The accurate staging of ovarian cancer using 3T magnetic resonance imaging - a realistic option

Objectives: The aim of the study was to determine whether staging primary ovarian cancer using 3.0 Tesla (3T) magnetic resonance imaging (MRI) is comparable to surgical staging of the disease. Design: A retrospective study consisting of a search of the pathology database to identify women with ovarian pathology from May 2004 to January 2007. Setting: All women treated for suspected ovarian cancer in our cancer centre region. Sample: All women suspected of ovarian pathology who underwent 3T MRI prior to primary surgical intervention between May 2004 and January 2007. Methods: All women found to have ovarian pathology, both benign and malignant, were then cross checked with the magnetic resonance (MR) database to identify those who had undergone 3T MRI prior to surgery. The resulting group of women underwent comparison of the MR, surgical and histopathological findings for each individual including diagnosis of benign or malignant disease and International Federation of Gynecology and Obstetrics (FIGO) staging where appropriate. Main outcome measures: Comparisons were made between the staging accuracy of 3T MRI and surgical staging compared with histopathological findings and FIGO stage using weighted kappa. Sensitivity, specificity and accuracy were calculated for diagnosing malignant ovarian disease with 3T MRI. Results: A total of 191 women identified as having ovarian pathology underwent imaging with 3T MR and primary surgical intervention. In 19 of these women, the ovarian disease was an incidental finding. The group for which staging methods were compared consisted of 77 women of primary ovarian malignancy (20 of whom had borderline tumours). 3T MRI was able to detect ovarian malignancy with a sensitivity of 92% and a specificity of 76%. The overall accuracy in detecting malignancy with 3T MRI was 84%, with a positive predictive value of 80% and negative predictive value of 90%. Statistical analysis of the two methods of staging using weighted kappa, gave a K value of 0.926 (SE ±0.121) for surgical staging and 0.866 (SE ±0.119) for MR staging. A further analysis of the staging data for ovarian cancers alone, excluding borderline tumours resulted in a K value of 0.931 (SE ±0.136) for histopathological staging versus MR staging and 0.958 (±0.140) for histopathological stage versus surgical staging. Conclusion: Our study has shown that MRI can achieve staging of ovarian cancer comparable with the accuracy seen with surgical staging. No previous studies comparing different modalities have used the higher field strength 3T MRI. In addition, all other studies comparing radiological assessment of ovarian cancer have grouped the stages into I, II, III and IV rather than the more clinically appropriate a, b and c subgroups. © 2008 The Authors

Hybrid Elastic ARM&Cloud HPC Collaborative Platform for generic tasks

Compute-heavy workloads are currently run on Hybrid HPC structures using x86 CPUs and GPUs from Intel, AMD, or NVidia, which have extremely high energy and financial costs. However, thanks to the incredible progress made on CPUs and GPUs based on the ARM architecture and their ubiquity in today’s mobile devices, it’s possible to conceive of a low-cost solution for our world’s data processing needs. Every year ARM-based mobile devices become more powerful, efficient, and come in ever smaller packages with ever growing storage. At the same time, smartphones waste these capabilities at night while they’re charging. This represents billions of idle devices whose processing power is not being utilized. For that reason, the objective of this paper is to evaluate and develop a hybrid, distributed, scalable, and redundant platform that allows for the utilization of these idle devices through a cloud-based administration service. The system would allow for massive improvements in terms of efficiency and cost for com-pute-heavy workload. During the evaluation phase, we were able to establish savings in power and cost significant enough to justify exploring it as a serious alternative to traditional computing architectures.Instituto de Investigación en Informátic

ICRPfinder: a fast pattern design algorithm for coding sequences and its application in finding potential restriction enzyme recognition sites

<p>Abstract</p> <p>Background</p> <p>Restriction enzymes can produce easily definable segments from DNA sequences by using a variety of cut patterns. There are, however, no software tools that can aid in gene building -- that is, modifying wild-type DNA sequences to express the same wild-type amino acid sequences but with enhanced codons, specific cut sites, unique post-translational modifications, and other engineered-in components for recombinant applications. A fast DNA pattern design algorithm, ICRPfinder, is provided in this paper and applied to find or create potential recognition sites in target coding sequences.</p> <p>Results</p> <p>ICRPfinder is applied to find or create restriction enzyme recognition sites by introducing silent mutations. The algorithm is shown capable of mapping existing cut-sites but importantly it also can generate specified new unique cut-sites within a specified region that are guaranteed not to be present elsewhere in the DNA sequence.</p> <p>Conclusion</p> <p>ICRPfinder is a powerful tool for finding or creating specific DNA patterns in a given target coding sequence. ICRPfinder finds or creates patterns, which can include restriction enzyme recognition sites, without changing the translated protein sequence. ICRPfinder is a browser-based JavaScript application and it can run on any platform, in on-line or off-line mode.</p

Chemoinformatic Consideration of Novel Psychoactive Substances: Compilation and Preliminary Analysis of a Categorised Dataset

Recent years have seen the emergence into circulation of a growing array of novel psychoactive substances (NPS). Knowledge of the pharmacological profiles and risk liability of these compounds is typically very scarce. Development of chemoinformatic tools enabling prediction of properties within uncharacterised analogues has potential be of particular use. In order to facilitate this, compilation of a chemical inventory comprising known NPS is a necessity. Sourcing a variety of published governmental and analytical reports, a dataset composed of 690 distinct acknowledged NPS, complete with defined chemical structures, has been constructed. This is supplemented by a complementary series of 155 established psychoactive drugs of abuse (EPDA). Classification was performed in accordance with their key molecular structural features, subjective effect profiles and pharmacological mechanisms of action. In excess of forty chemical groupings, spanning seven subjective effect categories and six broad mechanisms of pharmacological action, were identified. Co-occurrence of NPS and EPDA within specific classes was common, showcasing inherent scope both for chemical read-across and for the derivation of structural alerts

Good perceived sleep quality protects against the raised risk of respiratory infection during sleep restriction in young adults.

Study Objectives: Prospectively examine the association between sleep restriction, perceived sleep quality (PSQ) and upper respiratory tract infection (URTI). Methods: In 1318 military recruits (68% males) self-reported sleep was assessed at the beginning and end of a 12-week training course. Sleep restriction was defined as an individualized reduction in sleep duration of ≥2 hours/night compared with civilian life. URTIs were retrieved from medical records. Results: On commencing training, approximately half of recruits were sleep restricted (52%; 2.1 ± 1.6 h); despite the sleep debt, 58% of recruits with sleep restriction reported good PSQ. Regression adjusted for covariates showed that recruits commencing training with sleep restriction were more likely to suffer URTI during the course (OR = 2.93, 95% CI 1.29–6.69, p = .011). Moderation analysis showed this finding was driven by poor PSQ (B = −1.12, SE 0.50, p = .023), as no significant association between sleep restriction and URTI was observed in recruits reporting good PSQ, despite a similar magnitude of sleep restriction during training. Associations remained in the population completing training, accounting for loss to follow-up. Recruits reporting poor PSQ when healthy at the start and end of training were more susceptible to URTI (OR = 3.16, 95% CI 1.31–7.61, p = .010, vs good PSQ). Conclusion: Good perceived sleep quality was associated with protection against the raised risk of respiratory infection during sleep restriction. Studies should determine whether improvements in sleep quality arising from behavioral sleep interventions translate to reduced respiratory infection during sleep restriction

Maximum Photosynthetic Yield of Green Microalgae in Photobioreactors

The biomass yield on light energy of Dunaliella tertiolecta and Chlorella sorokiniana was investigated in a 1.25- and 2.15-cm light path panel photobioreactor at constant ingoing photon flux density (930 µmol photons m−2 s−1). At the optimal combination of biomass density and dilution rate, equal biomass yields on light energy were observed for both light paths for both microalgae. The observed biomass yield on light energy appeared to be based on a constant intrinsic biomass yield and a constant maintenance energy requirement per gram biomass. Using the model of Pirt (New Phytol 102:3–37, 1986), a biomass yield on light energy of 0.78 and 0.75 g mol photons−1 and a maintenance requirement of 0.0133 and 0.0068 mol photons g−1 h−1 were found for D. tertiolecta and C. sorokiniana, respectively. The observed yield decreases steeply at low light supply rates, and according to this model, this is related to the increase of the amount of useable light energy diverted to biomass maintenance. With this study, we demonstrated that the observed biomass yield on light in short light path bioreactors at high biomass densities decreases because maintenance requirements are relatively high at these conditions. All our experimental data for the two strains tested could be described by the physiological models of Pirt (New Phytol 102:3–37, 1986). Consequently, for the design of a photobioreactor, we should maintain a relatively high specific light supply rate. A process with high biomass densities and high yields at high light intensities can only be obtained in short light path photobioreactors

A long view of liberal peace and its crisis

The ‘crisis’ of liberal peace has generated considerable debate in International Relations. However, analysis is inhibited by a shared set of spatial, cultural and temporal assumptions that rest on and reproduce a problematic separation between self-evident ‘liberal’ and ‘non-liberal’ worlds, and locates the crisis in presentist terms of the latter’s resistance to the former’s expansion. By contrast, this article argues that efforts to advance liberal rule have always been interwoven with processes of alternative order-making, and in this way are actively integral, not external, to the generation of the subjectivities, contestations, violence and rival social orders that are then apprehended as self-evident obstacles and threats to liberal peace and as characteristic of its periphery. Making visible these intimate relations of co-constitution elided by representations of liberal peace and its crisis requires a long view and an analytical frame that encompasses both liberalism and its others in the world. The argument is developed using a Foucauldian governmentality framework and illustrated with reference to Sri Lanka

Development and validation of an improved algorithm for overlaying flexible molecules

A program for overlaying multiple flexible molecules has been developed. Candidate overlays are generated by a novel fingerprint algorithm, scored on three objective functions (union volume, hydrogen-bond match, and hydrophobic match), and ranked by constrained Pareto ranking. A diverse subset of the best ranked solutions is chosen using an overlay-dissimilarity metric. If necessary, the solutions can be optimised. A multi-objective genetic algorithm can be used to find additional overlays with a given mapping of chemical features but different ligand conformations. The fingerprint algorithm may also be used to produce constrained overlays, in which user-specified chemical groups are forced to be superimposed. The program has been tested on several sets of ligands, for each of which the true overlay is known from protein–ligand crystal structures. Both objective and subjective success criteria indicate that good results are obtained on the majority of these sets

Measuring symmetry, asymmetry and randomness in neural network connectivity

Cognitive functions are stored in the connectome, the wiring diagram of the brain, which exhibits non-random features, so-called motifs. In this work, we focus on bidirectional, symmetric motifs, i.e. two neurons that project to each other via connections of equal strength, and unidirectional, non-symmetric motifs, i.e. within a pair of neurons only one neuron projects to the other. We hypothesise that such motifs have been shaped via activity dependent synaptic plasticity processes. As a consequence, learning moves the distribution of the synaptic connections away from randomness. Our aim is to provide a global, macroscopic, single parameter characterisation of the statistical occurrence of bidirectional and unidirectional motifs. To this end we define a symmetry measure that does not require any a priori thresholding of the weights or knowledge of their maximal value. We calculate its mean and variance for random uniform or Gaussian distributions, which allows us to introduce a confidence measure of how significantly symmetric or asymmetric a specific configuration is, i.e. how likely it is that the configuration is the result of chance. We demonstrate the discriminatory power of our symmetry measure by inspecting the eigenvalues of different types of connectivity matrices. We show that a Gaussian weight distribution biases the connectivity motifs to more symmetric configurations than a uniform distribution and that introducing a random synaptic pruning, mimicking developmental regulation in synaptogenesis, biases the connectivity motifs to more asymmetric configurations, regardless of the distribution. We expect that our work will benefit the computational modelling community, by providing a systematic way to characterise symmetry and asymmetry in network structures. Further, our symmetry measure will be of use to electrophysiologists that investigate symmetry of network connectivity

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway