Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome

 Objective: To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays aff ected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. Design, patients and setting: A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. Main outcome measures: Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. Results: 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically signifi cant diff erence in allhospital admission rates (95% CI for the diff erence, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the diff erence, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the diff erence, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the diff erence, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically signifi cant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the diff erence, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change signifi cantly (95% CI for the diff erence, - 1.5% to 0.8%; P = 0.43). Conclusion: The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no signifi cant change in rates of invasive treatment or inhospital mortality.

Determining the sensitivity of the Antarctic amphipod Orchomenella pinguides to metals using a joint model of survival response to exposure concentration and duration

Developing water quality guidelines for Antarctic marine environments requires understanding the sensitivity of local biota to contaminant exposure. Antarctic invertebrates have shown slower contaminant responses in previous experiments compared to temperate and tropical species in standard toxicity tests. Consequently, test methods which take into account environmental conditions and biological characteristics of cold climate species need to be developed. This study investigated the effects of five metals on the survival of a common Antarctic amphipod, Orchomenella pinguides. Multiple observations assessing mortality to metal exposure were made over the 30 days exposure period. Traditional toxicity tests with quantal data sets are analysed using methods such as maximum likelihood regression (probit analysis) and Spearman–Kärber which treat individual time period endpoints independently. A new statistical model was developed to integrate the time-series concentration–response data obtained in this study. Grouped survival data were modelled using a generalized additive mixed model (GAMM) which incorporates all the data obtained from multiple observation times to derive time integrated point estimates. The sensitivity of the amphipod, O. pinguides, to metals increased with increasing exposure time. Response times varied for different metals with amphipods responding faster to copper than to cadmium, lead or zinc. As indicated by 30 days lethal concentration (LC50) estimates, copper was the most toxic metal (31 µg/L), followed by cadmium (168 µg/L), lead (256 µg/L) and zinc (822 µg/L). Nickel exposure (up to 1.12 mg/L) did not affect amphipod survival. Using longer exposure durations and utilising the GAMM model provides an improved methodology for assessing sensitivities of slow responding Antarctic marine invertebrates to contaminants.

Photoreceptor topography and spectral sensitivity in the common brushtail possum (Trichosurus vulpecula)

Marsupials are believed to be the only non-primate mammals with both trichromatic and dichromatic color vision. The diversity of color vision systems present in marsupials remains mostly unexplored. Marsupials occupy a diverse range of habitats, which may have led to considerable variation in the presence, density, distribution, and spectral sensitivity of retinal photoreceptors. In this study we analyzed the distribution of photoreceptors in the common brushtail possum (Trichosurus vulpecula). Immunohistochemistry in wholemounts revealed three cone subpopulations recognized within two spectrally distinct cone classes. Long-wavelength sensitive (LWS) single cones were the largest cone subgroup (67-86%), and formed a weak horizontal visual streak (peak density 2,106 ± 435/mm2) across the central retina. LWS double cones were strongly concentrated ventrally (569 ± 66/mm2), and created a "negative" visual streak (134 ± 45/mm2) in the central retina. The strong regionalization between LWS cone topographies suggests differing visual functions. Short-wavelength sensitive (SWS) cones were present in much lower densities (3-10%), mostly located ventrally (179 ± 101/mm2). A minority population of cones (0-2.4%) remained unlabeled by both SWS- and LWS-specific antibodies, and may represent another cone population. Microspectrophotometry of LWS cone and rod visual pigments shows peak spectral sensitivities at 544 nm and 500 nm, respectively. Cone to ganglion cell convergences remain low and constant across the retina, thereby maintaining good visual acuity, but poor contrast sensitivity during photopic vision. Given that brushtail possums are so strongly nocturnal, we hypothesize that their acuity is set by the scotopic visual system, and have minimized the number of cones necessary to serve the ganglion cells for photopic vision.

Context sensitivity in action decreases along the autism spectrum: a predictive processing perspective

Recent predictive processing accounts of perception and action point towards a key challenge for the nervous system in dynamically optimizing the balance between incoming sensory information and existing expectations regarding the state of the environment. Here, we report differences in the influence of the preceding sensory context on motor function, varying with respect to both clinical and subclinical features of autism spectrum disorder (ASD). Reach-to-grasp movements were recorded subsequent to an inactive period in which illusory ownership of a prosthetic limb was induced. We analysed the sub-components of reach trajectories derived using a minimum-jerk fitting procedure. Non-clinical adults low in autistic features showed disrupted movement execution following the illusion compared to a control condition. By contrast, individuals higher in autistic features (both those with ASD and non-clinical individuals high in autistic traits) showed reduced sensitivity to the presence of the illusion in their reaching movements while still exhibiting the typical perceptual effects of the illusion. Clinical individuals were distinct from non-clinical individuals scoring high in autistic features, however, in the early stages of movement. These results suggest that the influence of high-level representations of the environment differs between individuals, contributing to clinical and subclinical differences in motor performance that manifest in a contextual manner. As high-level representations of context help to explain fluctuations in sensory input over relatively longer time scales, more circumscribed sensitivity to prior or contextual information in autistic sensory processing could contribute more generally to reduced social comprehension, sensory impairments and a stronger desire for predictability and routine.

The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity.

Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis.

Sensitivity to MK-801 in phospholipase C-β1 knockout mice reveals a specific NMDA receptor deficit

Phospholipase C-β1 (PLC-β1) is a critical component of multiple signalling pathways downstream of neurotransmitter receptors. Mice lacking this enzyme display a striking behavioural phenotype with relevance to human psychiatric disease. Glutamatergic dysfunction is strongly associated with several abnormal behavioural states and may underlie part of the phenotype of the phospholipase C-β1 knockout (KO) mouse. A heightened response to glutamatergic psychotomimetic drugs is a critical psychosis-related endophenotype, and in this study it was employed as a correlate of glutamatergic dysfunction. Control (n=8) and PLC-β1 KO mice (n=6) were treated with MK-801, a NMDA receptor (NMDAR) antagonist, following either standard housing or environmental enrichment, and the motor function and locomotor activity thus evoked was assessed. In addition, MK-801 binding to the NMDAR was evaluated through radioligand autoradiography in post-mortem tissue (on a drug-naive cohort). We have demonstrated a significantly increased sensitivity to the effects of the NMDA antagonist MK-801 in the PLC-β1 KO mouse. In addition, we found that this mouse line displays reduced hippocampal NMDAR expression, as measured by radioligand binding. We previously documented a reversal of specific phenotypes in this mouse line following housing in an enriched environment. Enrichment did not alter this heightened MK-801 response, nor NMDAR expression, indicating that this therapeutic intervention works on specific pathways only. These findings demonstrate the critical role of the glutamatergic system in the phenotype of the PLC-β1 KO mouse and highlight the role of these interconnected signalling pathways in schizophrenia-like behavioural disruption. These results also shed further light on the capacity of environmental factors to modulate subsets of these phenotypes.

Sprint interval and moderate-intensity continuous training have equal benefits on aerobic capacity, insulin sensitivity, muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in obese men

Key points: Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals. We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men. We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25 ± 1 years, BMI 34.8 ± 0.9 kg m-2) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ∼65% V˙O2 peak , 5 times per week) or constant load SIT (4-7 constant workload intervals of 200% Wmax 3 times per week). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine1177 phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Maximal aerobic capacity (V˙O2 peak ), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser1177 phosphorylation in terminal arterioles and capillaries (P < 0.05), but the latter effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microvascular endothelial NOX2 content (P < 0.05) and both increased capillary density and capillary-fibre perimeter exchange index (P < 0.05). In parallel, SIT and MICT increased V˙O2 peak (P < 0.05) and whole body insulin sensitivity (P < 0.05), and reduced central artery stiffness (P < 0.05). As no significant differences were observed between SIT and MICT it is concluded that SIT is a time efficient alternative to MICT to improve aerobic capacity, insulin sensitivity and muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in young obese men.

The use of kernel density estimation to examine associations between neighborhood destination intensity and walking and physical activity

BACKGROUND: Local destinations have previously been shown to be associated with higher levels of both physical activity and walking, but little is known about how the distribution of destinations is related to activity. Kernel density estimation is a spatial analysis technique that accounts for the location of features relative to each other. Using kernel density estimation, this study sought to investigate whether individuals who live near destinations (shops and service facilities) that are more intensely distributed rather than dispersed: 1) have higher odds of being sufficiently active; 2) engage in more frequent walking for transport and recreation. METHODS: The sample consisted of 2349 residents of 50 urban areas in metropolitan Melbourne, Australia. Destinations within these areas were geocoded and kernel density estimates of destination intensity were created using kernels of 400m (meters), 800m and 1200m. Using multilevel logistic regression, the association between destination intensity (classified in quintiles Q1(least)-Q5(most)) and likelihood of: 1) being sufficiently active (compared to insufficiently active); 2) walking≥4/week (at least 4 times per week, compared to walking less), was estimated in models that were adjusted for potential confounders. RESULTS: For all kernel distances, there was a significantly greater likelihood of walking≥4/week, among respondents living in areas of greatest destinations intensity compared to areas with least destination intensity: 400m (Q4 OR 1.41 95%CI 1.02-1.96; Q5 OR 1.49 95%CI 1.06-2.09), 800m (Q4 OR 1.55, 95%CI 1.09-2.21; Q5, OR 1.71, 95%CI 1.18-2.48) and 1200m (Q4, OR 1.7, 95%CI 1.18-2.45; Q5, OR 1.86 95%CI 1.28-2.71). There was also evidence of associations between destination intensity and sufficient physical activity, however these associations were markedly attenuated when walking was included in the models. CONCLUSIONS: This study, conducted within urban Melbourne, found that those who lived in areas of greater destination intensity walked more frequently, and showed higher odds of being sufficiently physically active-an effect that was largely explained by levels of walking. The results suggest that increasing the intensity of destinations in areas where they are more dispersed; and or planning neighborhoods with greater destination intensity, may increase residents' likelihood of being sufficiently active for health.

An integration of attachment theory and reinforcement sensitivity theory as a conceptual framework for understanding trauma

 The research examined the associations between Reinforcement Sensitivity Theory, Attachment Theory, and trauma symptoms among victims of interpersonal violence. Findings demonstrated a link between attachment, threat sensitivity, and trauma symptoms, indicating that RST and Attachment Theory provides a useful theoretical framework to understand how interpersonal violence contributes to psychological trauma.

Is the relationship between sensory-processing sensitivity and negative affect mediated by emotional regulation?

© 2015 Australian Psychological Society. Objective: Sensory-processing sensitivity refers to a trait-like difference in the extent to which individuals strongly and deeply process a variety of stimuli in the environment. While being highly sensitive has been linked to increased experiences of distress, the reasons for this are not well known. One potential mediator of this effect is emotional regulation-the set of processes influencing which emotions we have, when we have them, and how we experience and express them. This study therefore aimed to investigate whether sensory processing sensitivity is linked to negative affect via emotional regulation processes. Method: N=157 participants (n=118 females) completed online questionnaires assessing negative affect, sensory-processing sensitivity, along with two multidimensional emotional regulation measures. Results: An individual's lack of access to emotional regulation strategies, greater awareness of emotion, and lack of acceptance towards feeling distressed, acted as partial mediators between sensory-processing sensitivity and symptoms of depression. Combinations of these variables also partially mediated the relationship between sensory-processing sensitivity and symptoms of anxiety and stress. Conclusions: It is suggested that repeatedly experiencing aversive sensory-states among those with increased sensory-processing sensitivity impacts on their general awareness and acceptance of internal states and the confidence that one can regulate them. This in turn leads to the experience of negative affective states. Limitations of the present study and implications for therapeutic interventions are discussed.

Sensitivity of the final properties of tailored hot stamping components to the process and material parameters

The final mechanical properties of hot stamped components are affected by many process and material parameters due to the multidisciplinary nature of this thermal-mechanical-metallurgical process. The phase transformation, which depends on the temperature field and history, determines the final microstructure and consequently the final mechanical properties. Tailored hot stamping parts - where the cooling rates are locally chosen to achieve structures with graded properties - has been increasingly adopted in the automotive industry. In this case, the robustness of final part properties is more critical than in the conventional hot stamping parts, where the part is fully quenched. In this study, a wide range of input parameters in a generalized hot stamping model have been investigated, examining the effect on the temperature history and resulting final material properties. A generic thermo-mechanical finite element model of hot stamping was created and a modified phase transformation model, based on Scheil's additive principle, has been applied. The comparison between modeling and experiments shows that the modified phase transformation model coupled with the incubation time provides higher accuracy on the simulation of transformation kinetics history. The robustness of four conditions relevant to tailored hot stamping was investigated: heated tooling (with low and high tool conductance), air cooling, and conventional hot stamping. The results show the high robustness of the conventional hot stamping compared to tailored hot stamping, with respect to the stamped component's final material properties (i.e. phase fraction and hardness). Furthermore, tailored hot stamping showed higher robustness when low conductivity tools are used relative to high conductivity tools.

Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study

AIM/HYPOTHESIS: Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes. METHODS: Participants with stable glucose control commenced a randomized cross-over study involving four months of AA (2×500mg/day) or placebo supplementation. Insulin sensitivity was assessed using a hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures (2',7'-dichlorofluorescin [DCFH] oxidation, ratio of reduced-to-oxidized glutathione [GSH/GSSG] and F2-Isoprostanes) and insulin-stimulated measures (DCFH oxidation). Antioxidant concentrations, citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 (SVCT2), total Akt and phosphorylated Akt (ser473) were also measured in muscle samples. RESULTS: AA supplementation significantly increased insulin-mediated glucose disposal (delta rate of glucose disappearance; ∆Rd) (p=0.009), peripheral insulin-sensitivity index (p=0.046), skeletal muscle AA concentration (p=0.017) and muscle SVCT2 protein expression (p=0.008); but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia (p=0.007) when compared with placebo. Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo (p=0.006). Basal oxidative stress markers, citrate synthase activity, endogenous glucose production, HbA1C and muscle Akt expression were not significantly altered by AA supplementation. CONCLUSIONS/INTERPRETATION: In summary, oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes. Findings implicate AA supplementation as a potentially inexpensive, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.

Topic model kernel classification with probabilistically reduced features

Probabilistic topic models have become a standard in modern machine learning to deal with a wide range of applications. Representing data by dimensional reduction of mixture proportion extracted from topic models is not only richer in semantics interpretation, but could also be informative for classification tasks. In this paper, we describe the Topic Model Kernel (TMK), a topicbased kernel for Support Vector Machine classification on data being processed by probabilistic topic models. The applicability of our proposed kernel is demonstrated in several classification tasks with real world datasets. TMK outperforms existing kernels on the distributional features and give comparative results on nonprobabilistic data types.