Social vulnerability in Williams syndrome

This thesis focused on the high levels of social vulnerability experienced by individuals with Williams Syndrome (WS). The investigation began with parent interviews about social approach behaviour, with parents emphasising the lack of awareness of social boundaries that many individuals with WS display. The qualitative analysis also highlighted the within-syndrome variability in the parental accounts, prompting discussion on the heterogeneity of the WS social profile. Based on the atypical social approach behaviour described by parents, the subsequent studies addressed issues of personal space and interpersonal distance. Using a parent report questionnaire, it was found that children with WS were more likely to violate the personal space of others. This was followed up with a stop-distance paradigm which showed that children with WS failed to regulate their distance based on familiarity, and stood the same distance from a stranger as they did their parent, which was not the case for typically developing individuals. Given these findings, the research progressed to explore the issue of trust in WS. It was found that children with WS displayed higher levels of trust behaviour, compared to their mental age matched typically developing peers and struggled to decipher trustworthiness from faces. Taken together, these findings seem to suggest that children with WS could be experiencing high levels of social vulnerability on a daily basis. It is widely accepted that this social vulnerability continues into adulthood, with increased levels of both independence and isolation posing a new set of challenges. The subsequent chapter probed the level of insight that adults with WS had about their own vulnerability. Using the Social Vulnerability Questionnaire, it was found that adults with WS consistently reported lower levels of vulnerability, compared to parent reports. This emphasised the need for multi-informant methods, and called for interventions which target self-awareness in order to increase intervention efficacy. The final chapters looked at how this social vulnerability manifests in the online environment. It was found that adults with WS frequently use the Internet and the majority visit social networking sites every day or almost every day, with little parental supervision or oversight. These individuals were more likely to agree to engage in socially risky behaviours (e.g. meeting an “online friend” in person) compared to risky behaviours that were not social in nature when online (e.g. giving out passwords). A case study interview with an adult with WS and their parent highlighted that this individual held a broad definition of what a friend was and found they used the Internet as a tool to expand their social network, which was of great concern to their parent. The findings included in this thesis provide in-depth information relating to social vulnerability in WS and offer the first insights into online social behaviour and online vulnerability in adults with WS. The theoretical and real-world implications of these findings are emphasised throughout and a number of suggestions are made to help the research progress towards intervention development

The influence of associated reactions on upper limb performance following stroke

The recovery of movement following a stroke is often affected by increased reflex activity. Associated reactions are one manifestation of this activity. In early studies it is reported that associated reactions, elicited by semi-reflex activity or voluntary movement elsewhere, result in increased muscle tone and movement in the static, hemiparetic upper limb. In the physiotherapeutic treatment of stroke, importance is attached to the influence of reflex behaviour on the control of movement. [Continues.

Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis

Background: Coccidiosis is a major contributor to losses in poultry production. With emerging constraints on the use of in-feed prophylactic anticoccidial drugs and the relatively high costs of effective vaccines, there are commercial incentives to breed chickens with greater resistance to this important production disease. To identify phenotypic biomarkers that are associated with the production impacts of coccidiosis, and to assess their covariance and heritability, 942 Cobb500 commercial broilers were subjected to a defined challenge with Eimeria tenella (Houghton). Three traits were measured: weight gain (WG) during the period of infection, caecal lesion score (CLS) post mortem, and the level of a serum biomarker of intestinal inflammation, i.e. circulating interleukin 10 (IL-10), measured at the height of the infection.Results: Phenotypic analysis of the challenged chicken cohort revealed a significant positive correlation between CLS and IL-10, with significant negative correlations of both these traits with WG. Eigenanalysis of phenotypic covariances between measured traits revealed three distinct eigenvectors. Trait weightings of the first eigenvector, (EV1, eigenvalue = 59%), were biologically interpreted as representing a response of birds that were susceptible to infection, with low WG, high CLS and high IL-10. Similarly, the second eigenvector represented infection resilience/resistance (EV2, 22%; high WG, low CLS and high IL-10), and the third eigenvector tolerance (EV3, 19%; high WG, high CLS and low IL-10), respectively. Genome-wide association studies (GWAS) identified two SNPs that were associated with WG at the suggestive level.Conclusions: Eigenanalysis separated the phenotypic impact of a defined challenge with E. tenella on WG, caecal inflammation/pathology, and production of IL-10 into three major eigenvectors, indicating that the susceptibility-resistance axis is not a single continuous quantitative trait. The SNPs identified by the GWAS for body weight were located in close proximity to two genes that are involved in innate immunity (FAM96B and RRAD)

Exercise-based rehabilitation for heart failure : systematic review and meta-analysis

Objective: To update the Cochrane systematic review of exercise-based cardiac rehabilitation (CR) for heart failure. Methods: A systematic review and meta-analysis of randomised controlled trials was undertaken. MEDLINE, EMBASE and the Cochrane Library were searched up to January 2013. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise interventions alone or as a component of comprehensive CR programme compared with no exercise control. Results: 33 trials were included with 4740 participants predominantly with a reduced ejection fraction (<40%) and New York Heart Association class II and III. Compared with controls, while there was no difference in pooled all-cause mortality between exercise CR with follow-up to 1 year (risk ratio (RR) 0.93; 95% CI 0.69 to 1.27, p=0.67), there was a trend towards a reduction in trials with follow-up beyond 1 year (RR 0.88; 0.75 to 1.02, 0.09). Exercise CR reduced the risk of overall (RR 0.75; 0.62 to 0.92, 0.005) and heart failure-specific hospitalisation (RR 0.61; 0.46 to 0.80, 0.0004) and resulted in a clinically important improvement in the Minnesota Living with Heart Failure questionnaire (mean difference: −5.8 points, −9.2 to −2.4, 0.0007). Univariate meta-regression analysis showed that these benefits were independent of the type and dose of exercise CR, and trial duration of follow- up, quality or publication date. Conclusions: This updated Cochrane review shows that improvements in hospitalisation and health-related quality of life with exercise-based CR appear to be consistent across patients regardless of CR programme characteristics and may reduce mortality in the longer term. An individual participant data meta-analysis is needed to provide confirmatory evidence of the importance of patient subgroup and programme level characteristics (eg, exercise dose) on outcome

Exercise based rehabilitation for heart failure (Review)

Background: From previous systematic reviews and meta-analyses there is consensus about the positive effect of exercise training on exercise capacity; however, the effects on health-related quality of life, mortality and hospital admissions in heart failure remain uncertain. Objectives: To update the previous systematic review which determined the effectiveness of exercise-based interventions on the mortality, hospitalisation admissions, morbidity and health-related quality of life for patients with systolic heart failure. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4). To update searches from the previous review, MEDLINE, EMBASE, CINAHL, and PsycINFO were searched (2001 to January 2008). ISI Proceedings and bibliographies of identified reviews were checked. Selection criteria: Randomised controlled trials of exercise-based interventions with six months follow up or longer compared to usual medical care or placebo. The study population comprised adults of all ages (> 18 years) with evidence of chronic systolic heart failure. Data collection and analysis: All identified references were independently screened by two review authors and those that were clearly ineligible were rejected. Full papers of potentially relevant trials were obtained. Data were independantly extracted from the included trials and their risk of bias assessed by a single review author and checked by a second. Main results: Nineteen trials (3647 participants) met the inclusion criteria. One large trial recuited 2331 of the participants. There was no significant difference in pooled mortality between groups in the 13 trials with 1 year follow up. A reduction in the hospitalisation rate was demonstrated with exercise training programmes. Hospitalisations due to systolic heart failure were reduced with exercise and there was a significant improvement in health-related quality of life (HRQoL). The effect of cardiac exercise training on total mortality and HRQoL were independent of the degree of left ventricular dysfunction, type of cardiac rehabilitation, dose of exercise intervention, length of follow up, trial quality, and trial publication date. Authors' conclusions: The previous version of this review showed that exercise training improved exercise capacity in the short term in patients with mild to moderate heart failure when compared to usual care. This updated review provides evidence that in a similar population of patients, exercise does not increase the risk of all-cause mortality and may reduce heart failure-related hospital admissions. Exercise training may offer important improvements in patients' health-related quality of life

Exercise-based rehabilitation for heart failure

Background Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010. Objectives To determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF'). Search methods We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov). Selection criteria Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF. Data collection and analysis Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data. Main results We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved. Authors' conclusions This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting

Feasibility and Impact of a Combined Supervised Exercise and Nutritional-Behavioral Intervention following Bariatric Surgery: A Pilot Study

Background. Lifestyle intervention programs after bariatric surgery have been suggested to maximise health outcomes. This pilot study aimed to investigate the feasibility and impact of an 8-week combined supervised exercise with nutritional-behavioral intervention following Roux-en-Y gastric bypass and sleeve gastrectomy. Methods. Eight female patients (44 ± 8 years old, BMI = 38.5 ± 7.2 kgm−2) completed the program. Before and after intervention, anthropometric measures, six-minute walk test (6MWT), physical activity level, eating behavior, and quality of life (QoL) were assessed. Percentage weight loss (%WL) outcomes were compared with a historical matched control group. Results. The program significantly improved functional capacity (mean increment in 6MWT was 127 ± 107 meters, p=0.043), increased strenuous intensity exercise (44 ± 49 min/week, p=0.043), increased consumption of fruits and vegetables (p=0.034), reduced consumption of ready meals (p=0.034), and improved “Change in Health” in QoL domain (p=0.039). The intervention group exhibited greater %WL in the 3–12-month postsurgery period compared to historical controls, 12.2 ± 7.5% versus 5.1 ± 5.4%, respectively (p=0.027). Conclusions. Lifestyle intervention program following bariatric surgery is feasible and resulted in several beneficial outcomes. A large randomised control trial is now warranted

Potential effects of climate change on Australian estuaries and fish utilising estuaries: a review

Estuaries are especially vulnerable to the impacts of climate change because changes in climatic and hydrologic variables that influence freshwater and marine systems will also affect estuaries. We review potential impacts of climate change on Australian estuaries and their fish. Geographic differences are likely because southern Australian climates are predicted to become warmer and drier, whereas northern regions may see increased precipitation. Environmental factors, including salinity gradients, suspended sediment, dissolved oxygen and nutrient concentrations, will be influenced by changing freshwater input and other climate variables. Potential impacts will vary depending on the geomorphology of the estuary and the level of build-up of sand bars across estuarine entrances. Changes to estuarine fish assemblages will depend on associated changes to salinity and estuarine-mouth morphology. Marine migrants may be severely affected by closure of estuarine mouths, depending on whether species 'must' use estuarine habitat and the level of migratory v. resident individuals. Depending on how fish in coastal waters locate estuaries, there may be reduced cues associated with estuarine mouths, particularly in southern Australia, potentially influencing abundance. In summary, climate change is expected to have major consequences for Australian estuaries and associated fish, although the nature of impacts will show significant regional variation

Exercise training for systolic heart failure: Cochrane systematic review and meta-analysis

AIMS: To determine the effect of exercise training on clinical events and health-related quality of life (HRQoL) of patients with systolic heart failure. METHODS AND RESULTS: We searched electronic databases including Medline, EMBASE, and Cochrane Library up to January 2008 to identify randomized controlled trials (RCTs) comparing exercise training and usual care with a minimum follow-up of 6 months. Nineteen RCTs were included with a total of 3647 patients, the majority of whom were male, low-to-medium risk, and New York Heart Association class II-III with a left ventricular ejection fraction of <40%. There was no significant difference between exercise and control in short-term (<or=12 months) or longer-term all-cause mortality or overall hospital admissions. Heart failure-related hospitalizations were lower [relative risk: 0.72, 95% confidence interval (CI): 0.52-0.99] and HRQoL improved (standardized mean difference: -0.63, 95% CI: -0.80 to -0.37) with exercise therapy. Any effect of cardiac exercise training on total mortality and HRQoL was independent of degree of left ventricular dysfunction, type of cardiac rehabilitation, dose of exercise intervention, length of follow-up, trial quality, and trial publication date. CONCLUSION: Compared with usual care, in selected heart failure patients, exercise training reduces heart failure-related hospitalizations and results in clinically important improvements in HRQoL. High-quality RCT and cost-effectiveness evidence is needed for the effect of exercise training in community-based settings and in more severe heart failure patients, elderly people, and women

Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an&nbsp;important model system to study epithelial stem cell populations and how they respond to tissue stresses