Background: Many nursing home residents are at risk of developing a pressure ulcer, which is an area of localised damage to the skin and/or underlying tissue due to immobility, increasing age and co-morbidities. Whilst guidelines for the prevention of pressure ulcers exist, their implementation can be sub-optimal. Care bundles are a set of research-informed practices used to facilitate the implementation of evidence into practice and incorporating psychological theory within their development may enhance their effectiveness. I aimed to co-design and assess the feasibility of implementing a theory and research-informed pressure ulcer prevention care bundle intervention in a nursing home setting. Method: This thesis comprised four separate studies as part of an overall mixed methods research design. Firstly, I conducted a systematic review and meta-analysis to determine the effects of care bundles per se on patient outcomes. I then conducted theory-informed qualitative, semi-structured interviews with nursing home care staff and NHS community-based nurses to explore the context of, and the barriers and facilitators to, pressure ulcer prevention in nursing homes. Next I co-designed a pressure ulcer prevention care bundle with 13 healthcare workers during a four hour workshop and supplemental email consultation. Using the Nominal Group Technique, we reached a consensus about the content of the care bundle. Following the steps of the Behaviour Change Wheel, I finalised the care bundle intervention. The final study involved a before-after study design where one nursing home implemented the care bundle intervention. I collected and analysed quantitative and qualitative data to gain a more holistic understanding of the feasibility issues related to the implementation. Findings: Findings from the systematic review suggested that care bundles may reduce the risk of negative outcomes in patients. These findings were based on very low quality evidence and the original study authors rarely reported adherence to the care bundle interventions. The theoretical understanding of the complexities in the prevention of pressure ulcers in nursing homes suggested there were four barriers and six facilitators, which my final care bundle intervention addressed. The co-designed care bundle intervention comprised three elements: support surfaces, skin inspection, repositioning; alongside three intervention functions and seven behaviour change techniques. In the final feasibility study, during the baseline period, there were 462 resident bed days and 5 new pressure ulcers recorded and in the intervention phase there were 1,181 resident bed days and no new pressure ulcers. The care bundle intervention appeared to be acceptable to the nursing home care staff and we have identified specific issues relating to the feasibility of implementing the care bundle intervention. Conclusions: The current research evidence-base for care bundles is poor. However, it was possible to co-design and implement a pressure ulcer prevention care bundle intervention for a nursing home setting. Further feasibility research is necessary before we can assess whether the care bundle intervention is effective in preventing pressure ulcers in nursing homes.

acase@tulane.edu

<p>This thesis describes the design and synthesis of molecules with potential roles in biomedicine, with an emphasis on molecular recognition in complex biological environments. The first chapter describes the synthesis and evaluation of compounds for use in nuclide therapy. Carboranes are frequently used in the development of drugs for Boron Neutron Capture Therapy. New routes for monohydroxylation at the B and C atoms of <i>p</i>-carborane have been developed. The Suzuki-Miyaura reaction has been applied to the cross-coupling of <i>bis</i>(neopentyl glycolato)diboron or <i>bis</i>(pinacolato)diboron and 2-I-<i>p</i>-carborane. The synthesized derivatives are important intermediates in the synthesis of a number of potentially biologically active carborane-containing molecules.</p><p>The DNA intercalator doxorubicin has been functionalized to enable ¹²⁵I labelling. The aim of combining the DNA intercalator with ¹²⁵I was to achieve high delivery of cytotoxic radiation to the nucleus. The DNA-binding ability and cellular uptake of the synthesized compounds have been evaluated. One of the compounds bound strongly to DNA and had similar cellular uptake as daunorubicin, which makes the compound very interesting for further biological evaluation.</p><p>The second chapter describes the use of polypeptide conjugates to broaden our knowledge of molecular recognition. The polypeptides consist of 42 amino acids each and are designed to fold into helix-loop-helix motifs that dimerize due to their amphiphilic character. The polypeptides are combined with a variety of small organic molecules. The incorporation of small aromatic molecules to influence the structure and dynamics of a polypeptide has been investigated. By attaching a dansyl group to the side chain of a lysine residue, the dynamics of the protein’s hydrophobic core where affected to such a degree that a native-like fold was formed. The polypeptide conjugates have also been used to study the binding and recognition of native proteins. High-affinity binders for chitinases and acetylcholine esterase have been developed and evaluated.</p>

This thesis describes the design and synthesis of molecules with potential roles in biomedicine, with an emphasis on molecular recognition in complex biological environments. The first chapter describes the synthesis and evaluation of compounds for use in nuclide therapy. Carboranes are frequently used in the development of drugs for Boron Neutron Capture Therapy. New routes for monohydroxylation at the B and C atoms of p-carborane have been developed. The Suzuki-Miyaura reaction has been applied to the cross-coupling of bis(neopentyl glycolato)diboron or bis(pinacolato)diboron and 2-I-p-carborane. The synthesized derivatives are important intermediates in the synthesis of a number of potentially biologically active carborane-containing molecules. The DNA intercalator doxorubicin has been functionalized to enable 125I labelling. The aim of combining the DNA intercalator with 125I was to achieve high delivery of cytotoxic radiation to the nucleus. The DNA-binding ability and cellular uptake of the synthesized compounds have been evaluated. One of the compounds bound strongly to DNA and had similar cellular uptake as daunorubicin, which makes the compound very interesting for further biological evaluation. The second chapter describes the use of polypeptide conjugates to broaden our knowledge of molecular recognition. The polypeptides consist of 42 amino acids each and are designed to fold into helix-loop-helix motifs that dimerize due to their amphiphilic character. The polypeptides are combined with a variety of small organic molecules. The incorporation of small aromatic molecules to influence the structure and dynamics of a polypeptide has been investigated. By attaching a dansyl group to the side chain of a lysine residue, the dynamics of the protein’s hydrophobic core where affected to such a degree that a native-like fold was formed. The polypeptide conjugates have also been used to study the binding and recognition of native proteins. High-affinity binders for chitinases and acetylcholine esterase have been developed and evaluated.

Experimental data on SuperCritical-Water (SCW) cooled bundles are very limited. Major problems with performing such experiments are: 1) small number of operating SCW experimental setups and 2) difficulties in testing and experimental costs at very high pressures, temperatures and heat fluxes. However, SuperCritical Water-cooled nuclear Reactor (SCWRs) designs cannot be finalized without such data. Therefore, as a preliminary approach experiments in SCW-cooled bare tubes and in bundles cooled with SC modeling fluids can be used. One of the SC modeling fluids typically used is Freon-12 (R-12) where the critical pressure is 4.136 MPa and the critical temperature is 111.97ºC. These conditions correspond to a critical pressure of 22.064 MPa and critical temperature of 373.95ºC in water. A set of experimental data obtained in a Freon-12 cooled vertical bare bundle at the Institute of Physics and Power Engineering (IPPE, Obninsk, Russia) was analyzed. This set consisted of 20 cases of a vertically oriented 7-element bundle installed in a hexagonal flow channel. To secure the bundle in the flow channel 3 thin spacers were used. The dataset was obtained at equivalent parameters of the proposed SCWR concepts. Data was collected at pressures of about 4.65 MPa for several different combinations of wall and bulk-fluid temperatures that were below, at, or above the pseudocritical temperature. Heat fluxes ranged from 9 kW/m2 to 120 kW/m2 and mass fluxes ranged from 440 kg/m2s to 1320 kg/m2s. Also inlet temperatures ranged from 70ºC – 120ºC. The test section consisted of fuel elements that were 9.5 mm in diameter with the total heated length of 1 m. Bulk-fluid and wall temperature profiles were recorded using a combination of 8 different thermocouples.The data was analyzed with respect to its temperature profile and heat transfer coefficient along the heated length of the test section. In a previous study it was confirmed that there is the existence of three distinct regimes for forced convention with supercritical fluids. (1) Normal heat transfer; (2) Deteriorated heat transfer, characterized by higher than expected temperatures; and (3) Improved heat transfer, characterized by lower than expected temperatures. All three regions were observed for the 7 rod bundle experiments. This work compares the experimental data to predictions based upon current 1-D correlations for heat transfer in supercritical fluids. Results show that no current 1-D correlation was able to accurately predict heat transfer coefficients within ±50%. A parametric analysis of the data was also completed to determine if continuity in the experiment was present. Results of this study show that two distinct regions are present in the data. For cases with a mass flux below 1200 kg/m2s wall temperature profiles appear to be normal while in cases with mass flux above 1200 kg/m2s temperature given by the wall thermocouples were higher than normal. This phenomenon occurred regardless of heat flux-to-mass flux ratios. / UOIT

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.

Courses in analytical mechanics for undergraduate students are often limited to treatment of holonomic constraints, which are constraints on coordinates. The concept of nonholonomic constraints, constraints on velocities, is usually only mentioned briefly and it is easy to get a wrongful idea of what they are and how to treat them. This text explains and compares the methods of deriving the Euler-Lagrange equations and the consequences when imposing different kinds of constraints. One way to properly treat both holonomic and nonholonomic constraints is given, pinpointing the difficulties and common errors. Along the way, the treatment in local coordinates is also put in more modern terms, in the language of differential geometry, which is the language most commonly used in modern texts on the subject.

This thesis explores efficient techniques for generating 3D reconstructions from imagery. Non-linear optimization is one of the core techniques used when computing a reconstruction and is a computational bottleneck for large sets of images. Since non-linear optimization requires a good initialization to avoid getting stuck in local minima, robust systems for generating reconstructions from images build up the reconstruction incrementally. A hierarchical approach is to split up the images into small subsets, reconstruct each subset independently and then hierarchically merge the subsets. Rigidly locking together portions of the reconstructions reduces the number of parameters needed to represent them when merging, thereby lowering the computational cost of the optimization. We present two techniques that involve optimizing with parts of the reconstruction rigidly locked together. In the first, we start by rigidly grouping the cameras and scene features from each of the reconstructions being merged into separate groups. Cameras and scene features are then incrementally unlocked and optimized until the reconstruction is close to the minimum energy. This technique is most effective when the influence of the new measurements is restricted to a small set of parameters. Measurements that stitch together weakly coupled portions of the reconstruction, though, tend to cause deformations in the low error modes of the reconstruction and cannot be efficiently incorporated with the previous technique. To address this, we present a spectral technique for clustering the tightly coupled portions of a reconstruction into rigid groups. Reconstructions partitioned in this manner can closely mimic the poorly conditioned, low error modes, and therefore efficiently incorporate measurements that stitch together weakly coupled portions of the reconstruction. We explain how this technique can be used to scalably and efficiently generate reconstructions from large sets of images.

Experiments investigating complex flows in rod bundles with spacer grids that have mixing devices (such as flow mixing vanes) have mostly been performed using single-point measurements. Although these measurements allow local comparisons of experimental and numerical data they provide little insight because the discrepancies can be due to the integrated effects of many complex flow phenomena such as wake-wake, wake-vane, and vane-boundary layer interactions occurring simultaneously in a complex flow environment. In order to validate the simulations results, detailed comparison with experimental data must be done. This work describes an experimental database obtained using Time Resolved Particle Image Velocimetry (TR-PIV) measurements within a 5 x 5 rod bundle with spacer-grids. Measurements were performed using two different grid designs. One typical of Boiling Water Reactors (BWR) with swirl type mixing vanes and the other typical of Pressurized Water Reactors (PWR) with split type mixing vanes. High quality data was obtained in the vicinity of the grid using the multi-scale approach. One of the unique characteristic of this set-up is the use of the Matched Index of Refraction (MIR) technique employed in this investigation. This approach allows the use of high temporal and spatial non-intrusive dynamic measurement techniques to investigate the flow evolution below and immediately above the spacer. The experimental data presented includes explanation of the various cases tested such as test rig dimensions, measurement zones, the test equipment and the boundary conditions in order to provide appropriate data for comparison with Computational Fluid Dynamics (CFD) simulations. Turbulence parameters of the obtained data are analyzed in order to gain insight of the physical phenomena. The shape of the velocity profile at various distances from the spacer show important modifications passing the grid which delineates the significant effects of the presence of the grid spacer. Influence of the vanes wake in the global velocity was quantified to be up to a distance of 4 hydraulic diameters from the edge of the grid.Spatial and temporal correlations in the two measured dimensions were performed to quantify the time and length scales present in the flow in the vicinity of the grids and its influence in the flow modification induced by the vanes. Detection of vortex cores was performed using the vorticity, swirl strength and Galilean decomposition approach. The resulted cores were then tracked in time, in order to observe the evolution of the structures under the influence of the vanes for each grid. Vortex stretching was quantified in order to gain insight of the energy dissipation process normally associated with the phenomena. This work presents data in a single-phase flow situation and an analysis of these data for understanding complex flow structure. This data provide for the first time detailed temporal velocity full field which can be used to validate CFD codes.