Interventions based on self-management of well-being theory:Pooling data to demonstrate mediation and ceiling effects, and to compare formats

Objectives: Interventions based on self-management of well-being (SMW) theory have shown positive effects, but additional questions remain: (1) Are improvements in well-being, as induced by the interventions, mediated by improved self-management ability (SMA)? (2) Do the interventions show ceiling effects? (3) Is a particular format of SMW intervention (individual, group, or self-help) more effective?Method: Data of three randomized controlled trials were pooled. The greater part of the sample (N = 445) consisted of single older females. A bootstrap analysis was performed to test for mediation. Regression analyses with interaction effects were performed to test for ceiling effects. Controlled and transformed effect sizes (proportion of maximum change) were calculated to compare formats.Results: There was a full significant mediation of well-being by SMA. A significant interaction (ceiling) effect was found on well-being, but not on SMA. The controlled effect sizes of the raw scores were small to medium (.04-.49), and were small to large after transformation (.41-.73). None of the intervention formats was more effective.Conclusion: Support for SMW theory was found, i.e. increasing self-management ability lead to improved well-being. Some ceiling effect was found. We conclude that various SMW interventions formats can improve self-management abilities and well-being with medium effects

Distress and mental health care and medication use among survivors of multiple primary cancer diagnoses:Findings from the 2016 National Health Interview Survey

Objective: Over 1 million survivors of multiple primary cancer (MPC) diagnoses reside in the USA. Information regarding their physical and mental health status is limited. This study examined distress and mental health care use among MPC survivors relative to survivors of a single primary cancer (SPC) diagnosis. Methods: Using the 2016 National Health Information Survey, MPC survivors (n = 265), SPC survivors (n = 2103), and no cancer controls (NCC; n = 28,320) were identified. The MPC group was compared to the SPC and NCC groups with regard to multiple distress indices and use of mental health care and anxiety and depression medication. Results: Relative to the SPC group, the MPC group reported more Total Distress (M = 9.59 vs. 8.84; p < .001), and were more likely to report daily or weekly anxiety feelings (OR = 2.07; p < .001), meet criteria for serious psychological distress (OR = 1.49; p = .02) and have talked to a mental health professional (OR = 1.75; p = .01). Comparison of MPC and NweCC groups yielded similar results. The MPC group did not differ from the SPC or NCC groups in severity of anxiety or depression feelings, distress interference, or anxiety and depression medication use. Conclusions: MPC survivors reported greater distress relative to SPC survivors. The clinical significance of this greater distress is unclear, however. While MPC survivors were more likely to have talked to a mental health professional, uptake of mental health care appeared to be suboptimal. MPC and SPC survivors might be considered distinct subgroups and increased attention devoted to potentially unique mental and physical health needs of MPC survivors

Spatial Hearing with Simultaneous Sound Sources: A Psychophysical Investigation

This thesis provides an overview of work conducted to investigate human spatial hearing in situations involving multiple concurrent sound sources. Much is known about spatial hearing with single sound sources, including the acoustic cues to source location and the accuracy of localisation under different conditions. However, more recently interest has grown in the behaviour of listeners in more complex environments. Concurrent sound sources pose a particularly difficult problem for the auditory system, as their identities and locations must be extracted from a common set of sensory receptors and shared computational machinery. It is clear that humans have a rich perception of their auditory world, but just how concurrent sounds are processed, and how accurately, are issues that are poorly understood. This work attempts to fill a gap in our understanding by systematically examining spatial resolution with multiple sound sources. A series of psychophysical experiments was conducted on listeners with normal hearing to measure performance in spatial localisation and discrimination tasks involving more than one source. The general approach was to present sources that overlapped in both frequency and time in order to observe performance in the most challenging of situations. Furthermore, the role of two primary sets of location cues in concurrent source listening was probed by examining performance in different spatial dimensions. The binaural cues arise due to the separation of the two ears, and provide information about the lateral position of sound sources. The spectral cues result from location-dependent filtering by the head and pinnae, and allow vertical and front-rear auditory discrimination. Two sets of experiments are described that employed relatively simple broadband noise stimuli. In the first of these, two-point discrimination thresholds were measured using simultaneous noise bursts. It was found that the pair could be resolved only if a binaural difference was present; spectral cues did not appear to be sufficient. In the second set of experiments, the two stimuli were made distinguishable on the basis of their temporal envelopes, and the localisation of a designated target source was directly examined. Remarkably robust localisation was observed, despite the simultaneous masker, and both binaural and spectral cues appeared to be of use in this case. Small but persistent errors were observed, which in the lateral dimension represented a systematic shift away from the location of the masker. The errors can be explained by interference in the processing of the different location cues. Overall these experiments demonstrated that the spatial perception of concurrent sound sources is highly dependent on stimulus characteristics and configurations. This suggests that the underlying spatial representations are limited by the accuracy with which acoustic spatial cues can be extracted from a mixed signal. Three sets of experiments are then described that examined spatial performance with speech, a complex natural sound. The first measured how well speech is localised in isolation. This work demonstrated that speech contains high-frequency energy that is essential for accurate three-dimensional localisation. In the second set of experiments, spatial resolution for concurrent monosyllabic words was examined using similar approaches to those used for the concurrent noise experiments. It was found that resolution for concurrent speech stimuli was similar to resolution for concurrent noise stimuli. Importantly, listeners were limited in their ability to concurrently process the location-dependent spectral cues associated with two brief speech sources. In the final set of experiments, the role of spatial hearing was examined in a more relevant setting containing concurrent streams of sentence speech. It has long been known that binaural differences can aid segregation and enhance selective attention in such situations. The results presented here confirmed this finding and extended it to show that the spectral cues associated with different locations can also contribute. As a whole, this work provides an in-depth examination of spatial performance in concurrent source situations and delineates some of the limitations of this process. In general, spatial accuracy with concurrent sources is poorer than with single sound sources, as both binaural and spectral cues are subject to interference. Nonetheless, binaural cues are quite robust for representing concurrent source locations, and spectral cues can enhance spatial listening in many situations. The findings also highlight the intricate relationship that exists between spatial hearing, auditory object processing, and the allocation of attention in complex environments

The Bigger Picture:Research Strategy for a Photo-Elicitation Study Investigating Positive Health Perceptions of Older Adults With Low Socioeconomic Status

Research focussing on older adults of low socioeconomic status (SES) faces several methodological challenges, including high rates of non-response and drop-out. In addition, older adults of low SES tend to be less willing to participate in research and are more likely to experience cognitive impairments and literacy problems. Photo-elicitation studies do not require high levels of literacy, and they might therefore be suitable for use in research with older adults of low SES. To date, however, little is known about setting up such studies with this target group. Our aim was to demonstrate how we systematically set up a researcher-driven photo-elicitation study to generate greater insight into the positive health perceptions of older adults of low SES. Our strategy consisted of three phases: development, testing and execution. In this article, we discuss each step of the research strategy and describe the limitations and strengths of our study. We also formulate recommendations for further research using photo-elicitation methods with this target group. Based on the results of this study, we conclude that the use of researcher-driven photo-elicitation is a powerful tool for enhancing understanding with regard to positive health perceptions and experiences of older adults of low SES. The usefulness of the method is particularly dependent on the careful development and testing of the study

Protein Design Based on a PHD Scaffold

The plant homeodomain (PHD) is a protein domain of ~45�100 residues characterised by a Cys4-His-Cys3 zinc-binding motif. When we commenced our study of the PHD in 2000, it was clear that the domain was commonly found in proteins involved in transcription. Sequence alignments indicate that while the cysteines, histidine and a few other key residues are strictly conserved, the rest of the domain varies greatly in terms of both amino acid composition and length. However, no structural information was available on the PHD and little was known about its function. We were therefore interested in determining the structure of a PHD in the hope that this might shed some light on its function and molecular mechanism of action. Our work began with the structure determination of a representative PHD, Mi2b-P2, and this work is presented in Chapter 3. Through comparison of this structure with the two other PHD structures that were determined during the course of our work, it became clear that PHDs adopt a well-defined globular fold with a superimposable core region. In addition, PHDs contain two loop regions (termed L1 and L3) that display increased flexibility and overlay less well between the three PHD structures available. These L1 and L3 regions correspond to variable regions identified earlier in PHD sequence alignments, indicating that L1 and L3 are probably not crucial for the PHD fold, but are instead likely to be responsible for imparting function(s) to the PHD. Indeed, numerous recent functional studies of PHDs from different proteins have since demonstrated their ability in binding a range of other proteins. In order to ascertain whether or not L1 and L3 were in fact dispensable for folding, we made extensive mutations (including both insertions and substitutions) in the loop regions of Mi2b-P2 and showed that the structure was maintained. We then went on to illustrate that a new function could be imparted to Mi2b-P2 by inserting a five-residue CtBP-binding motif into the L1 region and showed this chimera could fold and bind CtBP. Having established that the PHD could adopt a new binding function, we next sought to use combinatorial methods to introduce other novel functions into the PHD scaffold. Phage display was selected for this purpose, because it is a well-established technique and has been used successfully to engineer zinc-binding domains by other researchers. However, in order to establish this technique in our laboratory, we first chose a control system in which two partner proteins were already known to interact in vitro. We chose the protein complex formed between the transcriptional regulators LMO2 and ldb1 as a test case. We have examined this interaction in detail in our laboratory, and determined its three-dimensional structure. Furthermore, inappropriate formation of this complex is implicated in the onset of T-cell acute lymphoblastic leukemia. We therefore sought to use phage display to engineer ldb1 mimics that could potentially compete against wild-type ldb1 for LMO2, and this work is described in Chapter 4. Using a phage library containing ~3 x 10 7 variants of the LMO2-binding region of ldb1, we isolated mutants that were able to interact with LMO2 with higher affinity and specificity than wild-type ldb1. These ldb1 mutants represent a first step towards finding potential therapeutics for treating LMO-associated diseases. Having established phage display in our laboratory, we went on to search for PHD mutants that could bind selected target proteins. This work is described in Chapter 5. We created three PHD libraries with eight randomized residues in each of L1, L3 or in both loops of the PHD. These PHD libraries were then screened against four target proteins. After four rounds of selection, we were able to isolate a PHD mutant (dubbed L13-FH6) that could bind our test protein Fli-ets. This result demonstrates that a novel function can be imparted to the PHD using combinatorial methods and opens the way for further work in applying the PHD scaffold to other protein design work. In summary, the work detailed in Chapters 3 and 5 demonstrates that the PHD possesses many of the properties that are desirable for a protein scaffold for molecular recognition, including small size, stability, and a well-characterised structure. Moreover, the PHD motif possesses two loops (L1 and L3) of substantial size that can be remodeled for target binding. This may lead to an enhancement of binding affinities and specificities over other small scaffolds that have only one variable loop. In light of the fact that PHDs are mainly found in nuclear proteins, it is reasonable to expect that engineered PHDs could be expressed and function in an intracellular environment, unlike many other scaffolds that can only function in an oxidizing environment. Therefore, our results together with other currently available genomic and functional information indicate PHD is an excellent candidate for a scaffold that could be used to modify cellular processes. Appendices 1 and 2 describe completed bodies of work on unrelated projects that I have carried out during the course of my PhD candidature. The first comprises the invention and application of DNA sequences that contain all N-base sequences in the minimum possible length. This work is presented as a reprint of our recently published paper in Nucleic Acids Research. The second Appendix describes our structural analysis of an antifreeze protein from the shorthorn sculpin, a fish that lives in the Arctic and Antarctic oceans. This work is presented as a manuscript that is currently under review at the Journal of the American Chemical Society

Centaur 1952

Digitised by the Faculty of the Veterinary Scienc