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Class of 2012 Abstract / Specific Aims: To explore whether publishing requirements for human-centered randomized control trials, particularly the CONSORT criteria, have any relationship to impact as measured by the Journal Citation Reports TM Impact Factor. Methods: A worksheet was used to evaluate a methodically selected list of journals, including types of articles published, requirements of authors for human-focused randomized control trials, JCR Impact Factor and other JCR metrics for each specific journal title. A worksheet was filled out for each journal by each member of the research team and answers combined for consensus. Group means and SDs were calculated and the Student’s t-Test applied to values for selected journals. Main Results: 50 candidate pharmacy journals were identified and 41 met the criteria for publishing human-centered randomized control trials. Journals were grouped according to whether they required CONSORT or had other reporting requirements for human RCTs, or had no requirements for such studies. Few (6; 15%) pharmacy journals required authors to use CONSORT; and additional 15 (37%) journals provided as least some author guidelines similar to CONSORT. Pharmacy journals using CONSORT or other guidelines had a higher average impact factor (3.5; SD = 1.5) than did journals without guidelines (2.4; SD = 0.9; p = 0.007). Conclusions: There appears to be a statistical difference in average JCR metrics between journals which require specific RCT guidelines and those which do not. The use of reporting guidelines, such as CONSORT, by pharmacy journals is associated with increased impact as represented by JCR influence measures.

In this thesis, a feasibility study will be conducted in order to determine if the usage of acontrol moment gyroscope is a possibility for a micro satellite as its attitude control. Thegoal is to conclude if gyroscopes are suitable replacements for the current reaction wheelswhich are acting as the attitude control for the satellite. In the first part of the thesis thegeneral function of the control moment gyroscope and three different types of arrangementsare displayed with all their respective advantages and disadvantages. Then one ofthem will be designed to fit within the restrictions of 1U. The full design of the pyramidconfiguration was chosen due to its compact size and spherical angular momentum envelope.The full design contains all the components such as motors, flywheels, mounts,frame, screws etc. which provide a cost estimate which is a huge input in determiningthe feasibility of this thesis. In the future the manufacture of the pyramid configurablecontrol moment gyroscopes shall be tested in the future with a more advanced steeringlaw in order to determine the full potential of the attitude control system.

Ultrasound irradiation of a protein or polymer solution at the air:water interface can be used to form hollow microspheres containing an air bubble. By introducing a layer of oil and sonicating the oil:water interface, microspheres containing an oil droplet are formed. The microspheres are stabilised by disulfide crosslinking, have diameters of between 1-20 mm and have a number of applications; gas filled protein microspheres are used as ultrasound contrast agents and oil filled microspheres are being developed for delivery of lipophilic drugs. This project extends the scope of sonochemically produced microspheres to include water-in-oil emulsion filled microspheres, which facilitate encapsulation of hydrophilic species, and polymer microspheres that release their contents in response to an external stimulus. Successful encapsulation of a water in oil emulsion phase is demonstrated using confocal microscopy. Release studies are reported for a number of hydrophilic species (in vitro) including 5,6-carboxyfluorescein, 5-fluorouracil and sodium chloride. Release can be triggered by sonochemical disruption of the microsphere shells or cleavage of the disulfide cross links. Thiol-ene coupling reactions initiated by ultrasound irradiation are reported. In water, ultrasound initiation of thiol-ene reactions with electron rich alkenes results in rates of reaction which compare favourably with conventional thermal initiation. Thiol-ene crosslinking is proposed as an alternative to disulfide crosslinking to stabilise sonochemically produced microspheres. Temperature responsive microspheres are produced via the sonochemical method using a block copolymer of N-isopropylacrylamide and thiolated methacrylic acid, P(MASH-b-NIPAm). The block co-polymer is synthesised using reversible addition-fragmentation transfer (RAFT) polymerisation and has a lower critical solution temperature (LCST) of 37 ºC. The microspheres formed from this block copolymer can be seen to rupture, releasing their internal oil phase, when heated above 37 ºC. These findings provide a basis from which to develop sonochemically produced polymer microspheres for responsive delivery of both hydrophilic and lipophilic species.

This work reports the investigation of Cu-mediated polymerization systems and its limits, in order to obtain functional branched polymers, in particular star-shaped and graft-shaped polymers. A novel initiator structure has allowed developing a new approach to synthesise sequence controlled multiblock star polymers via Cu-mediated reversible deactivation radical polymerization (RDRP) in water. This technique allows the preparation of pentablock star shaped polymers in just under 90 minutes of reaction time. The obtained polymers had a good agreement between theoretical and experimental molecular weights and excellent control over molecular weight distribution. Alternatively, the Cu-mediated RDRP of star polymers using a British 1 penny coin was described, displaying similar results as in the literature, providing better experimental conditions. As the copper coin was recovered unharmed, the catalyst was found to be economically very effective. Furthermore, poly(2-ethyl oxazoline) (PEtOx) was polymerized with good control and partially hydrolysed to poly(ethylene imine) (PEI) to yield PEtOx-r-PEI using a microwave reactor. The secondary amines of PEI was converted to macroinitiators, to allow the polymerization of acrylamides in aqueous medium, resulting in graft type polymers based on a poly(oxazoline) backbone with acrylamide side chains. Finally, the synthesis of carbohydrate-monomers was described, which allows to obtain monomers with a different number of carbohydrates (one, two or three). These monomers were polymerised via aqueous SET-LRP, to explore their interaction with carbohydrate binding lectins and to understand the impact on binding of carbohydrate density on polymers and polymer chain length.

CMOS technology scaling has enabled dramatic improvement for digital circuits both in terms of speed and power efficiency. However, most traditional analog-to-digital converter (ADC) architectures are challenged by ever-decreasing supply voltage. The improvement in time resolution enabled by increased digital speeds drives design towards time-domain architectures such as voltage-controlled-oscillator (VCO) based ADCs. The main challenge in VCO-based ADC design is mitigating the nonlinearity of VCO Voltage-to-frequency (V-to-f) characteristics. Achieving signal-to-noise ratio (SNR) performance better than 40dB requires some form of calibration, which can be realized by analog or digital techniques, or some combination. This dissertation proposes a highly digital, reconfigurable VCO-based ADC with lookup-table (LUT) based background calibration based on "split ADC" architecture. Each of the two split channels, ADC "A" and "B", contains two VCOs in a differential configuration. This helps alleviate even-order distortions as well as increase the dynamic range. A digital controller on chip can reconfigure the ADCs' sampling rates and resolutions to adapt to various application scenarios. Different types of input signals can be used to train the ADC’s LUT parameters through the simple, anti-aliasing continuous-time input to achieve target resolution. The chip is fabricated in a 180 nm CMOS process, and the active area of analog and digital circuits is 0.09 and 0.16mm^2, respectively. Power consumption of the core ADC function is 25 mW. Measured results for this prototype design with 12-b resolution show ENOB improves from uncorrected 5-b to 11.5-b with calibration time within 200 ms (780K conversions at 5 MSps sample rate).

PhD / Abstract Low back pain is a significant public health problem in many countries of the world being one of the major causes of work absence and disability. Although the outlook for evidence-based management of low back pain has greatly improved over the past decades, many questions remain. Questions related to treatment options, underlying mechanisms of treatment effects and optimal assessment of low back pain have yet to be fully addressed by researchers. The broad aim of this thesis therefore was to contribute to a better understanding of the contemporary management of low back pain by performing studies in these key research areas. Most clinical practice guidelines recommend exercise as an effective treatment option for chronic low back pain. However the evidence for this recommendation comes from trials that are not placebo-controlled and so this may potentially provide biased estimates of the effects of exercise. Therefore a randomised controlled trial testing the effect of motor control exercise versus placebo in patients with chronic low back pain was conducted. Chapters 2 and 3 describe the trial protocol and the report of the trial respectively. A total of 154 patients with chronic low back pain were randomised to receive a motor control exercise program, or placebo (i.e. detuned short-wave therapy and detuned ultrasound therapy). Primary outcomes were pain, function, and the patient’s global impression of recovery measured at 2 months. The exercise intervention improved function and patient’s global impression of recovery, but not pain, at 2 months. The mean effect of exercise on function was 1.1 points (95%CI, 0.3 to 1.8), the mean effect on global impression of recovery was 1.5 points (95%CI, 0.4 to 2.5) and the mean effect on pain was 0.9 points (95%CI, - 0.01 to 1.8), all measured on 11 point scales. Secondary outcomes also favoured motor control exercise. This is the first study ever to demonstrate that motor control exercise is better than placebo for patients with chronic low back pain. Most of the treatment effects were maintained at 6 and 12 months follow-up. These results suggest that this intervention should be considered for patients with chronic low back pain in order to improve disability, function, and global impression of recovery, and to improve pain intensity in the long term, but not in the short term. Rehabilitative ultrasound imaging (RUSI) has been increasingly used by physiotherapists in order to identify impairments in motor control as well as to monitor progress of patients with low back pain. As with any other clinical measure it is important to know how reproducible the RUSI measures are, and although there are some reproducibility studies in the literature, no systematic review on this topic has been conducted. Therefore a systematic review was performed with the objective of assessing the reproducibility studies of RUSI for abdominal wall muscles (Chapter 4). Eligible studies were indentified via searches in CINAHL, EMBASE and MEDLINE with citation tracking via the Web of Science Index. A total of 21 studies were included. Due to heterogeneity of the studies’ designs, pooling the data for a meta-analysis was not possible. RUSI measures of thickness of abdominal wall muscles were found to be reliable. Few studies analysed the reliability for the measurement of thickness changes (reflecting the muscle activity) finding good to poor results. Evidence for the reproducibility of the difference in thickness changes over time (necessary to evaluate improvements in muscle activity with treatment) was not available. A limitation of the existing literature is that studies typically had suboptimal designs and analysis. The current evidence for the reproducibility of RUSI for measuring abdominal muscle activity is mainly based upon studies with suboptimal designs that included mostly healthy subjects, making generalisability to clinical settings uncertain. Some questions about the reproducibility of RUSI measures of abdominal wall muscles are still unanswered; this is mainly due to design issues, such as inadequate statistics, inadequate sampling and lack of control of sources of bias (e.g. blinding and absence of controlling for ordering effects). In addition the clinically important questions about the reproducibility of thickness changes (reflecting the muscle activity) and differences in thickness changes over time (reflecting the improvement or deterioration of muscle activity) have not been adequately investigated. Therefore a reproducibility study that aimed to answer these questions was performed (Chapter 5). Thirty-five patients seeking care for chronic low back pain participated in this study. RUSI measures were taken at baseline and eight weeks post-baseline. Replicate measures of thickness, thickness changes and differences in thickness changes over time were analysed. The reproducibility of static images (thickness) was excellent (ICC2,1 = 0.97, 95%CI = 0.96-0.97, Standard Error of the Measurement (SEM) = 0.04cm, Smallest Detectable Change (SDC) = 0.11cm), the reproducibility of thickness changes was moderate (ICC2,1 = 0.72, 95%CI 0.65-0.76 SEM = 15%, SDC 41%), while the reproducibility of differences in thickness changes over time was poor. Improvements in the test protocol should be undertaken in order to enhance the reproducibility of RUSI measures, especially for differences in thickness chang over time. Self-report outcome measures (questionnaires) are widely used by health care providers for measuring patient’s health status or treatment outcomes. Most of the questionnaires related to low back pain were developed in English and therefore their usefulness in non-English speaking countries is considerably limited. Cross-cultural adaptation and clinimetric testing are possibly the most efficient methods for solving this problem. Although there are many publications on the topic, a simple guide on how to perform a cross-cultural adaptation and clinimetric testing was not available. Therefore a “clinician-friendly” narrative review for Brazilian physical therapists (Chapter 6) was written. This review aimed firstly to explain the concepts and the relevance of cross-cultural adaptation and clinimetrics testing, secondly to summarise the current guidelines on the topic, thirdly to provide advice on how to choose a relevant questionnaire and finally how to evaluate the quality of an adapted questionnaire. Some examples of cross-cultural adaptations and clinimetrics testing of relevant low back pain questionnaires in the Brazilian-Portuguese language were also provided. Although the number of international versions of low back questionnaires is growing, to date it is unclear which questionnaires have been cross-culturally adapted and into which specific language. To answer these questions a systematic review was conducted in order to describe the available cross-cultural adaptations of low back pain self-report outcome measures and the clinimetric testing that has occurred for each adaptation (Chapter 7). Searches were performed in MEDLINE, EMBASE, CINALH and LILACS; these searches were supplemented with information from experts in the field of low back pain from 27 different countries to ensure that the results were comprehensive. Sixty-one adaptations were identified. While there are a large number of low back pain questionnaires available, very few have been adapted into other languages, particularly commonly spoken languages such as Mandarin, Hindi and Portuguese. The quality and comprehensiveness of clinimetric testing varied considerably, with the evaluation of reliability and construct validity most common. Further cross-cultural adaptation and clinimetric studies are clearly needed and special consideration must be given to study designs for clinimetric testing. The final aim of this thesis was to cross-culturally adapt self-report instruments relevant to the management of low back pain in Brazil. This was achieved by two independent studies. The first study (Chapter 8) aimed to cross-culturally adapt the Functional Rating Index (FRI) into Brazilian-Portuguese and to test the clinimetric properties of the FRI and also of an existing Brazilian-Portuguese version of the Roland Morris Disability Questionnaire (RMDQ) which was not fully evaluated in the original study. Both instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects and internal responsiveness in 140 chronic low back patients presenting for physiotherapy treatment in Brazil. Both instruments were considered reliable and valid for the measurement of disability in Brazilian-Portuguese speakers with low back pain, no ceiling or floor effects were detected, but the internal responsiveness of both instruments was considered small. The second study (Chapter 9) aimed to cross-culturally adapt the Patient-Specific Functional Scale (PSFS) and to perform a head-to-head comparison of the clinimetric properties of the PSFS, RMDQ and FRI. All instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects, internal and external responsiveness in 99 acute low back patients presenting for physiotherapy treatment in Brazil. In order to fully test the construct validity and external responsiveness, it was necessary to cross-culturally adapt the Pain Numerical Rating Scale and the Global Perceived Effect Scale. The results of this study demonstrate that the Brazilian-Portuguese versions of the RMDQ, FRI and PSFS have similar clinimetric properties to each other and to the original English versions; however the PSFS was the most responsive instrument. The results from the studies in Chapters 8 and 9 will benefit the understanding of low back pain by enabling international comparisons between studies conducted in Brazil and English speaking countries. In addition it will encourage researchers to include Brazilian- Portuguese speakers in their future clinical trials. Overall, the studies included in this thesis have provided an important contribution to the contemporary management of low back pain. Firstly the use of motor control exercise could be considered for patients with chronic low back pain as it produces improvements in global impression of recovery, function, disability and pain. Secondly RUSI measures of abdominal wall muscles in patients with low back pain were considered reproducible for the measurement of muscle activity, but not as an outcome measure to detect improvement/deterioration of muscle activity over the course of treatment. Thirdly just a few high-quality cross-cultural adaptations and clinimetrics testing for self-report outcome measures relevant to the management of low back pain are available, and clearly more studies in this area are needed. Finally the Brazilian-Portuguese versions of the Functional Rating Index, the Roland Morris Disability Questionnaire and the Patient-Specific Functional Scale have acceptable clinimetric properties and could be used in clinical practice as well as in research studies in Brazil.

<p>Controlled Source Tensor Magnetotelluric (CSTMT) ground measurements were executed on the Hallandsåsen horst where a major tunnel is under construction. The instrument system EnviroMT are used for this purpose. The major research aspect of this thesis has been to form an opinion of the effectiveness of the method by comparing the results from the CSTMT survey with a prior investigation performed with the DC resistivity method. Another important part of this thesis has been to compile the basic and fundamental CSTMT and RMT theory, in a way that people outside the EM community easily can be introduced to the subject.</p><p>When comparing the different inversion models from the CSTMT and DC resistivity surveys one can see differences in the depth at which the conductors are resolved. In the CSTMT inversion models (TE+TM) there are two conductors that possibly can reach the depth of the tunnel in construction. These conductors are not resolved at the deeper structures in the DC resistivity models. Whether the conductors in the CSTMT inversions (TE+TM) truly extend to the depth at which they are modeled, or if they in deeper parts are artificial effects of regularisation in the inversion cannot be said for sure. Accounting for the low frequencies utilised in the TE mode, one has very strong arguments that the deep conductors seen in the CSTMT model are true.</p><p>The TE-mode models have shown to be much less affected by the complex problems of near field effects in comparison with the TM-mode models. The evidence of the near field effects is very prominent in the TM-mode phase, but in the phase of the TE-mode one can not see any such tendencies. However, one can see a discontinuity in the same part of three profile lines which shows that the data is disturbed but not nearly as much as in the TM-mode. The apparent resistivity seems to be over all less affected by the near field effects. In the apparent resistivity of the TE-mode, one can not discern any near field effects at all.</p><p>In the TM-mode, the apparent resistivity shows higher apparent resistivity than the real apparent resistivity in the near field. To receive more information about the deeper structures, lower controlled source frequencies were allowed in the TE-mode than in the TM-mode inversion models. The RMS in the TE-mode inversions has not been deteriorated, which is an another indication that the TE mode is not very disturbed by the near field effects.</p><p>The RMT inversion models are shown to be heavily biased in the deeper parts to which the RMT data are insensitive and regularization determining the outcome of the inversion. One can also see that regularisation is influencing the whole inversion model. In the shallow subsurface the inversion models should be same for CSTMT and RMT, but one can see differences in resistivity between the models.</p><p>The real induction arrows show features that are not as clearly displayed in either the phase or apparent resistivity. It seems that the real induction arrows are better at detecting lateral differences in conductivity in a more resistive media, than the phase and apparent resistivity.</p>

Graduation date: 1998