Can we improve the early diagnosis of Lewy body disease with more accurate quantification of nuclear medicine scans.

Ph.D ThesisThis thesis investigates the quantification of two scintigraphic biomarkers used for the diagnosis of dementia with Lewy bodies (DLB): 123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane), commonly known as DaTSCAN™,and cardiac 123I-MIBG(123I-metaiodobenzylguanidine). Accurate quantification is critical as we increasingly move towards diagnosis at the earlier mild cognitive impairment (MCI) stage, where more subtle changes from normality are expected. A range of novel approaches have been examined to overcome technical limitations that have previously been barriers to accurate quantification. Uniquely, this has been studied in cohorts of highly characterised dementia and MCI subjects as well as older adults with normal cognition recruited as age matched controls. The subject studies have been complemented by work using advanced anthropomorphic phantoms. Throughout, the innovative methods have been compared with the established ones. Results are presented in detail and clinical and research relevance is discussed together with proposals for optimal usage. Briefly, the key findings are:FP-CIT key findings•Specific binding ratio values (SBR) for FP-CIT images calculated by different software packages are systematically different, although give similar diagnostic accuracy. •Striatal uptake does not decrease with age in healthy older adults, as previously reported, indicating potential misdiagnosis if age correction is applied. •Absolute quantification separates normal and abnormal subjects less well than relative-quantification with SBR.•Advanced FP-CIT reconstruction methods using SPECT-CT and collimator modelling improve the accuracy of activity concentration measurements in a phantom.•Advanced FP-CIT reconstruction methods affect relative quantification with SBR, but not clinical interpretation. Cardiac MIBG key findings•Different methods of planar MIBG analysis are operator dependent and give systematically different results – recommendations are provided for an optimal method.•Establishing a normal threshold is critical. This thesis shows that previously published values may not be valid in a UK population and proposes a suitable alternative. •Images obtained soon after injection give similar accuracy as those obtained at 3.5 hours (the standard delayed method), and the latter scans could be omitted in the majority of cases. •Planar cardiac MIBG semi-quantification is significantly dependent on subject size. Using SPECT-CT gives greater separation between normal and abnormal scans than planar. II In summary, an in-depth and comprehensive study of technical aspects of Nuclear Medicine biomarker quantification using 123I labelled radiopharmaceuticals for the diagnosis of Lewy body disease is presented in this thesis. This provides a solid foundation for clinical and research application of these techniques in both early and established diseaseAlzheimer’s Societ

Using genetic monitoring to inform best practice in a captive breeding programme:Inbreeding and potential genetic rescue in the freshwater pearl mussel Margaritifera margaritifera

Freshwater pearl mussel (Margaritifera margaritifera) populations are declining in Northern Ireland to the extent that a captive breeding programme was established on the Upper Ballinderry river in 1998. Previous genetic analysis of the hatchery broodstock and their first cohort of offspring showed significant levels of inbreeding (FIS = 0.166). The broodstock, which currently numbers ca. 90 individuals, was supplemented with new individual mussels, whilst in 2013, a previously unknown population was discovered on the Lower Ballinderry river. The aim of the present study was to determine whether the rotation of the broodstock has led to a decrease in the levels of inbreeding in the second cohort of juveniles, and to determine whether the new population found in the Lower Ballinderry was genetically distinct from the captive bred population and populations from the Upper Ballinderry, which represent the source of the hatchery broodstock. Genotyping using eight microsatellite markers indicated that levels of inbreeding in the second cohort of captive-bred mussels were high, (FIS = 0.629), and were comparable to those sampled from the original cohort and the hatchery broodstock (FIS = 0.527 and 0.636 respectively). Bayesian analysis of population structure indicated that the newly discovered Lower Ballinderry population was genetically distinct from the broodstock and its source populations on the Upper Ballinderry. The observed differentiation was primarily due to differences in allele frequencies, and was most likely a result of genetic drift. The occurrence of ten alleles, albeit at low frequency, in the Lower Ballinderry population, including four private alleles, suggests that this new population could be incorporated into the broodstock with the aim of decreasing levels of inbreeding in the future.<br/

Public service interpreters: the emotional and psychological impact of interpreting within public service settings

Professionals working within public services can experience emotional and psychological effects of working with people who are emotionally distressed, such as vicarious trauma and vicarious posttraumatic growth. Public service interpreters play a vital role in helping these professionals communicate effectively with people who are limited in their proficiency of the English language. However, limited research has been conducted into the emotional and psychological impact of public service interpreting in the UK. The aim of this study is to address this gap in the literature through gaining further understanding of the emotional and psychological effects of interpreting within public services using a constructivist grounded theory approach. Ten spoken-language interpreters, recruited through public service interpreting courses in south Wales, engaged in semi-structured interviews about their emotional and psychological experiences while interpreting in public service settings. Five themes were identified, relating to the nature of ‘Public services’; participants’ ‘Relationships with clients’; the ‘Emotional experience’; ‘Psychological changes’ and ‘Coping’. Participants’ experiences were characterised by the short-term experience of distressing emotions, such as anger and sadness, and longer-term psychological changes related to personal growth. The separation of personal and professional boundaries appeared to be a core mediating factor of the emotional and psychological impact of public service interpreting. These findings are discussed in relation to existing literature about the emotional and psychological impact of working with people who are emotionally distressed. The clinical and service delivery implications of this study’s findings include the need for the establishment of formal support systems for public service interpreters and the need for professionals working alongside interpreters to be trained to work with them. Recommendations for future research are also discussed

Contextual influences on the development of resilience for leaders in the workplace

This thesis aims to examine the factors that impact the development of resilience for leaders who take part in resilience interventions in the workplace. Outcomes associated with resilience interventions have been explored in previous research, but despite the increase in resilience intervention delivery for leaders, as yet we know little about how resilience is developed for this specific population. Using a mixed-methods approach, this thesis firstly examines outcomes associated with resilience interventions for leaders, and secondly explores how resilience is developed for this population. Two studies were conducted and are presented in this thesis. The first study was a systematic literature review which examined outcomes associated with leadership interventions where resilience was included as a measure. Five papers met the inclusion and exclusion criteria, and the quality assessment process yielded a low rating. Overall, results indicated there was some evidence for the efficacy of coaching and training interventions supporting the development of resilience for leaders, although it is not clear how specific intervention design components (such as coaching or training) impact resilience, and it is not clear why efficacy is reported for some interventions and not others. Gaps in the research are identified, and are utilised to shape empirical research design, the second study presented in this thesis. The empirical research presented is a four-wave qualitative process evaluation, design to deepen understanding in research gaps including how resilience is developed for leaders taking part in a resilience intervention, and how factors that impact the development of resilience for leaders taking part in an intervention change over time. A total of nine senior leaders from a function within one banking institution completed the study (two dropped out, attrition data is reported), with a 55% male/45% female split, across locations including UK, USA, UAE, China and India. The multi-component intervention delivered comprised of training, coaching and group coaching elements (based on evidence-based design), and qualitative insights were gathered via semi-structured interviews at four time points over five months, pre-, during and post-intervention. Data was analysed using a thematic analysis approach, five higher order themes of individual factors, group factors, leadership factors, organisational factors and outside factors were identified, as well as themes associated with exposure to challenges and specific intervention design elements. A conceptual model of factors that impact both the development of resilience for leaders taking part in an intervention and application of resilience strategies is presented, along with future research recommendations and implications for practitioners, those who commission resilience interventions and intervention participants. This thesis provides novel insights into how resilience is developed for leaders who join resilience interventions in the workplace and has the potential to help shape evidence-based practice for those who design and deliver resilience interventions within organisations

The effects of exposure to images of others’ suffering and vulnerability on altruistic, trust-based, and reciprocated economic decision-making

In this paper we explored the effects of exposure to images of the suffering and vulnerability of others on altruistic, trust-based, and reciprocated incentivized economic decisions, accounting for differences in participants’ dispositional empathy and reported in-group trust for their recipient(s). This was done using a pictorial priming task, framed as a memory test, and a triadic economic game design. Using the largest experimental sample to date to explore this issue, our integrated analysis of two online experiments (total N = 519), found statistically consistent evidence that exposure to images of suffering and vulnerability (vs. neutral images) increased altruistic in-group giving as measured by the “triple dictator game”, and that the manipulation was significantly more effective in those who reported lower trust for their recipients. The experimental manipulation also significantly increased altruistic giving in the standard “dictator game” and trust-based giving in the “investment game”, but only in those who were lower in in-group trust and also high in affective or cognitive empathy. Complementary qualitative evidence revealed the strongest motivations associated with increased giving in the experimental condition were greater assumed reciprocation and a lower aversion to risk. However, no consistent effects of the experimental manipulation on participants’ reciprocated decisions were observed. These findings suggest that, as well as altruistic decision-making in the “triple dictator game”, collaboratively witnessing the suffering of others may heighten trust-based in-group giving in the “investment game” for some people, but the effects are heterogeneous and sensitive to context

Delivery of a Small-For-Gestational-Age Infant and Risk of Maternal Cardiovascular Disease – A Population-Based Record Linkage Study

Background. Delivery of small for gestational age (SGA) infants has been associated with increased risk of future maternal cardiovascular disease (CVD). However, whether the risk increases progressively with the greater severity of SGA and number of SGA infants has not been explored. Methods. A population-based record linkage study was conducted among 812,732 women delivering live born, singleton infants at term between 1994 and 2011 in New South Wales, Australia. Birth records were linked to the mothers’ subsequent hospitalization or death records to identify CVD events (coronary heart disease, cerebrovascular events, and chronic heart failure) after a median of 7.4 years. Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95% confidence interval (CI)] for the associations between the severity (moderate or extreme) of SGA and number of SGA infants and subsequent risk of maternal CVD, accounting for maternal age at last birth, socioeconomic status, parity, smoking, (pre-gestational and gestational) diabetes, and (chronic and pregnancy) hypertension. Results. Compared to mothers of non-SGA infants, AHRs [95%CI] of CVD among mothers of moderately and extremely SGA infants were 1.36 [1.23-1.49], and 1.66 [1.47-1.87], respectively, while AHRs among mothers with 1, 2, and ≥3 SGA infants were 1.42 [1.30-1.54], 1.65 [1.34-2.03], and 2.42 [1.52-3.85], respectively, indicating a dose-response relationship. AHRs of specific CVD categories showed a similar pattern. Conclusions. Delivery of an SGA infant was associated with a dose-dependent increase in the risk of maternal CVD according to both the severity of SGA and number of previous SGA infants.NHMRC, Heart Foundation (Australia

Long term improvements in activities of daily living in patients with hemispatial neglect

No abstract available

Cardiac 123I-MIBG planar heart to mediastinum ratios depend on patient size; phantom studies suggest SPECT-CT could improve quantification.

INTRODUCTION: Planar 123I-MIBG (meta-iodobenzylguanidine) cardiac imaging is listed as an indicative biomarker in the 2017 international consensus criteria for the diagnosis of dementia with Lewy bodies. There has been very little research into the relationship between apparent cardiac uptake and patient size, or in the possible advantage of attenuation and scatter corrected SPECT-CT compared to planar imaging. We aimed to evaluate this in both a chest phantom and in older adults with normal cognition. MATERIALS AND METHODS: An anthropomorphic chest phantom was filled with 123I solution using activities typical of healthy subjects. The phantom was scanned on a Siemens Intevo gamma camera with MELP collimators using both planar and SPECT-CT techniques. Further scans were acquired with a PMMA chest plate added, then water filled plastic breasts. The SPECT-CT images were reconstructed using a resolution recovery OSEM method with and without attenuation and scatter correction (ACSC) applied. Twenty-nine adults over 60 years of age (mean 75.2 ± 8.3 years) underwent planar cardiac MIBG imaging, followed by SPECT-CT. SPECT images were reconstructed as above. Heart-to-mediastinum ratios (HMRs) were calculated for planar and SPECT images. RESULTS: Phantom planar HMR decreased by 20% with the PMMA chest plate added; 39% with plate and breasts. ACSC SPECT cardiac counts showed less dependence on phantom size than SPECT without ACSC (3% versus 37%). The body mass indices (BMI) of the older adults ranged from 22 to 38. There was a significant linear relationship between planar HMR and BMI (R2 = 0.44, p<0.01), but not for ACSC SPECT. However, there was no significant difference between the slopes for planar and ACSC SPECT (p = 0.11). CONCLUSION: Planar cardiac 123I-MIBG HMR results are correlated with BMI. Phantom results suggest that ACSC SPECT can correct for patient size. A large patient population or clinical database would be required to demonstrate a clinical effect