The role of microRNA 21 in the development of in-stent restenosis

Coronary heart disease is a major cause of morbidity and mortality worldwide. Percutaneous coronary intervention (PCI) has become the most widely used method of coronary artery revascularisation. The use of stents to hold open atherosclerosis induced arterial narrowing has significantly reduced elastic recoil and acute vessel occlusion following balloon angioplasty. However, bare metal stents have been associated with in-stent restenosis attributed to vascular smooth muscle cell (VSMC) hyperplasia and excessive neointimal formation. The resultant luminal renarrowing may manifest clinically with the return of symptoms such as chest pain or shortness of breath. The development of drug eluting stents has significantly reduced the incidence of in-stent restenosis (ISR). Unfortunately the antiproliferative medications used not only inhibit VSMC proliferation but also re-endothelialisation of the stented vessel. In addition, the drug impregnated polymer coating has been associated with a chronic inflammatory response within the vessel wall predisposing patients to stent thrombosis. Thus the identification of novel therapies which promote vessel healing without excessive proliferative or inflammatory response may improve long term outcome and reduce the need for repeated revascularisation. MicroRNAs (miRs) are short (18-25 nucleotide) non-coding RNAs acting to regulate gene expression. By binding to the 3’untranslated region of mRNA they act to fine tune gene expression either by mRNA degradation or translational repression. Originally identified in coordinating tissue development microRNAs have also been shown to play important roles coordinating the inflammatory response and in numerous cardiovascular diseases. MiR-21 has been identified in human atherosclerotic plaques, arteriosclerosis obliterans and abdominal aortic aneurysms. In addition, its up regulation has been documented in preclinical models of vascular injury. This study sought to identify the role of miR-21 in the development of ISR. Utilising a small animal model of stenting and in vitro techniques, we sought to investigate its influence upon VSMC and immune cell response following stenting. 19 The refinement of a murine stenting model within the Baker laboratory and the electrochemical dissolution of the metal stent from within harvested vascular tissues significantly improved the ability to perform detailed histological analysis. In addition, identification of miRNAs using in situ hybridisation was achieved for the first time within stented tissue. Neointimal formation and ISR was significantly reduced in mice in which miR-21 had been genetically deleted. In addition, neointimal composition was found to be altered in miR-21 KO mice with reductions in VSMC and elastin content demonstrated. Importantly, no difference in re-endothelialisation was observed. In vitro analysis demonstrated that VSMCs from miR-21 KO mice had both reduced proliferative and migratory capacity following platelet derived growth factor stimulation. Molecular analysis revealed that these differences may, at least in part, be due to de-repression of programmed cell death 4 (PDCD4). PDCD4 is a known miR-21 target within VSMCs implicated in the suppression of proliferation and promotion of apoptosis. Unfortunately, initial attempts at antimiR mediated knockdown of miR-21 in vivo, failed to produce a similar change in the suppression of ISR. Furthermore, a significant alteration in macrophage polarisation state within the neointima of miR-21 WT and KO mice was noted. Immunohistochemical staining revealed a preponderance of anti-inflammatory M2 macrophages in KO mice. Analysis of bone marrow derived macrophages from miR-21 KO mice demonstrated an increased level of the peroxisome proliferation activating receptor-γ (PPARγ) which facilitates M2 polarisation. Importantly, significant alterations in numerous pro-inflammatory cytokines, which also have mitogenic effects, were also found following genetic deletion of miR-21. In Summary, this is the first study to look at miRs in the development of ISR. MiR-21 plays an important role in the development of ISR by influencing the proliferative response of VSMCs and modulating the immune response following stent deployment. Further attempts to modulate miR-21 expression following PCI may reduce ISR and the need for repeat revascularisation while also reducing the risk of stent thrombosis.

The Productive use of Failure to Generate Witnesses from Divergent Proof Attempts for Coinduction

Coinduction is a proof rule. It is the dual of induction. It allows reasoning about non--well--founded structures such as lazy lists or streams and is of particular use for reasoning about equivalences. A central difficulty in the automation of coinductive proof is the choice of a relation (called a bisimulation). We present an automation of coinductive theorem proving. This automation is based on the idea of proof planning. Proof planning constructs the higher level steps in a proof, using knowledge of the general structure of a family of proofs and exploiting this knowledge to control the proof search. Part of proof planning involves the use of failure information to modify the plan by the use of a proof critic which exploits the information gained from the failed proof attempt. Our approach to the problem was to develop a strategy that makes an initial simple guess at a bisimulation and then uses generalisation techniques, motivated by a critic, to refine this guess, so that a larger class of coinductive problems can be automatically verified. The implementation of this strategy has focused on the use of coinduction to prove the equivalence of programs in a small lazy functional language which is similar to Haskell. We have developed a proof plan for coinduction and a critic associated with this proof plan. These have been implemented in CoClam, an extended version of Clam with encouraging results. The planner has been successfully tested on a number of theorems.

Lantana: current management status and future prospects.

Lantana camara L. is a significant weed of which there are some 650 varieties in over 60 countries or island groups. It has been the focus of biological control attempts for a century, yet still poses major problems in many regions. Lantana has a significant impact on economic and environmental areas and is difficult to control. The key to good management of lantana is constant vigilance. Repeated control of new regrowth is critical to success. Control of new infestations should be a priority because the species is able to expand its range during good seasons, but does not die out during poor conditions. This book is a resource for land managers and researchers on methods of lantana control, particularly biocontrol.

Clydebank in the inter-war years: a study in economic and social change

The main theme of this thesis is the social, economic and political response of a single community to economic dislocation in the interwar years. The community under consideration is Clydebank., The thesis is divided into several parts. Part I establishes the development of the burgh and considers the physical framework of the community, mainly in the years before 1919. The town's characteristics are examined in terms of population structure and development between the world wars. In the last part of this section there is a review of the economic structure of the burgh and changes occurring in it between 1919 and 1939. In Part II consideration is given to the actual extent and form of the unemployment affecting Clydebank at this time, and comparison is made with other communities and geographic/economic areas. Attention is then focussed more narrowly on the actual individuals suffering unemployment in the burgh during the 1930s, in an attempt to personalise the experience of the unemployed. Part III reviews central and local government responses to the situation in which Clydebank found itself oetween 1919 and 1939. Central government policies discussed include unemployment insurance, public works, the Special Areas legislation, assistance in the construction of the 534 "Queen Mary" and the direction of financial support to areas of particular need. Amongst local authority actions described are additional local support for the poor, public works, efforts to attract new industry to the town, attempts to deal with the housing problem which was particularly acute at times of high unemployment and measures to maintain health standards in the community. In Part IV the responses of the community to unemployment and government policies are detailed. The burgh's commercial sector is surveyed as are developments in leisure provision, religion, temperance and crime, and local politics. A number of individual responses are also given consideration such as migration, commuting, changes in birth and marriage rates and suicide.

Exploring the Process of Meaning-making after Partner Suicide

Meaning-making is increasingly recognized as a fundamental aspect of the grief experience. This study investigated the process of meaning-making in the narratives of individuals whose partners died by suicide, exploring their meaning reconstruction in response to this form of loss. The narratives of users of a public online grief support forum (n = 50) were analyzed using the Meaning of Loss Codebook (Gillies, Neimeyer, & Milman, 2014), which consists of core categories of meaning of loss in response to the death of a loved one. The results indicated that these individuals predominantly experienced negative affect, a lack of understanding associated with the loss, and a longing for their partners. The grief experience of participants in this study was marked by substantial psychological distress and an ongoing struggle to make sense of and find meaning in this type of loss. It is clear that grieving the loss of a partner as a result of suicide presents unique challenges to meaning-making in comparison to other types of loss. Given the importance of this aspect of adjustment to loss, these findings deepen the understanding of this component of grief and inform the provision of support for those grieving a loved one who died by suicide.

Long term repeated fire disturbance alters soil bacterial diversity but not the abundance in an Australian wet sclerophyll forest

Effects of fire on biogeochemical cycling in terrestrial ecosystem are widely acknowledged, while few studies have focused on the bacterial community under the disturbance of long-term frequent prescribed fire. In this study, three treatments (burning every two years (B2), burning every four years (B4) and no burning (B0)) were applied for 38 years in an Australian wet sclerophyll forest. Results showed that bacterial alpha diversity (i.e. bacterial OTU) in the top soil (0-10 cm) was significantly higher in the B2 treatment compared with the B0 and B4 treatments. Non-metric multidimensional analysis (NMDS) of bacterial community showed clear separation of the soil bacterial community structure among different fire frequency regimes and between the depths. Different frequency fire did not have a substantial effect on bacterial composition at phylum level or bacterial 16S rRNA gene abundance. Soil pH and C:N ratio were the major drivers for bacterial community structure in the most frequent fire treatment (B2), while other factors (EC, DOC, DON, MBC, NH 4 +, TC and TN) were significant in the less frequent burning and no burning treatments (B4 and B0). This study suggested that burning had a dramatic impact on bacterial diversity but not abundance with more frequent fire.

Efeitos de mudanças sucessivas na definição de produto agregado em metacontingências

Dissertação (mestrado)—Universidade de Brasília, Instituto de Psicologia, Departamento de Processos Psicológicos Básicos, Programa de Pós-Graduação em Ciências do Comportamento, 2015.

Starotestamentalny kontekst opisów cudownych uwolnień z Dziejów Apostolskich

Wydział Teologiczny

Smoking, depression, and suicide risk in the nursing staff of a Third-Level Hospital

Objective: To determine the association between smoking, depression and suicide risk in the Nursing Staff of a University Hospital. Materials and method: this was a non-experimental, correlational cross-range study with observational analysis carried out between May 2012 and May 2013. We studied 232 nurses of the “Dr. José Eleuterio gonzález” University Hospital. two self-administered scales were applied, one for depression and one for suicide risk. Another hetero-applied scale of nicotine dependency was also used, and the subjects’ socio-demographic records were reviewed. Results: A total of 527,232 nurses were studied. A smoking prevalence of 22.8% (53 subjects), an operational depression prevalence of 15.1% (35 subjects), and a suicide risk of 5.1% (12 subjects) were found. Gender and age, speciically being male and young (mean age 29.2 years) were found to increase the risk of smoking. We also found that those nurses who had a partner and had a higher level of education smoked less compared to those who did not have a partner or had a lower degree of education. there were hospital departments where there was a higher prevalence of smoking, such as Internal Medicine and Shock trauma. No association between smoking and the presence of depression was found. Regarding depression, we found that those nurses who worked in the Department of Pensioners were more likely to develop operational depression than those working in any other department. We also found that the risk of presenting operational depression decreases as age increases. About suicide risk, a statistically signiicant association between smoking and suicide risk was found. We also found an association between operational depression and suicide risk.Conclusions: It is recommended to consider nicotine dependence as a fundamental part of psychopathology assessment because of its strong association with suicide risk. this study emphasizes the complexity of the issue of the comorbidity of smoking and psychopathology and the need to continue research lines.

Repeated Reading Strategy for Students with Intellectual Disabilities

Repeated Reading Strategy used with Intellectually Disabled Students in order to increase reading fluency and comprehension.

Repeated Readings to Promote Fluency for Students with Intellectual Disabilities

Reading fluency is a skill that’s difficult for many students to acquire. However, research suggests that consistently implementing the Repeated Reading intervention can help students increase fluency and comprehension. The effect of this strategy when used to promote reading fluency in secondary students with severe intellectual disabilities has yet to be investigated. My research will examine the effect of the Repeated Reading intervention on the fluency level of students with intellectual disabilities in a public high school.

Change, stability and prediction of gross motor co-ordination in portuguese children

The knowledge about intra- and inter-individual variation can stimulate attempts at description, interpretation and prediction of motor co-ordination (MC). Aim: To analyse change, stability and prediction of motor co-ordination (MC) in children. Subjects and methods: A total of 158 children, 83 boys and 75 girls, aged 6, 7 and 8 years, were evaluated in 2006 and re-evaluated in 2012 at 12, 13 and 14 years of age. MC was assessed through the Kiphard-Schilling’s body co-ordination test and growth, skeletal maturity, physical fitness, fundamental motor skills (FMS), physical activity and socioeconomic status (SES) were measured and/or estimated. Results: Repeated-measures MANOVA indicated that there was a significant effect of group, sex and time on a linear combination of the MC tests. Univariate tests revealed that group 3 (8–14 years) scored significantly better than group 1 (6–12 years) in all MC tests and boys performed better than girls in hopping for height and moving sideways. Scores in MC were also higher at follow-up than at baseline. Inter-age correlations for MC were between 0.15–0.74. Childhood predictors of MC were growth, physical fitness, FMS, physical activity and SES. Biological maturation did not contribute to prediction of MC. Conclusion: MC seemed moderately stable from childhood through adolescence and, additionally, inter-individual predictors at adolescence were growth, FMS, physical fitness, physical activity and SES.

Effectiveness of Depression-Suicidal Behaviour Gatekeeper training among police officers in three European regions: outcomes of the Optimising Suicide Prevention Programmes and their Implementation in Europe (OSPI-Europe) study

Background: Gatekeeper training for community facilitators, to identify and respond to those at risk of suicide, forms an important part of multi-level community-based suicide prevention programmes. Aims: This study examined the effects of gatekeeper training on attitudes, knowledge and confidence of police officers in dealing with persons at risk of suicide. Methods: A total of 828 police officers across three European regions participated in a 4-hour training programme which addressed the epidemiology of depression and suicidal behaviour, symptoms of depression, warning signs and risk factors associated with suicidal behaviour, motivating help-seeking behaviour, dealing with acute suicidal crisis and informing bereaved relatives. Participants completed internationally validated questionnaires assessing stigmatising attitudes, knowledge about depression and confidence in dealing with suicidal persons pre- and post-training. Results: There were significant differences among countries in terms of previous exposure to suicidal persons and extent of previous training. Post-training evaluation demonstrated significant improvements in stigmatising attitudes, knowledge and confidence in all three countries. Conclusion: The consistently positive effects of gatekeeper training of police officers across different regions support inclusion of this type of training as a fundamental part of multi-level community-based suicide prevention programmes and roll-out, nationally and internationally.

Suicide among young people and adults in Ireland: method characteristics, toxicological analysis and substance abuse histories compared

Objective: Information on factors associated with suicide among young individuals in Ireland is limited. The aim of this study was to identify socio-demographic characteristics and circumstances of death associated with age among individuals who died by suicide. Methods: The study examined 121 consecutive suicides (2007–2012) occurring in the southern eastern part of Ireland (Cork city and county). Data were obtained from coroners, family informants, and health care professionals. A comparison was made between 15-24-year-old and 25-34-year-old individuals. Socio-demographic characteristics of the deceased, methods of suicide, history of alcohol and drug abuse, and findings from toxicological analysis of blood and urine samples taken at post mortem were included. Pearson’s χ2 tests and binary logistic regression analysis were performed. Results: Alcohol and/or drugs were detected through toxicological analysis for the majority of the total sample (79.5%), which did not differentiate between 15-24-year-old and 25-34-year-old individuals (74.1% and 86.2% respectively). Compared to 25-34-year-old individuals, 15-24-year-old individuals were more likely to engage in suicide by hanging (88.5%). Younger individuals were less likely to die by intentional drug overdose and carbon monoxide poisoning compared to older individuals. Younger individuals who died between Saturday and Monday were more likely to have had alcohol before dying. Substance abuse histories were similar in the two age groups. Conclusion: Based on this research it is recommended that strategies to reduce substance abuse be applied among 25-34-year-old individuals at risk of suicide. The wide use of hanging in young people should be taken into consideration for future means restriction strategies.