An evaluation of active noise control in a cylindrical shell

The physical mechanisms governing the use of active noise control in an extended volume of a cylindrical shell are discussed. Measured data was compared with computer results from a previously derived analytical model based on an infinite shell theory. For both the analytical model and experiment, the radiation of the external monopoles is coupled to the internal acoustic field through the radial displacement of the thin, elastic cylindrical shell. An active noise control system was implemented in the cylinder using a fixed array of discrete monopole sources, all of which lie in the plane of the exterior noise sources. Good agreement between measurement and prediction was obtained for both internal pressure response and overall noise reduction. Attenuations in the source plane greater than 15 dB were recorded along with a uniformly quieted noise environment over the entire length of the experimental model. Results indicate that for extended axial forcing distributions or very low shell damping, axial arrays of control sources may be required. Finally, the Nyquist criteria for the number of azimuthal control sources is shown to provide for effective control over the full cylinder cross section

Hadron therapy information sharing prototype

The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form designs. The system as presented is ready for use in a clinical setting, and amenable to further customization. The essential contribution of the work reported here lies in the novel data integration and reporting methods, as well as the approach to software sustainability achieved through the use of community-supported open-source components

Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease:a pharmacogenetic study

The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system

Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

Components of acquisition-to-acquisition variance in continuous arterial spin labelling (CASL) imaging

<p>Abstract</p> <p>Background</p> <p>Images of perfusion estimates obtained with the continuous arterial spin labelling technique are characterized by variation between single acquisitions. Little is known about the spatial determinants of this variation during the acquisition process and their impact on voxel-by-voxel estimates of effects.</p> <p>Results</p> <p>We show here that the spatial patterns of covariance between voxels arising during the acquisition of these images uncover distinct mechanisms through which this variance arises: through variation in global perfusion levels; through the action of large vessels and other, less well characterized, large anatomical structures; and through the effect of noisy areas such as the edges of the brain.</p> <p>Conclusions</p> <p>Knowledge of these covariance patterns is important to experimenters for a correct interpretation of findings, especially for studies where relatively few acquisitions are made.</p

Interactions between cigarette and alcohol consumption in rural China

The objective of this paper is to analyze interdependencies between cigarette and alcohol consumption in rural China, using panel data for 10 years (1994–2003) for rural areas of 26 Chinese provinces. There have been many studies in which cigarette and alcohol consumption have been considered separately but few to date for China on interactions between the consumption of these two products. Taxes are often recommended as a tool to reduce alcohol and cigarette consumption. If cigarettes and alcohol are complements, taxing one will reduce the consumption of both and thus achieve a double public health dividend. However, if they are substitutes, taxing one will induce consumers to increase consumption of the other, offsetting the public health benefits of the tax. Our results indicate that the demands for both cigarettes and alcohol are very sensitive to the price of alcohol, but not to the price of cigarettes or to income. This suggests that taxes on alcohol can have a double dividend. On the other hand, an increase in cigarette taxes may not be effective in curbing cigarette or alcohol consumption in rural China

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37

Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces:state versus trait vulnerability markers of depression in bipolar disorder

Background - Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Methods - Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results - The BD versus HC showed significantly greater right amygdala-OFC FC (p = .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). Conclusions - In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC–FA relationships in BD and HC require further study

Geographical imagination and technological connectivity in East Africa

The paper analyses and compares two transformative moments of technologically-mediated change in East Africa, the construction of the Uganda railway between Mombasa and Lake Victoria (1896-1903) and the introduction of fibre-optic cables that landed into the ports of Dar Es Salaam and Mombasa in 2009. It uses discourse analysis to examine how technologically-mediated connectivity has been represented by political and economic actors during these transformative moments. In both cases, we explore the origins of the expectations of connectivity and the hope and fear associated with them. Building on Massey’s notion of power-geometry and Sheppard’s concept of positionality the paper focuses on power relationships in discussions of connectivity and asks how people understand the abilities of transformative technologies to modify positionalities and alter relational distance and proximity. Ultimately, by examining historical and contemporary expectations of connectivity in East Africa, this paper allows us to work towards creating more grounded and historicised understandings of the coming-together of technology and connectivity

Evaluating the Effect of Tissue Anisotropy on Brain Tumor Growth using a Mechanically-coupled Reaction-Diffusion Model

Glioblastoma (GBM), the most frequent malignant brain tumor in adults, is char- acterized by rapid growth and healthy tissue invasion. Long-term prognosis for GBM remains poor with median overall survival between 1 y to 2 y [15]. GBM presents with different growth phenotypes, ranging from invasive tumors without notable mass-effect to strongly displacing lesions. Biomechanical forces, such as those resulting from displacive tumor growth, shape the tumor environment and contribute to tumor progression [9]. We present an extended version of a mechanically–coupled reaction-diffusion model of brain tu- mor growth [1] that simulates tumor evolution over time and across different brain regions using literature-based parameter estimates for tumor cell proliferation, as well as isotropic motility, and mechanical tissue properties. This model yielded realistic estimates of the mechanical impact of a growing tumor on intra-cranial pressure. However, comparison to imaging data showed that asymmetric shapes could not be reproduced by isotropic growth assumptions. We modified this model to account for structural tissue anisotropy which is known to affect the directionality of tumor cell migration and may influence the mechanical behavior of brain tissue. Tumors were seeded at multiple locations in a human MR-DTI brain atlas and their spatio-temporal evolution was simulated using the Finite-Element Method. We evaluated the impact of tissue anisotropy on the model’s ability to reproduce the aspherical shapes of real pathologies by comparing predicted lesions to publicly available GBM imaging data. We found the impact on tumor shape to be strongly location dependent and highest for tumors located in brain regions that are characterized by a single dominant white matter direction, such as the corpus callosum. However, despite strongly anisotropic growth assumptions, all simulated tumors remained more spherical than real lesions at the corresponding location and similar volume. This finding is in agreement with previous studies [17, 6] suggesting that anisotropic cell migration along white matter fiber tracks is not a major determinant of tumor shape in the setting of reaction-diffusion based tumor growth models and for most locations across the brain