High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring

Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30–40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation

Quasirandom permutations are characterized by 4-point densities

For permutations π and τ of lengths |π|≤|τ| , let t(π,τ) be the probability that the restriction of τ to a random |π| -point set is (order) isomorphic to π . We show that every sequence {τj} of permutations such that |τj|→∞ and t(π,τj)→1/4! for every 4-point permutation π is quasirandom (that is, t(π,τj)→1/|π|! for every π ). This answers a question posed by Graham

An improved method for surface immobilisation of RNA: application to small Non-Coding RNA - mRNA pairing

Characterisation of RNA and its intermolecular interactions is increasing in importance as the inventory of known RNA functions continues to expand. RNA-RNA interactions are central to post-transcriptional gene regulation mechanisms in bacteria, and the interactions of bacterial small non-coding RNAs (sRNAs) with their mRNA targets are the subject of much current research. The technology of surface plasmon resonance (SPR) is an attractive approach to studying these interactions since it is highly sensitive, and allows interaction measurements to be recorded in real-time. Whilst a number of approaches exist to label RNAs for surface-immobilisation, the method documented here is simple, quick, efficient, and utilises the high-affinity streptavidin-biotin interaction. Specifically, we ligate a biotinylated nucleotide to the 3' end of RNA using T4 RNA ligase. Although this is a previously recognised approach, we have optimised the method by our discovery that the incorporation of four or more adenine nucleotides at the 3' end of the RNA (a poly-A-tail) is required in order to achieve high ligation efficiencies. We use this method within the context of investigating small non-coding RNA (sRNA)-mRNA interactions through the application of surface technologies, including quantitative SPR assays. We first focus on validating the method using the recently characterised Escherichia coli sRNA-mRNA pair, MicA-ompA, specifically demonstrating that the addition of the poly-A-tail to either RNA does not affect its subsequent binding interactions with partner molecules. We then apply this method to investigate the novel interactions of a Vibrio cholerae Qrr sRNA with partner mRNAs, hapR and vca0939; RNA-RNA pairings that are important in mediating pathogenic virulence. The calculated binding parameters allow insights to be drawn regarding sRNA-mRNA interaction mechanisms

Automated analysis and benchmarking of GCMC simulation programs in application to gas adsorption.

<p>In this work we set out to evaluate the computational performance of several popular Monte Carlo simulation programs, namely Cassandra, DL Monte, Music, Raspa and Towhee, in modelling gas adsorption in crystalline materials. We focus on the reference case of adsorption in IRMOF-1 at 208 K. To critically assess their performance, we first establish some criteria which allow us to make this assessment on a consistent basis. Specifically, the total computational time required for a program to complete a simulation of an adsorption point, consists of the time required for equilibration plus time required to generate a specific number of uncorrelated samples of the property of interest. Our analysis shows that across different programs there is a wide difference in the statistical value of a single MC step, however their computational performance is quite comparable. We further explore the use of energy grids and energy bias techniques, as well as the efficiency of the parallel execution of the simulations. The test cases developed are made openly available as a resource for the community, and can be used for validation and as a template for further studies.</p

The critical window for the classical Ramsey-Tur\'an problem

The first application of Szemer\'edi's powerful regularity method was the following celebrated Ramsey-Tur\'an result proved by Szemer\'edi in 1972: any K_4-free graph on N vertices with independence number o(N) has at most (1/8 + o(1)) N^2 edges. Four years later, Bollob\'as and Erd\H{o}s gave a surprising geometric construction, utilizing the isoperimetric inequality for the high dimensional sphere, of a K_4-free graph on N vertices with independence number o(N) and (1/8 - o(1)) N^2 edges. Starting with Bollob\'as and Erd\H{o}s in 1976, several problems have been asked on estimating the minimum possible independence number in the critical window, when the number of edges is about N^2 / 8. These problems have received considerable attention and remained one of the main open problems in this area. In this paper, we give nearly best-possible bounds, solving the various open problems concerning this critical window.Comment: 34 page

A critical review of the epidemiological evidence of effects of air pollution on dementia, cognitive function and cognitive decline in adult population

Dementia is arguably the most pressing public health challenge of our age. Since dementia does not have a cure,identifying risk factors that can be controlled has become paramount to reduce the personal, societal and eco-nomic burden of dementia. The relationship between exposure to air pollution and effects on cognitive function,cognitive decline and dementia has stimulated increasing scientific interest in the past few years. This review ofthe literature critically examines the available epidemiological evidence of associations between exposure to am-bient air pollutants, cognitive performance, acceleration of cognitive decline, risk of developing dementia, neuro-imaging and neurological biomarker studies, following Bradford Hill guidelines for causality.The evidence reviewed has been consistent in reporting associations between chronic exposure to air pollutionand reduced global cognition, as well as impairment in specific cognitive domains including visuo-spatial abili-ties. Cognitive decline and dementia incidence have also been consistently associated with exposure to air pollu-tion. The neuro-imaging studies reviewed report associations between exposure to air pollution and whitematter volume reduction. Other reported effects include reduction in gray matter, larger ventricular volume,and smaller corpus callosum. Findings relating to ischemic (white matter hyperintensities/silent cerebralinfarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease have been heteroge-neous, as have observations on hippocampal volume and air pollution. The few studies available on neuro-inflammation tend to report associations with exposure to air pollution. everal effect modifiers have been suggested in the literature, but more replication studies are required. Tradi-tional confounding factors have been controlled or adjusted for in most of the reviewed studies. Additional con-founding factors have also been considered, but the inclusion of these has varied among the different studies.Despite all the efforts to adjust for confounding factors, residual confounding cannot be completely ruled out, es-pecially since the factors affecting cognition and dementia are not yet fully understood.The available evidence meets many of the Bradford Hill guidelines for causality. The reported associations be-tween a range of air pollutants and effects oncognitive function in older people,including the acceleration of cog-nitive decline and the induction of dementia, are likely to be causal in nature.However, the diversity of study designs, air pollutants and endpoints examined precludes the attribution of theseadverse effects to a single class of pollutant and makes meta-analysis inappropriate

3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

We thank the EPSRC (EP/H009744/1) and Wellcome Trust DOH (HICF-0510-080) for fundin

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

An examination of autism spectrum traits in adolescents with anorexia nervosa and their parents

There may be a link between anorexia nervosa and autism spectrum disorders. The aims of this study were to examine whether adolescents with anorexia nervosa have autism spectrum and/or obsessive-compulsive traits, how many would meet diagnostic criteria for autism spectrum disorder, and whether these traits are shared by parents

An examination of the clinical outcomes of adolescents and young adults with broad autism spectrum traits and autism spectrum disorder and anorexia nervosa: A multi centre study

Objectives: To compare the clinical outcomes of adolescents and young adults with anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD traits. Method: The developmental and well‐being assessment and social aptitude scale were used to categorize adolescents and young adults with AN (N = 149) into those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria for a possible/probable ASD (N = 6). We compared both eating disorders specific measures and broader outcome measures at intake and 12 months follow‐up. Results: Those with ASD traits had significantly more inpatient/day‐patient service use (p = .015), as well as medication use (p < .001) at baseline. Both groups had high social difficulties and poorer global functioning (strengths and difficulties questionnaire) at baseline, which improved over time but remained higher at 12 months in the ASD traits group (p = .002). However, the improvement in eating disorder symptoms at 12 months was similar between groups with or without ASD traits. Treatment completion rates between AN only and ASD traits were similar (80.1 vs. 86.5%). Discussion: Adolescents with AN and ASD traits show similar reductions in their eating disorder symptoms. Nevertheless, their social difficulties remain high suggesting that these are life‐long difficulties rather than starvation effects