The thermostability of vaccines is of crucial importance in Africa, where the logistical process to get the vaccine from the manufacturer to the animal may take months, and in many remote regions transport and storage is in the absence of a cold-chain. Vaccines with improved stability and less reliance on a cold-chain are needed and could improve the longevity of immune responses elicited in vaccinated animals. In South Africa, cattle in the vaccination zone neighbouring the Kruger National Park have to be vaccinated thrice annually because of declining antibody responses at three months postvaccination. FMDV is known to be unstable, especially for O and SAT2 serotypes in mildly acidic pH conditions or at elevated temperatures, leading to dissociation of the capsid (146S particle) and loss of immunogenicity. The link between rapidly declining antibody responses and capsid stability have been reported by Doel and Baccarini, 1981. We hypothesized that more stable viruses, especially thermostability, will not only improve the protective immune response in animals but also require less frequent booster vaccinations. / The residues at the capsid inter-pentamer interfaces, and their interactions, are important for the infectivity and stability of the virion and mutations adjacent to these interfaces have an effect on the conformational stability of FMDV. However, experimental studies on the relative importance of residues and molecular interactions in viral capsid assembly, disassembly, and/or stability are still very limited, especially for the SAT serotypes of FMDV. This study investigated the effects of potential residues at the pentameric interfaces that are responsible for increased thermostability and potentially improved stability candidates were tested in small (guinea pigs) and large (cattle) animal vaccination trials to understand the role of stabilised antigens on immune responses. The biological variation in biophysical stability in SAT2 viruses in the southern Africa region was investigated to determine if any naturally occurring viruses have greater capsid thermostability. Naturally occurring stable viruses could be used as prospective candidates in vaccine production and therefore potentially result in increased duration of immune responses. / Our first aim was to investigate the role of different amino acid changes at the interface and their effect on capsid stability using models derived by Oxford University. These changes were introduced by mutating the SAT2 ZIM7/83 infectious genome-length clone (pSAT2) to derive mutated chimeric SAT2 viruses. We quantified the stabilizing effects of these mutations by using various stability assays. We established the novel thermofluor shift assay that is able to quantify the capsid stability of viruses. The growth kinetics, antigenicity, genetic stability, pH and salt sensitivity were investigated for each of the genetically engineered viruses (Chapters 2 and 3). / The second aim was to further our understanding on the correlation between improved stability and immune responses by performing small animal (Chapter 2) and large animals trials in cattle (Chapter 4) and comparing stabilised and wild-type antigens. This study for the first time for SAT vaccines, determined differences in IgG1 and IgG2 profiles, interferon gamma (IFN-γ) responses and differences in total and neutralising antibodies of stabilised and wild-type antigens over a six month period in cattle (Chapter 4). Animals were intra-dermolingually challenged with live virus to determine levels of protection the antigens have afforded. / In addition, a third aim will be to better understand the inherent thermostability variation of SAT2 viruses in the Southern African region (Chapter 5) by establishing a protocol for screening field isolates as potential vaccine strains and correlating their stability to amino acid residues at the interface of the 146S particles. / Thesis (PhD)--University of Pretoria, 2016. / Agricultural Research Council / Veterinary Tropical Diseases / PhD / Unrestricted

Ankle foot orthosis (AFO) stiffness affects ankle range of motion but can also provide energy storage and return to improve mobility. To perform multiple activities during the day, a person may want to change their AFO stiffness to meet their activity’s demand. Carrying multiple AFO and changing the AFO is inconvenient and could discourage users from engaging in multiple activities. This thesis developed a new quick-release mechanism (QRM) that allows users to easily change posterior strut elements to change AFO stiffness. The QRM attaches to the AFO and requires no tools to operate. The new QRM includes a quick-release key, weight-bearing pin, receptacle anchor, and immobilization pin. A prototype was modelled with SolidWorks and simulated with SolidWorks Simulation. The QRM was designed to have no mechanical failure during intense activities such as downhill walking and running. Unlike a solid screw connection, the QRM needed an additional part to eliminate unsecured motion related to clearance between the quick release key and receptacle anchor. Mechanical test results and measurement data demonstrated no deformation on each part after mechanical testing. User testing revealed that, although the quick release mechanism can be locked or unlocked rapidly, the person’s posture when operating can facilitate strut swapping. A learning effect occurred by repeated practice. The Quick Release AFO (QRAFO) prototype verified the manufacturing feasibility of the QRAFO design. Overall, the novel quick release AFO improved strut swapping time without sacrificing device strength.

Within East African countries many of the known infectious diseases of animals occur commonly and are poorly controlled. Foot-and-mouth disease (FMD) is one of the contagious viral diseases that has great impact on economic development both in terms of direct and indirect losses. The epidemiology of the disease is complex due to the presence of six of the seven serotypes and the presence of large numbers of both wild and domestic susceptible animals in the region. Decision-making to determine the importance of FMD control relative to the economic consequences and what FMD control strategies should be applied based on the epidemiological information is required. In this regard the first step is to investigate the genetic relationships/variability of East African isolates and their phylogeographic distribution. These can provide base-line information for designing control strategies by vaccination as well as the determination of the sources of infection. Sufficient genetic information on the FMO serotypes O, SAT-1 and SAT-2 are lacking and therefore the number of viral Iineages and genotypes or topotypes from East African countries could not be determined. Published studies on the relative occurrence and genotype distribution of FMO are largely confined to the southern and western part of the continent. In this study, the genetic profile of the 3 most prevalent serotypes (0, SAT-2 and SAT-1) recovered from outbreaks in East Africa between 1957 and 2003 was addressed. Phylogenetic analysis of partial and complete sequences of the 10 gene revealed the presence of distinct lineages and genotypes for East Africa as well as historical relationships of some of the genotypes with isolates from other regions. A great variation in the occurrence and distribution of these serotypes were found. All the African and the Middle East/South East Asian isolates of serotype O included in this study clustered into one lineage having 8 distinct topotypes. These results indicated that between countries as well as inter-regional (east and west Africa) spread of viruses occurred in the past. Inter-regional spread of the virus between eastern Africa and western Africa was also confirmed for SAT-1 viruses. The fact that phylogenetic links are found with both serotypes implies that the spread of viruses was possibly associated with unrestricted animal movement due to nomadic movement in Africa. The phylogenetic relationships of SAT-1 viruses are more diversified in Africa. Eight lineages and 11 genotypes were identified when the optimal nucleotide sequence differences of ≥ 23% for lineages and ≥ 6% for genotypes were used as a cut-off values. It was observed that viruses from Uganda are evolving independently from viruses elsewhere on the continent and clustered into 3 discrete lineages. In contrast, viruses from countries neighbouring Uganda, Kenya and Tanzania, clustered into one lineage. Uganda also harboured 3 topotypes of SAT-2 virus isolates, one is distinct for Uganda and the other are shared with Kenya and Zaire (DRC). This study highlighted distinct lineages found in Uganda and needs further investigation. Within SAT-2, 67 isolates from 22 African countries and Saudi Arabia clustered into 5 lineages which consisted of 15 genotypes. Clustering of viruses into distinct genotypes (topotypes) according to year of isolation and geographical origin was observed showing countries with common boundaries shared common epizootics in the past. These results also showed a link between eastern and southern African countries. Attempts were also made to investigate the incidence of FMD in Ethiopia using sera collected from cattle, small ruminants and wildlife. The results obtained from the liquid phase blocking ELISA and the 3ABC ELISA indicated the presence of SAT-1 and SAT-2 in buffalo populations in the southern part of Ethiopia while results from small ruminants and other wildlife were not indicative of any significant role in the epidemiology of FMD. Serological results also indicated that SAT-1 is present in cattle, although this serotype has not been previously identified. The cumulative molecular epidemiological results from this and previous studies indicated that genetic variability of FMD viruses can be independently maintained within country/countries or regions as well as inter-regions of Africa. The serological results from buffaloes in East Africa are also suggestive of a possible reservoir of the SAT types FMD in the region which has a great impact on the control of the disease. Furthermore, the numerous lineages and genotypes of FMD virus isolates in Africa having distinct or overlapping distributions as well as the genetic linkage between regions will complicate the epidemiology of the disease. Therefore, it is strategically important to consider a regional approach and the use of a vaccine which contains a cocktails of antigens of FMD virus strains. / Thesis (PhD)--University of Pretoria, 2004. / Veterinary Tropical Diseases / unrestricted

No description available.

No description available.

This thesis presents an engineering approach to the modeling and analysis of custom foot orthotics. Although orthotics are widely used and accepted as devices for the prevention of and recovery from injuries, the design process continues to be based on empirical means. There have been many clinical studies investigating the various effects that the orthotics can have on the kinematics and kinetics of human locomotion. The results from these studies are not always consistent, primarily due to subject variability and experimental nature of the design. Alternatively, a better understanding of the therapeutic effects of custom foot orthotics, as well as designing for optimal performance, can be achieved through simulation-based engineering modeling and analysis studies. Such an approach will pave the way to clarify some of the ambiguous findings found in the clinical studies-based literature. Towards this goal, this research presents a methodical process for the replication of the orthotics’ complex three-dimensional geometry and for the construction of finite element analysis models using estimated nonlinear material properties. As part of this research, laser scanning techniques are used to capture the objects’ details and geometry through generation of point cloud surface images by taking multiple scans from all angles. Material testing and Mooney-Rivlin equations were used to construct the hyperelastic nonlinear material properties. Using the mid-stance phase of gait for loading conditions, the ANSYS finite element package was utilized to run analyses on three different load classifications and the corresponding maximum stresses and deflection results were generated. The results indicate that the simulated models can augment and validate the use of empirical tables for designing custom foot orthotics. They can also provide the basis for the optimal design thicknesses of custom foot orthotics based on an end-users’ weight and activities. From a practical perspective, they can also be useful in further exploring different orthotics, loading conditions, material properties, as well as the effectiveness of orthotics for different foot and lower extremity deformities.

The Port of Oakland (“Port”) is the 5th largest container seaport by volume in the U.S. and the largest in Northern California. Maritime shipping activity at the Port exceeds 2 million import and export twenty-foot equivalent unit (TEU) containers annually. Containers may be full or empty, but nonetheless typically require hinterland shipment and intermodal transfer between maritime and land-based freight distribution systems. The freight trucking mode (“drayage”) handles approximately 80% of all TEU throughput at the Port, thus constituting the majority of landside Port traffic. The Port is also situated adjacent to dense urban development thereby exacting certain external impacts. Drayage impacts on regional roadway infrastructure proximate to the Port are explored, to expand knowledge of freight network conditions and relevant policies addressing the topic in the San Francisco Bay Area. Statistical regression analysis and elasticity results estimate a certain level of impact on nearby freight corridors of I-80, I-680, and I-880. Drayage traffic has continued to increase since 2000, as a function of increasing TEU throughput occurring at the Port. Policies to address stable freight flow and infrastructure maintenance are ongoing, although additional studies are also recommended to ascertain comprehensive network impacts.

Ankle foot orthoses (AFOs) are used to improve walking in some lower extremity conditions but AFOs restrict ankle motion resulting in a trade-off in ankle and hip mechanics. While the use of AFOs have been well documented, there still remain gaps in the literature. The first study compared the differences in sagittal plane ankle and hip kinematics and kinetics across three conditions at two speeds in healthy individuals while the second study compared frontal plane kinetics at the hip and knee and vertical ground reaction forces between two conditions at two speeds in healthy individuals. This was studied by collecting and analyzing three-dimensional joint kinematics and ground reaction forces from twelve healthy adults. Participants walked in three conditions (shod; i.e. athletic shoes only and two reduced push-off conditions using solid ankle foot orthoses (SAFOs); i.e. unilateral brace and bilateral brace conditions) and at two speeds (1.25m/s and 1.5m/s). In the first study, generalized linear models with general estimating equations were used to compare ankle and hip angles, moments and power for the braced and unbraced sides separately in all three conditions. In the second study, frontal plane kinetics and vertical ground reaction forces in the unbraced limb in the unilateral brace condition were compared to the same side during shod walking using paired sample t-tests. From our first study we found that the reduced push-off from the use of SAFOs results in decreased peak plantarflexion angles and power generation at the ankle and increased peak flexion angles, and first and second peak power generation at the hip in the braced limbs in both unilateral (p≤0.05) and bilateral (p≤0.05) brace conditions at both speeds. On the unbraced side in the unilateral brace condition, there were decreased peak power generation at the ankle at 1.25m/s and increased peak extension moments, first and second peak power generation at the hip compared to the shod condition (p<0.05) at both speeds. In the comparison between the unilateral and bilateral brace conditions, the changes in ankle and hip mechanics were similar to the changes between the shod condition and the bilateral brace condition on the unbraced side; in addition, participants also had higher peak extension moments in the unilateral brace condition compared to the bilateral brace condition (p<0.05). On the braced side, participants had lower peak plantarflexion moments at the ankle and lower peak flexion angles at the hip when walking with bilateral SAFOs, compared to walking with unilateral SAFOs (p<0.05). In the second study, we found that peak internal knee and hip abduction moments were 3% and 4% higher, respectively, in the unbraced limb in the unilateral brace condition at 1.25m/s (p≤0.041) compared to the same side in the shod condition. Peak vertical ground reaction force was 3% higher in the unbraced limb in the unilateral brace condition at both speeds (p=0.002). Findings indicate that walking with unilateral ankle foot orthoses presents an increased risk of developing secondary conditions.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Background: There is lack of measurement methods to evaluate postoperative rehabilitation for people who have undergone orthopedic surgery of the foot at Uppsala University Hospital. One objective method is to measure muscle strength with MicroFET2, which is available at the hospital. Before implementing the method it is necessary to ensure the the reliability of supination and pronation measured with MicroFET2 because there are no studies that have explored this. Pronators and supinators are important muscles for the stability of the foot and to the arch of the foot. Objective: To examine intra-rater reliability of peak strength of pronation and supination of left and right foot using handheld dynamometer (MicroFET2) in adults without leg- or footpain. Methods: The intra-rater reliability was evaluated in 24 adults by test-retest with 7 days between measures. The test were supination and pronation of the left and right foot. Interclass correlation coefficient (ICC 2,1) and standard error of measurement (SEM and SEM%) were calculated. Results: The results from this study showed high intra-rater reliability for both supination and pronation with ICC between 0.73-0.88 for mean of three trials and 0.74-0.89 for highest value of three trials. SEM och SEM% varied between 14.5-24.4 N and 7.7-11.9% at mean of three trials and 14.1-25.6 N and 7.2-11.9% at highest value of three trials. Conclusion: MicroFET2 is a reliable instrument to measure strength in the foot supinator and pronator-muscles in healthy adults. / Bakgrund: Vid Akademiska sjukhuset i Uppsala saknas det ett objektivt sätt att mäta maximal muskelstyrka vid rehabilitering efter fotoperation. En objektiv mätmetod för maximal muskelstyrka är dynamometern MicroFET2 som finns på sjukhuset. För att implementera denna metod behövs säkerställande av reliabiliteten för pro- och supination mätt med MicroFET2 eftersom det saknas studier som undersöker detta. Pronatorer och supinatorer är viktiga muskelgrupper för fotens stabilitet och fotvalv. Syfte: Undersöka intrabedömarreliabilitet vid maximal isometrisk muskelstyrka av höger och vänster fots supinatorer och pronatorer med handhållen dynamometer (MicroFET2) hos vuxna individer utan ben- eller fotsmärta. Metod: Intrabedömarreliabiliteten undersöktes genom test-retestförfarande med 7 dagars intervall på 24 personer. Muskelgrupper som mättes var fotens supinatorer och pronatorer på både höger och vänster fot. Interclass correlation coefficient (ICC 2,1) samt standard error of measurement (SEM och SEM%) beräknades. Resultat: Resultatet från studien visar på hög relativ intrabedömarreliabilitet i både supination och pronation med ICC mellan 0.73-0.88 vid medelvärde av tre försök och mellan 0.74-0.89 vid högsta värde av tre försök. SEM och SEM% varierade mellan 14.5-24.4 N och 7.7-11.9% vid medelvärde av tre försök respektive mellan 14.1-25.6 N och 7.2-11.9% vid högsta värde av tre försök. Slutsats: MicroFET2 är ett reliabelt instrument för att mäta styrka i fotens pronatorer och supinatorer på friska vuxna personer.