory of resistance to influence. Controlling for intention to breastfed, intervention and comparison groups were examined for differences in maternal self-efficacy to resist persuasion to give formula and breastfeeding rates for initiation, duration, and exclusivity. Data analyses consisted of analysis of covariance and logistic regression. There was no significant difference between comparison and intervention groups, both groups had high self-efficacy to resist giving formula to their babies; nor were there significant differences regarding breastfeeding initiation, duration and exclusivity. The lack of significant differences may have been influenced by ceiling effects in all of the breastfeeding variables, possibly due to the high socioeconomic level of the sample. The intervention may have worked better in women who were more prone to dissuasive influence, such as those with lower education.