Evaluation of the Heart of Birmingham teaching Primary Care Trust (HoBtPCT): My Choice Weight Management Programme:report commissioned by Heart of Birmingham teaching Primary Care Trust

This report details an evaluation of the My Choice Weight Management Programme undertaken by a research team from the School of Pharmacy at Aston University. The My Choice Weight Management Programme is delivered through community pharmacies and general practitioners (GPs) contracted to provide services by the Heart of Birmingham teaching Primary Care Trust. It is designed to support individuals who are ‘ready to change’ by enabling the individual to work with a trained healthcare worker (for example, a healthcare assistant, practice nurse or pharmacy assistant) to develop a care plan designed to enable the individual to lose 5-10% of their current weight. The Programme aims to reduce adult obesity levels; improve access to overweight and obesity management services in primary care; improve diet and nutrition; promote healthy weight and increased levels of physical activity in overweight or obese patients; and support patients to make lifestyle changes to enable them to lose weight. The Programme is available for obese patients over 18 years old who have a Body Mass Index (BMI) greater than 30 kg/m2 (greater than 25 kg/m2 in Asian patients) or greater than 28 kg/m2 (greater than 23.5 kg/m2 in Asian patients) in patients with co-morbidities (diabetes, high blood pressure, cardiovascular disease). Each participant attends weekly consultations over a twelve session period (the final iteration of these weekly sessions is referred to as ‘session twelve’ in this report). They are then offered up to three follow up appointments for up to six months at two monthly intervals (the final of these follow ups, taking place at approximately nine months post recruitment, is referred to as ‘session fifteen’ in this report). A review of the literature highlights the dearth of published research on the effectiveness of primary care- or community-based weight management interventions. This report may help to address this knowledge deficit. A total of 451 individuals were recruited on to the My Choice Weight Management Programme. More participants were recruited at GP surgeries (n=268) than at community pharmacies (n=183). In total, 204 participants (GP n=102; pharmacy n=102) attended session twelve and 82 participants (GP n=22; pharmacy 60) attended session fifteen. The unique demographic characteristics of My Choice Weight Management Programme participants – participants were recruited from areas with high levels of socioeconomic deprivation and over four-fifths of participants were from Black and Minority Ethnic groups; populations which are traditionally underserved by healthcare interventions – make the achievements of the Programme particularly notable. The mean weight loss at session 12 was 3.8 kg (equivalent to a reduction of 4.0% of initial weight) among GP surgery participants and 2.4 kg (2.8%) among pharmacy participants. At session 15 mean weight loss was 2.3 kg (2.2%) among GP surgery participants and 3.4 kg (4.0%) among pharmacy participants. The My Choice Weight Management Programme improved the general health status of participants between recruitment and session twelve as measured by the validated SF-12 questionnaire. While cost data is presented in this report, it is unclear which provider type delivered the Programme more cost-effectively. Attendance rates on the Programme were consistently better among pharmacy participants than among GP participants. The opinions of programme participants (both those who attended regularly and those who failed to attend as expected) and programme providers were explored via semi-structured interviews and, in the case of the participants, a selfcompletion postal questionnaire. These data suggest that the Programme was almost uniformly popular with both the deliverers of the Programme and participants on the Programme with 83% of questionnaire respondents indicating that they would be happy to recommend the Programme to other people looking to lose weight. Our recommendations, based on the evidence provided in this report, include: a. Any consideration of an extension to the study also giving comparable consideration to an extension of the Programme evaluation. The feasibility of assigning participants to a pharmacy provider or a GP provider via a central allocation system should also be examined. This would address imbalances in participant recruitment levels between provider type and allow for more accurate comparison of the effectiveness in the delivery of the Programme between GP surgeries and community pharmacies by increasing the homogeneity of participants at each type of site and increasing the number of Programme participants overall. b. Widespread dissemination of the findings from this review of the My Choice Weight Management Project should be undertaken through a variety of channels. c. Consideration of the inclusion of the following key aspects of the My Choice Weight Management Project in any extension to the Programme: i. The provision of training to staff in GP surgeries and community pharmacies responsible for delivery of the Programme prior to patient recruitment. ii. Maintaining the level of healthcare staff input to the Programme. iii. The regular schedule of appointments with Programme participants. iv. The provision of an increased variety of printed material. d. A simplification of the data collection method used by the Programme commissioners at the individual Programme delivery sites.

An alternating boundary integral based method for a Cauchy problem for the Laplace equation in semi-infinite regions

We consider a Cauchy problem for the Laplace equation in a two-dimensional semi-infinite region with a bounded inclusion, i.e. the region is the intersection between a half-plane and the exterior of a bounded closed curve contained in the half-plane. The Cauchy data are given on the unbounded part of the boundary of the region and the aim is to construct the solution on the boundary of the inclusion. In 1989, Kozlov and Maz'ya [10] proposed an alternating iterative method for solving Cauchy problems for general strongly elliptic and formally self-adjoint systems in bounded domains. We extend their approach to our setting and in each iteration step mixed boundary value problems for the Laplace equation in the semi-infinite region are solved. Well-posedness of these mixed problems are investigated and convergence of the alternating procedure is examined. For the numerical implementation an efficient boundary integral equation method is proposed, based on the indirect variant of the boundary integral equation approach. The mixed problems are reduced to integral equations over the (bounded) boundary of the inclusion. Numerical examples are included showing the feasibility of the proposed method.

An iterative method based on boundary integrals for elliptic Cauchy problems in semi-infinite domains

In this study, we investigate the problem of reconstruction of a stationary temperature field from given temperature and heat flux on a part of the boundary of a semi-infinite region containing an inclusion. This situation can be modelled as a Cauchy problem for the Laplace operator and it is an ill-posed problem in the sense of Hadamard. We propose and investigate a Landweber-Fridman type iterative method, which preserve the (stationary) heat operator, for the stable reconstruction of the temperature field on the boundary of the inclusion. In each iteration step, mixed boundary value problems for the Laplace operator are solved in the semi-infinite region. Well-posedness of these problems is investigated and convergence of the procedures is discussed. For the numerical implementation of these mixed problems an efficient boundary integral method is proposed which is based on the indirect variant of the boundary integral approach. Using this approach the mixed problems are reduced to integral equations over the (bounded) boundary of the inclusion. Numerical examples are included showing that stable and accurate reconstructions of the temperature field on the boundary of the inclusion can be obtained also in the case of noisy data. These results are compared with those obtained with the alternating iterative method.

Weight loss strategies, stress, and cognitive function:supervised versus unsupervised dieting

The early stages of dieting to lose weight have been associated with neuro-psychological impairments. Previous work has not elucidated whether these impairments are a function solely of unsupported or supported dieting. Raised cortico-steroid levels have been implicated as a possible causal mechanism. Healthy, overweight, pre-menopausal women were randomised to one of three conditions in which they dieted either as part of a commercially available weight loss group, dieted without any group support or acted as non-dieting controls for 8 weeks. Testing occurred at baseline and at 1, 4 and 8 weeks post baseline. During each session, participants completed measures of simple reaction time, motor speed, vigilance, immediate verbal recall, visuo-spatial processing and (at Week 1 only) executive function. Cortisol levels were gathered at the beginning and 30 min into each test session, via saliva samples. Also, food intake was self-recorded prior to each session and fasting body weight and percentage body fat were measured at each session. Participants in the unsupported diet condition displayed poorer vigilance performance (p=0.001) and impaired executive planning function (p=0.013) (along with a marginally significant trend for poorer visual recall (p=0.089)) after 1 week of dieting. No such impairments were observed in the other two groups. In addition, the unsupported dieters experienced a significant rise in salivary cortisol levels after 1 week of dieting (p<0.001). Both dieting groups lost roughly the same amount of body mass (p=0.011) over the course of the 8 weeks of dieting, although only the unsupported dieters experienced a significant drop in percentage body fat over the course of dieting (p=0.016). The precise causal nature of the relationship between stress, cortisol, unsupported dieting and cognitive function is, however, uncertain and should be the focus of further research. © 2005 Elsevier Ltd. All rights reserved.

Some Computational Aspects of the Consistent Mass Finite Element Method for a (semi-)periodic Eigenvalue Problem

We consider a model eigenvalue problem (EVP) in 1D, with periodic or semi–periodic boundary conditions (BCs). The discretization of this type of EVP by consistent mass finite element methods (FEMs) leads to the generalized matrix EVP Kc = λ M c, where K and M are real, symmetric matrices, with a certain (skew–)circulant structure. In this paper we fix our attention to the use of a quadratic FE–mesh. Explicit expressions for the eigenvalues of the resulting algebraic EVP are established. This leads to an explicit form for the approximation error in terms of the mesh parameter, which confirms the theoretical error estimates, obtained in [2].

A Method for Testing Object Localization as a Function of Eod Amplitude in the Weakly Electric Fish Brachyhypopomus Pinnicaudatus

I would like to thank Dr. Philip Stoddard for his patience and guidance throughout the past four years. He has not only taught me about behavior and electricity, but he has also taught me how to think scientifically. Vielka Salazar for making herself available to answer my questions and to help me with my projects. Montserrat Alfaro for providing me with support under times of frustration. Fabian A. Pal, who has often made himself available when I needed help to finish my projects, for being supportive, and for believing in me and my abilities. Most importantly, I would like to thank my parents who have shown tremendous support and patience during the past years. I would also like to thank the Honors Committee, specially Dr. Richards for taking the time to review my thesis and helping me modify it. Finally, I would like to thank the MARC program for providing me with financial assistance and the opportunity to perform this project.

Enzymatic Polymerization of High Molecular Weight DNA

The use of DNA as a polymeric building material transcends its function in biology and is exciting in bionanotechnology for applications ranging from biosensing, to diagnostics, and to targeted drug delivery. These applications are enabled by DNA’s unique structural and chemical properties, embodied as a directional polyanion that exhibits molecular recognition capabilities. Hence, the efficient and precise synthesis of high molecular weight DNA materials has become key to advance DNA bionanotechnology. Current synthesis methods largely rely on either solid phase chemical synthesis or template-dependent polymerase amplification. The inherent step-by-step fashion of solid phase synthesis limits the length of the resulting DNA to typically less than 150 nucleotides. In contrast, polymerase based enzymatic synthesis methods (e.g., polymerase chain reaction) are not limited by product length, but require a DNA template to guide the synthesis. Furthermore, advanced DNA bionanotechnology requires tailorable structural and self-assembly properties. Current synthesis methods, however, often involve multiple conjugating reactions and extensive purification steps.

The research described in this dissertation aims to develop a facile method to synthesize high molecular weight, single stranded DNA (or polynucleotide) with versatile functionalities. We exploit the ability of a template-independent DNA polymerase−terminal deoxynucleotidyl transferase (TdT) to catalyze the polymerization of 2’-deoxyribonucleoside 5’-triphosphates (dNTP, monomer) from the 3’-hydroxyl group of an oligodeoxyribonucleotide (initiator). We termed this enzymatic synthesis method: TdT catalyzed enzymatic polymerization, or TcEP.

Specifically, this dissertation is structured to address three specific research aims. With the objective to generate high molecular weight polynucleotides, Specific Aim 1 studies the reaction kinetics of TcEP by investigating the polymerization of 2’-deoxythymidine 5’-triphosphates (monomer) from the 3’-hydroxyl group of oligodeoxyribothymidine (initiator) using in situ 1H NMR and fluorescent gel electrophoresis. We found that TcEP kinetics follows the “living” chain-growth polycondensation mechanism, and like in “living” polymerizations, the molecular weight of the final product is determined by the starting molar ratio of monomer to initiator. The distribution of the molecular weight is crucially influenced by the molar ratio of initiator to TdT. We developed a reaction kinetics model that allows us to quantitatively describe the reaction and predict the molecular weight of the reaction products.

Specific Aim 2 further explores TcEP’s ability to transcend homo-polynucleotide synthesis by varying the choices of initiators and monomers. We investigated the effects of initiator length and sequence on TcEP, and found that the minimum length of an effective initiator should be 10 nucleotides and that the formation of secondary structures close to the 3’-hydroxyl group can impede the polymerization reaction. We also demonstrated TcEP’s capacity to incorporate a wide range of unnatural dNTPs into the growing chain, such as, hydrophobic fluorescent dNTP and fluoro modified dNTP. By harnessing the encoded nucleotide sequence of an initiator and the chemical diversity of monomers, TcEP enables us to introduce molecular recognition capabilities and chemical functionalities on the 5’-terminus and 3’-terminus, respectively.

Building on TcEP’s synthesis capacities, in Specific Aim 3 we invented a two-step strategy to synthesize diblock amphiphilic polynucleotides, in which the first, hydrophilic block serves as a macro-initiator for the growth of the second block, comprised of natural and/or unnatural nucleotides. By tuning the hydrophilic length, we synthesized the amphiphilic diblock polynucleotides that can self-assemble into micellar structures ranging from star-like to crew-cut morphologies. The observed self-assembly behaviors agree with predictions from dissipative particle dynamics simulations as well as scaling law for polyelectrolyte block copolymers.

In summary, we developed an enzymatic synthesis method (i.e., TcEP) that enables the facile synthesis of high molecular weight polynucleotides with low polydispersity. Although we can control the nucleotide sequence only to a limited extent, TcEP offers a method to integrate an oligodeoxyribonucleotide with specific sequence at the 5’-terminus and to incorporate functional groups along the growing chains simultaneously. Additionally, we used TcEP to synthesize amphiphilic polynucleotides that display self-assemble ability. We anticipate that our facile synthesis method will not only advance molecular biology, but also invigorate materials science and bionanotechnology.

Simulation of Oil Shale Semi-Coke Particle Cold Transportation in a Spouted Bed Using CPFD Method

The spouted bed was widely used due to its good mixing of particles and effective phase transferability between the gas and solid phase. In this paper, the transportation process of particles in a 3D spouted bed was studied using the Computational Particle Fluid Dynamics (CPFD) numerical method. Experiments were conducted to verify the validity of the simulation results. Distributions of the pressure, velocities and particle concentration of transportation devices were investigated. The motion state and characteristics of multiphase flows in the transportation device were demonstrated under various operating conditions. The results showed that a good consistency was obtained between the simulated results and the experimental results. The motion characteristics of the gas-solid two-phase flow in the device was effectively predicted, which could assist the optimal operating condition estimation for the spouted transportation process.

Photoionization of Co+ and electron-impact excitation of Co2 + using the Dirac R-matrix method

Modelling of massive stars and supernovae (SNe) plays a crucial role in understanding galaxies. From this modelling we can derive fundamental constraints on stellar evolution, mass-loss processes, mixing, and the products of nucleosynthesis. Proper account must be taken of all important processes that populate and depopulate the levels (collisional excitation, de-excitation, ionization, recombination, photoionization, bound–bound processes). For the analysis of Type Ia SNe and core collapse SNe (Types Ib, Ic and II) Fe group elements are particularly important. Unfortunately little data is currently available and most noticeably absent are the photoionization cross-sections for the Fe-peaks which have high abundances in SNe. Important interactions for both photoionization and electron-impact excitation are calculated using the relativistic Dirac atomic R-matrix codes (DARC) for low-ionization stages of Cobalt. All results are calculated up to photon energies of 45 eV and electron energies up to 20 eV. The wavefunction representation of Co III has been generated using GRASP0 by including the dominant 3d⁷, 3d⁶[4s, 4p], 3p⁴3d⁹ and 3p⁶3d⁹ configurations, resulting in 292 fine structure levels. Electron-impact collision strengths and Maxwellian averaged effective collision strengths across a wide range of astrophysically relevant temperatures are computed for Co III. In addition, statistically weighted level-resolved ground and metastable photoionization cross-sections are presented for Co II and compared directly with existing work.

A semi-Lagrangian finite volume method for solving viscoelastic flow problems

Recently, there has been considerable interest in solving viscoelastic problems in 3D particularly with the improvement in modern computing power. In many applications the emphasis has been on economical algorithms which can cope with the extra complexity that the third dimension brings. Storage and computer time are of the essence. The advantage of the finite volume formulation is that a large amount of memory space is not required. Iterative methods rather than direct methods can be used to solve the resulting linear systems efficiently.

A method to determine the impact of visual function on lesion detection performance

There are few professions in which visual acuity is as important as it is to radiologists. The diagnostic decision making process is composed of a number of events (detection or observation, interpretation and reporting), where the detection phase is subject to a number of physical and psychological phenomena that are critical to the process. Visual acuity is one phenomenon that has often been overlooked, and there is very little research assessing the impact of reduced visual acuity on diagnostic performance. The aim of this study was to investigate the impact of reduced visual acuity on an observer’s ability to detect simulated nodules in an anthropomorphic chest phantom.

A method to determine the impact of reduced visual function on nodule detection performance

Purpose - In this study we aim to validate a method to assess the impact of reduced visual function and observer performance concurrently with a nodule detection task. Materials and methods - Three consultant radiologists completed a nodule detection task under three conditions: without visual defocus (0.00 Dioptres; D), and with two different magnitudes of visual defocus (−1.00 D and −2.00 D). Defocus was applied with lenses and visual function was assessed prior to each image evaluation. Observers evaluated the same cases on each occasion; this comprised of 50 abnormal cases containing 1–4 simulated nodules (5, 8, 10 and 12 mm spherical diameter, 100 HU) placed within a phantom, and 25 normal cases (images containing no nodules). Data was collected under the free-response paradigm and analysed using Rjafroc. A difference in nodule detection performance would be considered significant at p < 0.05. Results - All observers had acceptable visual function prior to beginning the nodule detection task. Visual acuity was reduced to an unacceptable level for two observers when defocussed to −1.00 D and for one observer when defocussed to −2.00 D. Stereoacuity was unacceptable for one observer when defocussed to −2.00 D. Despite unsatisfactory visual function in the presence of defocus we were unable to find a statistically significant difference in nodule detection performance (F(2,4) = 3.55, p = 0.130). Conclusion - A method to assess visual function and observer performance is proposed. In this pilot evaluation we were unable to detect any difference in nodule detection performance when using lenses to reduce visual function.

Estimation of whole body muscle, adipose/fat mass, validation in health and during weight loss. Development of prediction equations using MRI as reference method

Background: Body composition is affected by diseases, and affects responses to medical treatments, dosage of medicines, etc., while an abnormal body composition contributes to the causation of many chronic diseases. While we have reliable biochemical tests for certain nutritional parameters of body composition, such as iron or iodine status, and we have harnessed nuclear physics to estimate the body’s content of trace elements, the very basic quantification of body fat content and muscle mass remains highly problematic. Both body fat and muscle mass are vitally important, as they have opposing influences on chronic disease, but they have seldom been estimated as part of population health surveillance. Instead, most national surveys have merely reported BMI and waist, or sometimes the waist/hip ratio; these indices are convenient but do not have any specific biological meaning. Anthropometry offers a practical and inexpensive method for muscle and fat estimation in clinical and epidemiological settings; however, its use is imperfect due to many limitations, such as a shortage of reference data, misuse of terminology, unclear assumptions, and the absence of properly validated anthropometric equations. To date, anthropometric methods are not sensitive enough to detect muscle and fat loss. Aims: The aim of this thesis is to estimate Adipose/fat and muscle mass in health disease and during weight loss through; 1. evaluating and critiquing the literature, to identify the best-published prediction equations for adipose/fat and muscle mass estimation; 2. to derive and validate adipose tissue and muscle mass prediction equations; and 3.to evaluate the prediction equations along with anthropometric indices and the best equations retrieved from the literature in health, metabolic illness and during weight loss. Methods: a Systematic review using Cochrane Review method was used for reviewing muscle mass estimation papers that used MRI as the reference method. Fat mass estimation papers were critically reviewed. Mixed ethnic, age and body mass data that underwent whole body magnetic resonance imaging to quantify adipose tissue and muscle mass (dependent variable) and anthropometry (independent variable) were used in the derivation/validation analysis. Multiple regression and Bland-Altman plot were applied to evaluate the prediction equations. To determine how well the equations identify metabolic illness, English and Scottish health surveys were studied. Statistical analysis using multiple regression and binary logistic regression were applied to assess model fit and associations. Also, populations were divided into quintiles and relative risk was analysed. Finally, the prediction equations were evaluated by applying them to a pilot study of 10 subjects who underwent whole-body MRI, anthropometric measurements and muscle strength before and after weight loss to determine how well the equations identify adipose/fat mass and muscle mass change. Results: The estimation of fat mass has serious problems. Despite advances in technology and science, prediction equations for the estimation of fat mass depend on limited historical reference data and remain dependent upon assumptions that have not yet been properly validated for different population groups. Muscle mass does not have the same conceptual problems; however, its measurement is still problematic and reference data are scarce. The derivation and validation analysis in this thesis was satisfactory, compared to prediction equations in the literature they were similar or even better. Applying the prediction equations in metabolic illness and during weight loss presented an understanding on how well the equations identify metabolic illness showing significant associations with diabetes, hypertension, HbA1c and blood pressure. And moderate to high correlations with MRI-measured adipose tissue and muscle mass before and after weight loss. Conclusion: Adipose tissue mass and to an extent muscle mass can now be estimated for many purposes as population or groups means. However, these equations must not be used for assessing fatness and categorising individuals. Further exploration in different populations and health surveys would be valuable.

Weight loss improves biomarkers endothelial function and systemic inflammation in obese postmenopausal Saudi women.

Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function and systemic inflammation response to weight loss in obese postmenopausal Saudi women. Material and methods: Eighty postmenopausal obese Saudi women (mean age 52.64±6.13 year) participated in two groups: Group (A) received aerobic exercise on treadmill and diet whereas, group (B) received no intervention. Markers of inflammation and endothelial function were measured before and after 3 months at the end of the study. Results: The values of body mass index(BMI), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and plasminogen activator inhibitor- 1 activity (PAI-1:Ac) were significantly decreased in group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. Conclusion: Weight loss ameliorates inflammatory cytokines and markers of endothelial function in obese postmenopausal Saudi women.