Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

Reliability of the Five Factor Wellness Inventory among male adolescents

Measuring adolescent wellness can assist researchers and practitioners in determining lifestyle behaviors in which adolescents are deficient. An appropriate objective assessment may assist male adolescents who feel uncomfortable revealing behaviors that may indicate wellness deficits. The authors examined the test-retest reliability of the Five Factor Wellness Inventory (5F-Wel) with a sample of male adolescents. Thirty-five participants self-completed the 5F-Wel on two separate occasions, 7 days apart. Limits of agreement, intraclass correlation coefficients, and paired t tests were calculated to investigate agreement and whether systematic differences existed between administrations. The initial findings indicate the 5F-Wel is reliable for use among male adolescents and support its use in research.

Interacting constraints shape emergent decision-making of referees

How and why football referees made decisions was investigated. A constructivist grounded theory methodology was undertaken to tap into the experiential knowledge of referees. The participant cohort comprised 7 A-League referees (aged 23 to 35) and 8 local Brisbane league referees (aged 20 to 50), spanning the lowest to highest levels of competition in men’s football in Australia. Results found that referees used ‘four pillars’ to underpin their judgments, these were conceptual notions of: safety, fairness, accuracy and entertainment. A fifth pillar ‘consistency’ referred to the referee’s ‘contextual sensitivity’. Results were explained using an ecological dynamics framework that emphasises the individual-environment scale of analysis. It was concluded that interacting constraints shape emergent decision-making in referees which are nested in task goals.

The role for police in addressing alcohol-related harm inside and outside licensed premises

Alcohol consumption is enmeshed with Australian culture (Palk, 2008) and the use and misuse of alcohol contributes to considerable health and social harms (Barbor et al., 2010; English et al., 1995; Gutjahr, Gmel, & Rehm, 2001; Palk, 2008; Steenkamp, Harrison, & Allsop, 2002). Despite shifts in the way that alcohol is consumed and how it is used, it has been reported that one-third of all alcohol consumed is done so within licensed premises (Lang, Stockwell, Rydon, & Gamble, 1992). Consequently, licensed premises are over-represented as settings in which alcohol-related harms occur. These harms, particularly those related to violence, are associated with particular licensed premises operating in the night-time economy (Briscoe & Donnelly, 2001b; Chikritzhs, Stockwell, & Masters, 1997; Homel, Tomsen, & Thommeny, 1991; Stockwell, 1997). Police have a role in not only responding to the manifestation of harms, such as crime, injuries, assaults, domestic violence, stealing and sexual offences, but they also have a role in preventing problems, and thereby reducing alcohol and other drug-related harms (Doherty & Roche, 2003). Given the extent of alcohol consumption within licensed premises and the nature and extent of the harms, as well as the lack of opportunity to influence outcomes in other settings (e.g. the home), licensed premises offer police and other stakeholders a significant opportunity to influence positively the reduction of alcoholrelated harm. This research focuses specifically on the police role in policing licensed premises. Primarily, this research aims to investigate the factors which are relevant to why and how police officers respond to alcohol-related incidents inside and outside licensed premises. It examines the attitudes and beliefs of police and assesses their knowledge, capacity and ability to effectively police licensed premises. The research methodology uses three distinct surveys. Each contributes to understanding the motivations and practice of police officers in this important area of harm reduction. Study One involved a survey of police officers within a police district (Brisbane Central District) in Queensland, Australia and used a comprehensive questionnaire involving both quantitative and qualitative techniques. A key research outcome of Study One was the finding that officers had low levels of knowledge of the strategies that are effective in addressing alcohol-related harm both inside and outside licensed premises. Paradoxically, these officers also reported extensive recent experience in dealing with alcohol issues in these locations. In addition, these officers reported that alcohol was a significant contextual factor in the majority of matters to which they responded. Officers surveyed reported that alcohol increased the difficulty of responding to situations and that licensed premises (e.g. nightclubs, licensed clubs and hotels) were the most difficult contexts to police. Those surveyed were asked to self-assess their knowledge of the Liquor Act (Qld), which is the primary legislative authority in Queensland for regulating licensed premises. Surprisingly, well over half of the officers (65%) reported ‘no’ to ‘fair’ knowledge of the Act, despite officers believing that their skill level to police such premises was in the ‘good to very good range’. In an important finding, officers reported greater skill level to police outside licensed premises than inside such premises, indicating that officers felt less capable, from a skill perspective, to operate within the confines of a licensed premise than in the environment immediately outside such premises. Another key finding was that officers reported greater levels of training in responding to situations outside and around licensed premises than to situations inside licensed premises. Officers were also asked to identify the frequency with which they employed specified regulatory enforcement and community-based strategies. Irrespective of the type of response, ‘taking no action’ or passive policing interventions were not favoured by officers. The findings identified that officers favoured taking a range of strategies (sending home, releasing into the custody of friends, etc.) in preference to arrest. In another key finding, officers generally reported their support for operational stakeholder partnership approaches to policing licensed premises. This was evidenced by the high number of officers (over 90%) reporting that there should be shared responsibility for enforcing the provisions of the Liquor Act. Importantly, those surveyed also identified the factors which constrain or prevent them from policing licensed premises. Study Two involved interviewing a small but comprehensive group (n=11) of senior managers from within the Queensland Police Service (QPS) who have responsibility for setting operational and strategic policy. The aim of this study was to examine the attitudes, perceptions and influence that senior officers (at the strategy and policy-setting level) had on the officers at the operational level. This qualitative study was carried out using a purposive sampling (Denzin & Lincoln, 2005; Guba & Lincoln, 1989), focused interview and thematic analytic approach. The interview participants were drawn from three tiers of management at district, regional as well as the whole-of-organisational level. The first key theme emerging from the study related to role, in terms of both the QPS broader organisational role, and the individual officer role with respect to the policing of licensed premises. For the QPS organisational role, participants at all three strategic levels had a high degree of congruity as to the organisations service role; that is, to enhance public safety. With respect to participants’ beliefs as to whether police officers have knowledge and understanding of their individual roles concerning licensed premises (as opposed to the QPS role), participants reported most commonly that officers had a reasonable to clear understanding of their role. Participant comments also were supportive of the view that officers operating in the research area, Brisbane Central District (BCD), had a clearer understanding of their role than police operating in other locations. The second key theme to emerge identified a disparity between the knowledge and capability of specialist police, compared with general duties police, to police licensed premises. In fact, a number of the responses to a variety of questions differentiated specialist and general police in a range of domains. One such example related to the clarity of understanding of officer role. Participants agreed that specialist police (Liquor Enforcement & Proactive Strategies [LEAPS] officers) had more clarity of understanding in terms of their role than generalist police. Participants also were strongly of the opinion that specialist police had higher skill levels to deal with issues both inside and outside licensed premises. Some participants expressed the view that general duty police undertook purely response-related activities, or alternatively, dealt with lower order matters. Conversely, it was viewed that specialist police undertook more complex tasks because of their higher levels of knowledge and skill. The third key theme to emerge concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Participant responses strongly indicated that there was a diversity of resourcing barriers that restrict police from undertaking their roles in licensed premises. Examples of such barriers were the lack of police and the low ratio of police to patrons, available officer time, and lack of organisational investment in skills and knowledge acquisition. However, some participants indicated that police resourcing in the BCD was appropriate and officers were equipped with sufficient powers (policy and legislation). Again, the issue of specialist police was raised by one participant who argued that increasing the numbers of specialist police would ameliorate the difficulties for police officers policing licensed premises. The fourth and last key theme to emerge from Study Two related to the perception of senior officers regarding the opportunity and capability of officers to leverage off external partnerships to reduce harms inside and outside licensed premises. Police working in partnership in BCD was seen as an effective harm reduction strategy and strongly supported by the participants. All participants demonstrated a high degree of knowledge as to who these partners were and could identify those government, non-government and community groups precisely. Furthermore, the majority of participants also held strong views that the partnerships were reasonably effective and worked to varying degrees depending on the nature of the partnership and issues such as resourcing. These senior officers identified better communication and coordination as factors that could potentially strengthen these partnerships. This research finding is particularly important for senior officers who have the capacity to shape the policy and strategic direction of the police service, not only in Queensland but throughout Australasia. Study Three examined the perceptions of those with links to the broader liquor industry (government, non-government and community but exclusive of police) concerning their understanding of the police role and the capacity of police to reduce alcohol-related harm inside and outside licensed premises, and their attitudes towards police. Participants (n=26) surveyed represented a range of areas including the liquor industry, business represenatives and government representatives from Queensland Fire and Rescue Service, Queensland Ambulance Service, Brisbane City Council and Queensland Health. The first key theme to emerge from Study Three related to participant understanding of the QPS organisational role, and importantly, individual officer role in policing licensed premises. In terms of participant understanding of the QPS role there was a clear understanding by the majority of participants that the police role was to act in ways consistent with the law and to otherwise engage in a range of enforcement-related activities. Participants saw such activities falling into two categories. The first category related to reactive policing, which included actions around responding to trouble in licensed premises, monitoring crowd controllers and removing trouble-makers. In the second category, proactive approaches, participants identified the following activities as consistent with that approach: early intervention with offenders, support of licensed premises operators and high visibility policing. When participants were asked about their understanding of individual officer roles in the policing of licensed premises, a range of responses were received but the consistent message that emerged was that there is a different role to be played by general duty (uniformed) police compared to specialist (LEAPS Unit) police, which reflects differences in knowledge, skill and capability. The second key theme that emerged from the data related to the external participants’ views of the knowledge and capability of specialist police, compared with general duty police, to police licensed premises. As noted in the first key theme, participants were universally of the view that the knowledge, skill and capability of police in specialist units (LEAPS Unit) was at a higher level than that of general duty police. Participants observed that these specialist officers were better trained than their colleagues in generalist areas and were therefore better able to intervene knowledgeably and authoritatively to deal with problems and issues as they emerged. Participants also reported that officers working within BCD generally had a positive attitude to their duties and had important local knowledge that they could use in the resolution of alcohol-related issues. Participants also commented on the importance of sound and effective QPS leadership, as well as the quality of the leadership in BCD. On both these measures, there was general consensus from participants, who reported positively on the importance and effectiveness of such leadership in BCD. The third key theme to emerge from Study Three concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Overwhelmingly, external participants reported the lack of human resources (i.e. police officers) as the key barrier. Other resourcing limitations, such as available officer time, police computer systems, and the time taken to charge offenders, were identified as barriers. Some participants identified barriers in the liquor industry such as ‘dodgy operators’ and negative media attention as limitations. Other constraints to emerge related to government and policy barriers. These were reflected in comments about the collection by government of fees from licensees and better ‘powers’ for police to deal with offenders. The fourth and final key theme that emerged from Study Three related to the opportunities for and capability of police to leverage off external partnerships to reduce harms inside and outside licensed premises. Not surprisingly, participants had a comprehensive knowledge of a broad range of stakeholders, from a diversity of contexts, influential in addressing issues in licensed premises. Many participants reported their relationships with the police and other stakeholders as effective, productive and consistent with the objectives of partnering to reduce alcohol-related harm. On the other hand, there were those who were concerned with their relationship with other stakeholders, particularly those with a compliance function (e.g. Office of Liquor & Gaming Regulation [OLGR]). The resourcing limitations of partners and stakeholders were also raised as an important constraining factor in fulfilling the optimum relationship. Again, political issues were mentioned in terms of the impact on partnerships, with participants stating that there is at times political interference and that politicians complicate the relationships of stakeholders. There are some significant strengths with respect to the methodology of this research. The research is distinguished from previous work in that it examines these critical issues from three distinct perspectives (i.e. police officer, senior manager and external stakeholder). Other strengths relate to the strong theoretical framework that guides and informs the research. There are also some identified limitations, including the subjective nature of self-report data as well as the potential for bias by the author, which was controlled for using a range of initiatives. A further limitation concerns the potential for transferability and generalisability of the findings to other locations given the distinctive nature of the BCD. These limitations and issues of transferability are dealt with at length in the thesis. Despite a growing body of literature about contextual harms associated with alcohol, and specific research concerning police intervention in such contextual harms, there is still much to learn. While research on the subject of police engaging in alcohol-related incidents has focused on police behaviours and strategies in response to such issues, there is a paucity of research that focuses on the knowledge and understanding of officers engaged in such behaviours and practices. Given the scarcity of research dealing with the knowledge, skills and attitudes of police officers responding to harms inside and outside licensed premises, this research contributes significantly to what is a recent and growing body of research and literature in the field. The research makes a practical contribution to police agencies’ understanding of officer knowledge and police practice in ways that have the potential to shape education and training agendas, policy approaches around generalist versus specialist policing, strategic and operational strategy, as well as partnership engagements. The research also makes a theoretical contribution given that the research design is informed by the Three Circle

Acute illness is a risk factor for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterization laboratory

Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).

Gradual training of cascaded shape regression for facial landmark localization and pose estimation

Facial landmarks play an important role in face recognition. They serve different steps of the recognition such as pose estimation, face alignment, and local feature extraction. Recently, cascaded shape regression has been proposed to accurately locate facial landmarks. A large number of weak regressors are cascaded in a sequence to fit face shapes to the correct landmark locations. In this paper, we propose to improve the method by applying gradual training. With this training, the regressors are not directly aimed to the true locations. The sequence instead is divided into successive parts each of which is aimed to intermediate targets between the initial and the true locations. We also investigate the incorporation of pose information in the cascaded model. The aim is to find out whether the model can be directly used to estimate head pose. Experiments on the Annotated Facial Landmarks in the Wild database have shown that the proposed method is able to improve the localization and give accurate estimates of pose.

Letter : anxiety score as a risk factor for radial artery vasospasm during radial interventions : a pilot study

I read with interest the article in Angiology that determined the role of anxiety level on radial artery spasm during transradial coronary angiography.1 As the importance of conducting more randomised controlled trials using anxiolytics to define the relation between anxiety and vasospasm was noted by the authors, I offer the following insights for investigators to consider when conducting such research. While previous research has already identified that moderate procedural sedation and opioid analgesia reduces the incidence of vasospasm,2 the identification of risk factors in the present study is hypothesis generating as to how outcomes might be even further improved. It is possible that selectively applying either even more intensive sedation and analgesia or complementary non-pharmacological stress-reducing therapies, such as music therapy or visualisation and attentive behaviour, to patients ‘at-risk’ of vasospasm (women and those with high levels of anxiety prior to the procedure) might lead to even better patient outcomes...

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

Liveness detection based on 3D face shape analysis

In recent years face recognition systems have been applied in various useful applications, such as surveillance, access control, criminal investigations, law enforcement, and others. However face biometric systems can be highly vulnerable to spoofing attacks where an impostor tries to bypass the face recognition system using a photo or video sequence. In this paper a novel liveness detection method, based on the 3D structure of the face, is proposed. Processing the 3D curvature of the acquired data, the proposed approach allows a biometric system to distinguish a real face from a photo, increasing the overall performance of the system and reducing its vulnerability. In order to test the real capability of the methodology a 3D face database has been collected simulating spoofing attacks, therefore using photographs instead of real faces. The experimental results show the effectiveness of the proposed approach.

Investigation of Association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.

Study of leukemia inhibitory factor polymorphism within an Australian multiple sclerosis population

OBJECTIVE: To examine a polymorphism within the 3' untranslated region of the leukemia inhibitory factor gene for an association with multiple sclerosis within an Australian case-control population. METHODS: A test group of 121 unrelated multiple sclerosis patients, of Caucasian origin, and 121 controls, matched for ethnicity, sex and age (+/-5 years) were included in the study. The LIF 3' UTR StuI polymorphism was genotyped by restriction fragment length polymorphism analysis. Statistical analysis of genotype and allele frequencies included Hardy-Weinberg law and conventional contingency table analysis incorporating the standard chi-squared test for independence. RESULTS: Allelic and genotype frequencies did not demonstrate a significant association between the case and control groups for the tested LIF 3' UTR StuI polymorphism. CONCLUSION: The results indicate that the LIF 3' UTR StuI polymorphism is not associated with multiple sclerosis, however we cannot exclude the hypothesis that other polymorphic alleles of LIF could be implicated in MS susceptibility.

Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.

The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians

Essential hypertension (EH) is a common, multifactorial disorder likely to be influenced by multiple genes of modest effect. The methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation is functionally important, being strongly associated with reduced enzyme activity and increased plasma levels of homocysteine. Mild hyperhomocysteinemia is a known risk factor for cardiovascular disease (CVD) and hypothesised also to be involved in hypertension pathophysiology. The present study was performed to determine the prevalence of the 677T mutation in Australian Caucasian patients diagnosed with EH and to test whether the C677T variant is associated with the disorder. A case-control cohort, consisting of 250 EH patients and 250 age, sex and racially matched normotensive controls, were used for the association study. Comparison of C677T allele frequencies revealed a higher proportion of the mutant allele (T) in the EH group (40%) compared to unaffected controls (34%) (p=0.07). Furthermore, genotypic results indicated that the prevalence of the homozygous mutant genotype (T/T) in the affected group was higher than that of controls (14%:10%) (p=0.17). Interestingly, conditional logistic regression showed that the MTHFR C677T mutation conferred a mild, yet significant increase in risk of essential hypertension after adjusting for body mass index (odds ratio=1.57, 95% confidence interval: 1.04-2.37, p=0.03). These findings require further investigation in large independent samples, but suggest that essential hypertension, like CVD, may be mildly influenced by the MTHFR C677T variant.