Functional magnetic resonance brain imaging of executive cognitive performance in young first-episode schizophrenia patients and age-matched long-term cannabis users

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like “negative” symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Potential-dependent surface-enhanced resonance raman spectroscopy at nanostructured TiO2 : A case study on cytochrome b5

Abstract: Nanostructured titanium dioxide (TiO2) electrodes, prepared by anodization of titanium, are employed to probe the electron-transfer process of cytochrome b5 (cyt b5) by surface-enhanced resonance Raman (SERR) spectroscopy. Concomitant with the increased nanoscopic surface roughness of TiO2, achieved by raising the anodization voltage from 10 to 20 V, the enhancement factor increases from 2.4 to 8.6, which is rationalized by calculations of the electric field enhancement. Cyt b 5 is immobilized on TiO2 under preservation of its native structure but it displays a non-ideal redox behavior due to the limited conductivity of the electrode material. The electron-transfer efficiency which depends on the crystalline phase of TiO2 has to be improved by appropriate doping for applications in bioelectrochemistry. Nanostructured TiO2 electrodes are employed to probe the electron-transfer process of cytochrome b5 by surface-enhanced resonance Raman spectroscopy. Concomitant with the increased nanoscopic surface roughness of TiO2, the enhancement factor increases, which can be attributed to the electric field enhancement. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Complementary surface-enhanced resonance raman spectroscopic biodetection of mixed protein solutions by chitosan- and silica-coated plasmon-tuned silver nanoparticles

Silver nanoparticles with identical plasmonic properties but different surface functionalities are synthesized and tested as chemically selective surface-enhanced resonance Raman (SERR) amplifiers in a two-component protein solution. The surface plasmon resonances of the particles are tuned to 413 nm to match the molecular resonance of protein heme cofactors. Biocompatible functionalization of the nanoparticles with a thin film of chitosan yields selective SERR enhancement of the anionic protein cytochrome b5, whereas functionalization with SiO2 amplifies only the spectra of the cationic protein cytochrome c. As a result, subsequent addition of the two differently functionalized particles yields complementary information on the same mixed protein sample solution. Finally, the applicability of chitosan-coated Ag nanoparticles for protein separation was tested by in situ resonance Raman spectroscopy.

Positive magnetic resonance imaging findings in the asymptomatic wrist

BACKGROUND: Magnetic resonance imaging (MRI) is being increasingly utilized to define pathology and guide treatment in patients presenting with wrist pain. The clinical relevance of MRI identified or confirmed pathology has not been established, and the prevalence of asymptomatic MRI pathology is not known. METHODS: Twenty volunteers with no previous wrist injury or symptoms underwent bilateral MRI wrist studies in this exploratory diagnostic study. The scans were reported by an experienced musculoskeletal radiologist and an experienced wrist surgeon, with a consensus reached on each report. RESULTS: There were 3.15 positive MRI findings per wrist. There were 126 positive findings (range 1-6 per wrist). Sixty-eight ganglia were identified. Eleven ligament tears or perforations were also identified. Increased joint fluid was seen at many sites, most frequently adjacent to the piso-triquetral joint. CONCLUSION: The accuracy of MRI in identifying triangular fibrocartilage complex tears, intercarpal ligament tears and carpal bone osteonecrosis is rapidly being refined. Positive MRI findings are common and may be coincidental in patients with wrist pain. MRI findings need to be correlated closely with clinical examination and history.

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Understanding Uncertainties in Non-Linear Population Trajectories: A Bayesian Semi-Parametric Hierarchical Approach to Large-Scale Surveys of Coral Cover

Recently, attempts to improve decision making in species management have focussed on uncertainties associated with modelling temporal fluctuations in populations. Reducing model uncertainty is challenging; while larger samples improve estimation of species trajectories and reduce statistical errors, they typically amplify variability in observed trajectories. In particular, traditional modelling approaches aimed at estimating population trajectories usually do not account well for nonlinearities and uncertainties associated with multi-scale observations characteristic of large spatio-temporal surveys. We present a Bayesian semi-parametric hierarchical model for simultaneously quantifying uncertainties associated with model structure and parameters, and scale-specific variability over time. We estimate uncertainty across a four-tiered spatial hierarchy of coral cover from the Great Barrier Reef. Coral variability is well described; however, our results show that, in the absence of additional model specifications, conclusions regarding coral trajectories become highly uncertain when considering multiple reefs, suggesting that management should focus more at the scale of individual reefs. The approach presented facilitates the description and estimation of population trajectories and associated uncertainties when variability cannot be attributed to specific causes and origins. We argue that our model can unlock value contained in large-scale datasets, provide guidance for understanding sources of uncertainty, and support better informed decision making

Exact parametric confidence intervals for Bland-Altman limits of agreement

Purpose The previous literature on Bland-Altman analysis only describes approximate methods for calculating confidence intervals for 95% Limits of Agreement (LoAs). This paper describes exact methods for calculating such confidence intervals, based on the assumption that differences in measurement pairs are normally distributed. Methods Two basic situations are considered for calculating LoA confidence intervals: the first where LoAs are considered individually (i.e. using one-sided tolerance factors for a normal distribution); and the second, where LoAs are considered as a pair (i.e. using two-sided tolerance factors for a normal distribution). Equations underlying the calculation of exact confidence limits are briefly outlined. Results To assist in determining confidence intervals for LoAs (considered individually and as a pair) tables of coefficients have been included for degrees of freedom between 1 and 1000. Numerical examples, showing the use of the tables for calculating confidence limits for Bland-Altman LoAs, have been provided. Conclusions Exact confidence intervals for LoAs can differ considerably from Bland and Altman’s approximate method, especially for sample sizes that are not large. There are better, more precise methods for calculating confidence intervals for LoAs than Bland and Altman’s approximate method, although even an approximate calculation of confidence intervals for LoAs is likely to be better than none at all. Reporting confidence limits for LoAs considered as a pair is appropriate for most situations, however there may be circumstances where it is appropriate to report confidence limits for LoAs considered individually.

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMGrecorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.

Magnetic resonance imaging: An accurate, radiation-free, alternative to computed tomography for the primary imaging and three-dimensional reconstruction of the bony orbit

Purpose: To determine the extent to which the accuracy of magnetic resonance imaging (MRI) based virtual 3-dimensional (3D) models of the intact orbit can approach that of the gold standard, computed tomography (CT) based models. The goal was to determine whether MRI is a viable alternative to CT scans in patients with isolated orbital fractures and penetrating eye injuries, pediatric patients, and patients requiring multiple scans in whom radiation exposure is ideally limited. Materials and Methods: Patients who presented with unilateral orbital fractures to the Royal Brisbane and Women’s Hospital from March 2011 to March 2012 were recruited to participate in this cross-sectional study. The primary predictor variable was the imaging technique (MRI vs CT). The outcome measurements were orbital volume (primary outcome) and geometric intraorbital surface deviations (secondary outcome)between the MRI- and CT-based 3D models. Results: Eleven subjects (9 male) were enrolled. The patients’ mean age was 30 years. On average, the MRI models underestimated the orbital volume of the CT models by 0.50 0.19 cm3 . The average intraorbital surface deviation between the MRI and CT models was 0.34 0.32 mm, with 78 2.7% of the surface within a tolerance of 0.5 mm. Conclusions: The volumetric differences of the MRI models are comparable to reported results from CT models. The intraorbital MRI surface deviations are smaller than the accepted tolerance for orbital surgical reconstructions. Therefore, the authors believe that MRI is an accurate radiation-free alternative to CT for the primary imaging and 3D reconstruction of the bony orbit. �

Single voxel Magnetic Resonance Spectroscopic (1H-MRS) analysis of deep brain structures after traumatic prefrontal brain injury (TBI) in rat

Chronic difficulties arising from mild brain injury (TBI) are difficult to predict because the processes underlying changes after TBI are poorly understood. In mild brain injury the extent of neuropsychiatric and cognitive symptoms correspond poorly to overt tissue loss (Barth 1983; Liu 2010). Cellular, immune and hormonal cascades occurring after injury and continuing during the healing process may impact uninjured brain regions sensitive to the effects of physiological and emotional stress, which receive projections from the injury site. Changes in these most basic properties due to injury or disease have profound implications for virtually every aspect of brain function through disruption of neurotransmitter, neuroendocrine and metabolic systems. In order to screen for changes in transmitter and metabolic activity, in this study we developed Single voxel proton Magnetic Resonance Spectroscopy (1H-MRS) for use in both injured and control animals. We first evaluated if 1H-MRS could be used to evaluate in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus in both control and injured animals after controlled cortical impact injury to the rat prefrontal cortex. We found that metabolite measurements for Myo-Inositol, Choline, creatine, Glutamate+Glutamine, and N-acetyl-acetate are attainable in deep brain structures in vivo in injured and controls rats. We next seek to evaluate longitudinally, in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus during the first month after controlled cortical impact injury to the rat prefrontal cortex. These ongoing studies will provide data on the changes in transmitters and metabolites over time in injured and non-injured subjects. These studies address some of the fundamental questions about how mild brain injury has such diverse effects on overall brain health and function.

A statistical model for combustion resonance from a DI diesel engine with applications

Introduced in this paper is a Bayesian model for isolating the resonant frequency from combustion chamber resonance. The model shown in this paper focused on characterising the initial rise in the resonant frequency to investigate the rise of in-cylinder bulk temperature associated with combustion. By resolving the model parameters, it is possible to determine: the start of pre-mixed combustion, the start of diffusion combustion, the initial resonant frequency, the resonant frequency as a function of crank angle, the in-cylinder bulk temperature as a function of crank angle and the trapped mass as a function of crank angle. The Bayesian method allows for individual cycles to be examined without cycle-averaging|allowing inter-cycle variability studies. Results are shown for a turbo-charged, common-rail compression ignition engine run at 2000 rpm and full load.

Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Tumour microenvironment greatly influences the development and metastasis of cancer progression. The development of three dimensional (3D) culture models which mimic that displayed in vivo can improve cancer biology studies and accelerate novel anticancer drug screening. Inspired by a systems biology approach, we have formed 3D in vitro bioengineered tumour angiogenesis microenvironments within a glycosaminoglycan-based hydrogel culture system. This microenvironment model can routinely recreate breast and prostate tumour vascularisation. The multiple cell types cultured within this model were less sensitive to chemotherapy when compared with two dimensional (2D) cultures, and displayed comparative tumour regression to that displayed in vivo. These features highlight the use of our in vitro culture model as a complementary testing platform in conjunction with animal models, addressing key reduction and replacement goals of the future. We anticipate that this biomimetic model will provide a platform for the in-depth analysis of cancer development and the discovery of novel therapeutic targets.

Use of parametric modelling and climate-based metrics for the efficient design of daylight strategies in buildings with complex geometries

The purpose of this research is to assess daylight performance of buildings with climatic responsive envelopes with complex geometry that integrates shading devices in the façade. To this end two case studies are chosen due to their complex geometries and integrated daylight devices. The effect of different parameters of the daylight devices is analysed through Climate base daylight metrics.