Mice behaviorally selected for high Pavlovian fear memory exhibit fear generalization, HPA-axis alterations and increased basal activity in cortico-limbic circuits

Biological factors underlying individual variability in fearfulness and anxiety have important implications for stress-related psychiatric illness including PTSD and major depression. Using an advanced intercross line (AIL) derived from C57BL/6 and DBA/2J mouse strains and behavioral selection over 3 generations, we established two lines exhibiting High or Low fear behavior after fear conditioning. Across the selection generations, the two lines showed clear differences in training and tests for contextual and conditioned fear. Before fear conditioning training, there were no differences between lines in baseline freezing to a novel context. However, after fear conditioning High line mice demonstrated pronounced freezing in a new context suggestive of poor context discrimination. Fear generalization was not restricted to contextual fear. High fear mice froze to a novel acoustic stimulus while freezing in the Low line did not increase over baseline. Enhanced fear learning and generalization are consistent with transgenic and pharmacological disruption of the hypothalamic-pituitary-adrenal axis (HPA-axis) (Brinks, 2009, Thompson, 2004, Kaouane, 2012). To determine whether there were differences in HPA-axis regulation between the lines, morning urine samples were collected to measure basal corticosterone. Levels of secreted corticosterone in the circadian trough were analyzed by corticosterone ELISA. High fear mice were found to have higher basal corticosterone levels than low line animals. Examination of hormonal stress response components by qPCR revealed increased expression of CRH mRNA and decreased mRNA for MR and CRHR1 in hypothalamus of high fear mice. These alterations may contribute to both the behavioral phenotype and higher basal corticosterone in High fear mice. To determine basal brain activity in vivo in High and Low fear mice we used manganese-enhanced magnetic resonance imaging (MEMRI). Analysis revealed a pattern of basal brain activity made up of amygdala, cortical and hippocampal circuits that was elevated in the High line. Ongoing studies also seek to determine the relative balance of excitatory and inhibitory tone in the amygdala and hippocampus and the neuronal structure of its neurons. While these heterogeneous lines are selected on fear memory expression, HPA-axis alterations and differences in hippocampal activity segregate with the behavioral phenotypes. These differences are detectable in a basal state strongly suggesting these are biological traits underlying the behavioral phenotype (Johnson et al, 2011).

Applying digital product memories in industrial production

Industrial production and supply chains face increased demands for mass customization and tightening regulations on the traceability of goods, leading to higher requirements concerning flexibility, adaptability, and transparency of processes. Technologies for the ’Internet of Things' such as smart products and semantic representations pave the way for future factories and supply chains to fulfill these challenging market demands. In this chapter a backend-independent approach for information exchange in open-loop production processes based on Digital Product Memories DPMs is presented. By storing order-related data directly on the item, relevant lifecycle information is attached to the product itself. In this way, information handover between several stages of the value chain with focus on the manufacturing phase of a product has been realized. In order to report best practices regarding the application of DPM in the domain of industrial production, system prototype implementations focusing on the use case of producing and handling a smart drug case are illustrated.

Antioxidant responses to an acute ultra-endurance exercise: Impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase

Antioxidant requirements have neither been defined for endurance nor been defined for ultra-endurance athletes. To verify whether an acute bout of ultra-endurance exercise modifies the need for nutritive antioxidants, we aimed (1) to investigate the changes of endogenous and exogenous antioxidants in response to an Ironman triathlon; (2) to particularise the relevance of antioxidant responses to the indices of oxidatively damaged blood lipids, blood cell compounds and lymphocyte DNA and (3) to examine whether potential time-points of increased susceptibility to oxidative damage are associated with alterations in the antioxidant status. Blood that was collected from forty-two well-trained male athletes 2 d pre-race, immediately post-race, and 1, 5 and 19 d later was sampled. The key findings of the present study are as follows: (1) Immediately post-race, vitamin C, alpha-tocopherol, and levels of the Trolox equivalent antioxidant capacity, the ferric reducing ability of plasma and the oxygen radical absorbance capacity (ORAC) assays increased significantly. Exercise-induced changes in the plasma antioxidant capacity were associated with changes in uric acid, bilirubin and vitamin C. (2) Significant inverse correlations between ORAC levels and indices of oxidatively damaged DNA immediately and 1 d post-race suggest a protective role of the acute antioxidant responses in DNA stability. (3) Significant decreases in carotenoids and gamma-tocopherol 1 d post-race indicate that the antioxidant intake during the first 24 h of recovery following an acute ultra-endurance exercise requires specific attention. Furthermore, the present study illustrates the importance of a diversified and well-balanced diet to maintain a physiological antioxidant status in ultra-endurance athletes in reference to recommendations.

Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~ 100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity.

Can biophilic urbanism deliver strong economic and social benefits in cities? An economic and policy invetigations into the increased use of natural elements in urban design

Biophilic urbanism, or urban design that reflects humanity’s innate need for nature, stands to make significant contributions to a range of national, state and local government policies related to climate change mitigation and adaptation, by investigating ways in which nature can be integrated into, around and on top of buildings. Potential benefits of such design include reducing the heat island effect, reducing energy consumption for thermal control, enhancing urban biodiversity, improving well being and productivity, improving water cycle management, and assisting in the response to growing needs for densification and revitalisation of cities. This report will give an overview of the concept of biophilia and consider enablers and disablers to its application to urban planning and design. The paper will present findings from stakeholder engagement and a series of detailed case studies, related to a consideration of the economics of the use of biophilic elements (direct and indirect).

Assessing specific deterrence effects of increased speeding penalties using four measures of recidivism

Traffic law enforcement sanctions can impact on road user behaviour through general and specific deterrence mechanisms. The manner in which specific deterrence can influence recidivist behaviour can be conceptualised in different ways. While any reduction in speeding will have road safety benefits, the ways in which a ‘reduction’ is determined deserves greater methodological attention and has implications for countermeasure evaluation more generally. The primary aim of this research was to assess the specific deterrent impact of penalty increases for speeding offences in Queensland, Australia, in 2003 on two cohorts of drivers detected for speeding prior to and after the penalty changes were investigated. Since the literature is relatively silent on how to assess recidivism in the speeding context, the secondary research aim was to contribute to the literature regarding ways to conceptualise and measure specific deterrence in the speeding context. We propose a novel way of operationalising four measures which reflect different ways in which a specific deterrence effect could be conceptualised: (1) the proportion of offenders who re-offended in the follow up period; (2) the overall frequency of re-offending in the follow up period; (3) the length of delay to re-offence among those who re-offended; and (4) the average number of re-offences during the follow up period among those who re-offended. Consistent with expectations, results suggested an absolute deterrent effect of penalty changes, as evidenced by significant reductions in the proportion of drivers who re-offended and the overall frequency of re-offending, although effect sizes were small. Contrary to expectations, however, there was no evidence of a marginal specific deterrent effect among those who re-offended, with a significant reduction in the length of time to re-offence and no significant change in the average number of offences committed. Additional exploratory analyses investigating potential influences of the severity of the index offence, offence history, and method of detection revealed mixed results. Access to additional data from various sources suggested that the main findings were not influenced by changes in speed enforcement activity, public awareness of penalty changes, or driving exposure during the study period. Study limitations and recommendations for future research are discussed with a view to promoting more extensive evaluations of penalty changes and better understanding of how such changes may impact on motorists’ perceptions of enforcement and sanctions, as well as on recidivist behaviour.

Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis

Objective: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population. Methods: 673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/ homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy-Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case-control analysis. Results: HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI (HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001). Conclusions: HLA-627 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-β27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.

Cardiovascular disease is increased prior to onset of rheumatoid arthritis but not osteoarthritis: The population-based Nord-Trøndelag health study (HUNT)

Introduction: Patients with rheumatoid arthritis (RA) have increased risk of cardiovascular (CV) events. We sought to test the hypothesis that due to increased inflammation, CV disease and risk factors are associated with increased risk of future RA development. Methods: The population-based Nord-Trøndelag health surveys (HUNT) were conducted among the entire adult population of Nord-Trøndelag, Norway. All inhabitants 20 years or older were invited, and information was collected through comprehensive questionnaires, a clinical examination, and blood samples. In a cohort design, data from HUNT2 (1995-1997, baseline) and HUNT3 (2006-2008, follow-up) were obtained to study participants with RA (n = 786) or osteoarthritis (n = 3,586) at HUNT3 alone, in comparison with individuals without RA or osteoarthritis at both times (n = 33,567). Results: Female gender, age, smoking, body mass index, and history of previous CV disease were associated with self-reported incident RA (previous CV disease: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CV disease were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.23-2.36)) or restricting the analysis to cases with a hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.13-2.74)). History of previous CV disease was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). Conclusion: A history of previous CV disease was associated with increased risk of incident RA but not osteoarthritis.

Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure

AIM: This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. MATERIALS AND METHODS: A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. RESULTS: The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated samples and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. CONCLUSIONS: This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques.

Increased risk of emergency hospital admissions for children with renal diseases during heatwaves in Brisbane, Australia

Background Heatwaves have a significant impact on population health including both morbidity and mortality. In this study we examined the association between heatwaves and emergency hospital admissions (EHAs) for renal diseases in children (aged 0–14 years) in Brisbane, Australia. Methods Daily data on EHAs for renal diseases in children and exposure to temperature and air pollution were obtained for Brisbane city from January 1, 1996 to December 31, 2005. A time-stratified case-crossover design was used to compare the risks for renal diseases between heatwave and non-heatwave periods. Results There were 1565 EHAs for renal diseases in children during the study period. Heatwaves exhibited a significant impact on EHAs for renal diseases in children after adjusting for confounding factors (odds ratio: 3.6; 95% confidence interval: 1.4–9.5). The risk estimates differed with lags and the use of different heatwave definitions. Conclusions There was a significant increase in EHAs for renal diseases in children during heatwaves in Brisbane, a subtropical city where people are well accustomed to warm weather. This finding may have significant implications for pediatric renal care, particularly in subtropical and tropical regions.

Grant application: QUT Learning and Teaching scheme 2012 Cracking the Code - A checklist to complement CRAs for first year Justice students.

Widening participation brings with it increasing diversity, increased variation in the level of academic preparedness (Clarke, 2011; Nelson, Clarke, & Kift 2010). Cultural capital coupled with negotiating the academic culture creates an environment based on many assumptions about academic writing and university culture. Variations in staff and student expectations relating to the teaching and learning experience is captured in a range of national and institutional data (AUSSE, CEQ, LEX). Nationally, AUSSE data (2009) indicates that communication, writing, speaking and analytic skills, staff expectations are quite a bit higher than students. The research team noted a recognisable shift in the changing cohort of students and their understanding and engagement with feedback and CRAs, as well as variations in teaching staff and student expectations. The current reality of tutor and student roles is that: - Students self select when/how they access lectures and tutorials. - Shorter tutorial times result in reduced opportunity to develop rapport with students. - CRAs are not always used consistently by staff (different marking styles and levels of feedback). - Marking is not always undertaken by the student’s tutor/lecturer. - Student support services might be recommended to students once a poor grade has been given. Students can perceive this as remedial and a further sense of failure. - CRA sheet has a mark /grade attached to it. Stigma attached to low mark. Hard to focus on the CRA feedback with a poor mark etched next to it. - Limited opportunities for sessionals to access professional development to assist with engaging students and feedback. - FYE resources exist, however academic time is a factor in exploring and embedding these resources. Feedback is another area with differing expectations and understandings. Sadler (2009) contends that students are not equipped to decode the statements properly. For students to be able to apply feedback, they need to understand the meaning of the feedback statement. They also need to identify, the particular aspects of their work that need attention. The proposed Checklist/guide would be one page and submitted with each assessment piece thereby providing an interface to engage students and tutors in managing first year understandings and expectations around CRAs, feedback, and academic practice.

Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Free vibration of a kinked cantilever with attached masses

In this paper free vibration characteristics of a centrally kinked cantilever beam of unit mass carrying masses at the kink (m(k)) and at the tip (m(t)) are analyzed. Frequency factors are presented for the first two modes for different combinations of m(k),m(t) and the kink angle delta. A relationship of the form f(m(k),m(t), delta) = m(k) + m(t)(4 + 10/3 cos delta+ 2/3 cos(2) delta)=const appears to give the same fundamental frequency for a given delta and different combinations of [m(k), m(t)]. Mode shapes as well as bending moments at the support and at the kink are also discussed. The utility of a discrete beam model in understanding the free vibration characteristics is also highlighted.

Ship Seakeeping Operability, Motion Control, and Autonomy - A Bayesian Perspective

Ship seakeeping operability refers to the quantification of motion performance in waves relative to mission requirements. This is used to make decisions about preferred vessel designs, but it can also be used as comprehensive assessment of the benefits of ship-motion-control systems. Traditionally, operability computation aggregates statistics of motion computed over over the envelope of likely environmental conditions in order to determine a coefficient in the range from 0 to 1 called operability. When used for assessment of motion-control systems, the increase of operability is taken as the key performance indicator. The operability coefficient is often given the interpretation of the percentage of time operable. This paper considers an alternative probabilistic approach to this traditional computation of operability. It characterises operability not as a number to which a frequency interpretation is attached, but as a hypothesis that a vessel will attain the desired performance in one mission considering the envelope of likely operational conditions. This enables the use of Bayesian theory to compute the probability of that this hypothesis is true conditional on data from simulations. Thus, the metric considered is the probability of operability. This formulation not only adheres to recent developments in reliability and risk analysis, but also allows incorporating into the analysis more accurate descriptions of ship-motion-control systems since the analysis is not limited to linear ship responses in the frequency domain. The paper also discusses an extension of the approach to the case of assessment of increased levels of autonomy for unmanned marine craft.