On brain atlas choice and automatic segmentation methods: a comparison of MAPER & FreeSurfer using three atlas databases.

Several automatic image segmentation methods and few atlas databases exist for analysing structural T1-weighted magnetic resonance brain images. The impact of choosing a combination has not hitherto been described but may bias comparisons across studies. We evaluated two segmentation methods (MAPER and FreeSurfer), using three publicly available atlas databases (Hammers_mith, Desikan-Killiany-Tourville, and MICCAI 2012 Grand Challenge). For each combination of atlas and method, we conducted a leave-one-out cross-comparison to estimate the segmentation accuracy of FreeSurfer and MAPER. We also used each possible combination to segment two datasets of patients with known structural abnormalities (Alzheimer's disease (AD) and mesial temporal lobe epilepsy with hippocampal sclerosis (HS)) and their matched healthy controls. MAPER was better than FreeSurfer at modelling manual segmentations in the healthy control leave-one-out analyses in two of the three atlas databases, and the Hammers_mith atlas database transferred to new datasets best regardless of segmentation method. Both segmentation methods reliably identified known abnormalities in each patient group. Better separation was seen for FreeSurfer in the AD and left-HS datasets, and for MAPER in the right-HS dataset. We provide detailed quantitative comparisons for multiple anatomical regions, thus enabling researchers to make evidence-based decisions on their choice of atlas and segmentation method

Direct generation of photon triplets using cascaded photon-pair sources

Non-classical states of light, such as entangled photon pairs and number states, are essential for fundamental tests of quantum mechanics and optical quantum technologies. The most widespread technique for creating these quantum resources is the spontaneous parametric down-conversion (SPDC) of laser light into photon pairs. Conservation of energy and momentum in this process, known as phase-matching, gives rise to strong correlations which are used to produce two-photon entanglement in various degrees of freedom. It has been a longstanding goal of the quantum optics community to realise a source that can produce analogous correlations in photon triplets, but of the many approaches considered, none have been technically feasible. In this paper we report the observation of photon triplets generated by cascaded down-conversion. Here each triplet originates from a single pump photon, and therefore quantum correlations will extend over all three photons in a way not achievable with independently created photon pairs. We expect our photon-triplet source to open up new avenues of quantum optics and become an important tool in quantum technologies. Our source will allow experimental interrogation of novel quantum correlations, the post-selection free generation of tripartite entanglement without post- selection and the generation of heralded entangled-photon pairs suitable for linear optical quantum computing. Two of the triplet photons have a wavelength matched for optimal transmission in optical fibres, ideally suited for three-party quantum communication. Furthermore, our results open interesting regimes of non-linear optics, as we observe spontaneous down-conversion pumped by single photons, an interaction also highly relevant to optical quantum computing.Comment: 7 pages, 3 figures, 1 table; accepted by Natur

Online and social networking interventions for the treatment of depression in young people: a systematic review

BACKGROUND: Major depression accounts for the greatest burden of all diseases globally. The peak onset of depression occurs between adolescence and young adulthood, and for many individuals, depression displays a relapse-remitting and increasingly severe course. Given this, the development of cost-effective, acceptable, and population-focused interventions for depression is critical. A number of online interventions (both prevention and acute phase) have been tested in young people with promising results. As these interventions differ in content, clinician input, and modality, it is important to identify key features (or unhelpful functions) associated with treatment outcomes. OBJECTIVE: A systematic review of the research literature was undertaken. The review was designed to focus on two aspects of online intervention: (1) standard approaches evaluating online intervention content in randomized controlled designs (Section 1), and (2) second-generation online interventions and services using social networking (eg, social networking sites and online support groups) in any type of research design (Section 2). METHODS: Two specific literature searches were undertaken. There was no date range specified. The Section 1 search, which focused on randomized controlled trials, included only young people (12-25 years) and yielded 101 study abstracts, of which 15 met the review inclusion criteria. The Section 2 search, which included all study design types and was not restricted in terms of age, yielded 358 abstracts, of which 22 studies met the inclusion criteria. Information about the studies and their findings were extracted and tabulated for review. RESULTS: The 15 studies identified in Section 1 described 10 trials testing eight different online interventions, all of which were based on a cognitive behavioral framework. All but one of the eight identified studies reported positive results; however, only five of the 15 studies used blinded interviewer administered outcomes with most trials using self-report data. Studies varied significantly in presentation of intervention content, treatment dose, and dropout. Only two studies included moderator or clinician input. Results for Section 2 were less consistent. None of the Section 2 studies reported controlled or randomized designs. With the exception of four studies, all included participants were younger than 25 years of age. Eight of the 16 social networking studies reported positive results for depression-related outcomes. The remaining studies were either mixed or negative. Findings for online support groups tended to be more positive; however, noteworthy risks were identified. CONCLUSIONS: Online interventions with a broad cognitive behavioral focus appear to be promising in reducing depression symptomology in young people. Further research is required into the effectiveness of online interventions delivering cognitive behavioral subcomponents, such as problem-solving therapy. Evidence for the use of social networking is less compelling, although limited by a lack of well-designed studies and social networking interventions. A range of future social networking therapeutic opportunities are highlighted

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

Mass Spectrometry-Based (GeLC-MS/MS) Comparative Proteomic Analysis of Endoscopically (ePFT) Collected Pancreatic and Gastroduodenal Fluids

Objectives: The secretin-stimulated endoscopic pancreatic function test (ePFT) allows for the safe collection of gastroduodenal and pancreatic fluid from the duodenum. We test the hypothesis that these endoscopically collected fluids have different proteomes. As such, we aim to show that the ePFT method can be used to collect fluid enriched in pancreatic proteins to test for pancreatic function. Methods: Gastroduodenal and pancreatic fluid were collected sequentially from chronic pancreatitis patients undergoing an ePFT. Proteins from each fluid type were extracted using previously published optimized methods and subjected to GeLC-MS/MS analysis for protein identification and bioinformatics analysis. Results: Mass spectrometry analysis identified proteins that were exclusive in either gastroduodenal (46) or pancreatic fluid (234). Subsequent quantitative analysis revealed proteins that were differentially abundant with statistical significance. As expected, proteolytic enzymes and protease inhibitors were among the differentially detected proteins. The proteases pepsinogens and gastrin were enriched in gastroduodenal fluid, while common pancreatic enzymes (e.g., aminopeptidase N, chymotrypsin C, elastase-3A, trypsin, and carboxypeptidase A1, and elastase 2B) were found in greater abundance in pancreatic fluid. Similarly for protease inhibitors, members of the cystatin family were exclusive to gastroduodenal fluid, while serpins A11, B4, and D1 were exclusive to pancreatic fluid. Conclusions: We have shown that ePFT collection coupled with mass spectrometry can be used to identify differentially detected proteins in gastroduodenal and pancreatic fluids. The data obtained using GeLC-MS/MS techniques provide further evidence supporting the feasibility of using ePFT-collected fluid to study specific diseases of the upper gastrointestinal tract, such as chronic pancreatitis

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Biallelic mutations in IRF8 impair human NK cell maturation and function

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Objectum sexuality: a sexual orientation linked with autism and synaesthesia

Objectum-sexuality (OS) is a sexual orientation which has received little attention in the academic literature. Individuals who identify as OS experience emotional, romantic and/or sexual feelings towards inanimate objects (e.g. a bridge, a statue). We tested 34 OS individuals and 88 controls, and provide the first empirical evidence that OS is linked to two separate neurodevelopmental traits - autism and synaesthesia. We show that OS individuals possess significantly higher rates of diagnosed autism and significantly stronger autistic traits compared to controls, as well as a significantly higher prevalence of synaesthesia, and significant synaesthetic traits inherent in the nature of their attractions. Our results suggest that OS may encapsulate autism and synaesthesia within its phenomenology. Our data speak to debates concerning the biological underpinnings of sexuality, to models of autism and synaesthesia, and to psychological and philosophical models of romantic love