Limbs detection and tracking of head-fixed mice for behavioral phenotyping using motion tubes and deep learning

The broad accessibility of affordable and reliable recording equipment and its relative ease of use has enabled neuroscientists to record large amounts of neurophysiological and behavioral data. Given that most of this raw data is unlabeled, great effort is required to adapt it for behavioral phenotyping or signal extraction, for behavioral and neurophysiological data, respectively. Traditional methods for labeling datasets rely on human annotators which is a resource and time intensive process, which often produce data that that is prone to reproducibility errors. Here, we propose a deep learning-based image segmentation framework to automatically extract and label limb movements from movies capturing frontal and lateral views of head-fixed mice. The method decomposes the image into elemental regions (superpixels) with similar appearance and concordant dynamics and stacks them following their partial temporal trajectory. These 3D descriptors (referred as motion cues) are used to train a deep convolutional neural network (CNN). We use the features extracted at the last fully connected layer of the network for training a Long Short Term Memory (LSTM) network that introduces spatio-temporal coherence to the limb segmentation. We tested the pipeline in two video acquisition settings. In the first, the camera is installed on the right side of the mouse (lateral setting). In the second, the camera is installed facing the mouse directly (frontal setting). We also investigated the effect of the noise present in the videos and the amount of training data needed, and we found that reducing the number of training samples does not result in a drop of more than 5% in detection accuracy even when as little as 10% of the available data is used for training

A graphical formalism for mixed multi-unit combinatorial auctions

Mixed multi-unit combinatorial auctions are auctions that allow participants to bid for bundles of goods to buy, for bundles of goods to sell, and for transformations of goods. The intuitive meaning of a bid for a transformation is that the bidder is offering to produce a set of output goods after having received a set of input goods. To solve such an auction the auctioneer has to choose a set of bids to accept and decide on a sequence in which to implement the associated transformations. Mixed auctions can potentially be employed for the automated assembly of supply chains of agents. However, mixed auctions can be effectively applied only if we can also ensure their computational feasibility without jeopardising optimality. To this end, we propose a graphical formalism, based on Petri nets, that facilitates the compact represention of both the search space and the solutions associated with the winner determination problem for mixed auctions. This approach allows us to dramatically reduce the number of decision variables required for solving a broad class of mixed auction winner determination problems. An additional major benefit of our graphical formalism is that it provides new ways to formally analyse the structural and behavioural properties of mixed auctions. © 2009 Springer Science+Business Media, LLC.This work was funded by the Jose Castillejo programme (JC2008-00337), IEA (TIN2006-15662-C02-01), OK (IST-4-027253-STP), eREP(EC-FP6-CIT5-28575) and Agreement Technologies (CONSOLIDER CSD2007-0022, INGENIO 2010)Peer Reviewe

Trust-Based Mechanisms for Robust and Efficient Task Allocation in the Presence of Execution Uncertainty

Vickrey-Clarke-Groves (VCG) mechanisms are often used to allocate tasks to selfish and rational agents. VCG mechanisms are incentive-compatible, direct mechanisms that are efficient (i.e. maximise social utility) and individually rational (i.e. agents prefer to join rather than opt out). However, an important assumption of these mechanisms is that the agents will always successfully complete their allocated tasks. Clearly, this assumption is unrealistic in many real-world applications where agents can, and often do, fail in their endeavours. Moreover, whether an agent is deemed to have failed may be perceived differently by different agents. Such subjective perceptions about an agent’s probability of succeeding at a given task are often captured and reasoned about using the notion of trust. Given this background, in this paper, we investigate the design of novel mechanisms that take into account the trust between agents when allocating tasks. Specifically, we develop a new class of mechanisms, called trust-based mechanisms, that can take into account multiple subjective measures of the probability of an agent succeeding at a given task and produce allocations that maximise social utility, whilst ensuring that no agent obtains a negative utility. We then show that such mechanisms pose a challenging new combinatorial optimisation problem (that is NP-complete), devise a novel representation for solving the problem, and develop an effective integer programming solution (that can solve instances with about 2×105 possible allocations in 40 seconds).

Trust-based mechanisms for robust and efficient task allocation in the presence of execution uncertainty

Vickrey-Clarke-Groves (VCG) mechanisms are often used to allocate tasks to selfish and rational agents. VCG mechanisms are incentive-compatible, direct mechanisms that are efficient (i.e. maximise social utility) and individually rational (i.e. agents prefer to join rather than opt out). However, an important assumption of these mechanisms is that the agents will always successfully complete their allocated tasks. Clearly, this assumption is unrealistic in many real-world applications where agents can, and often do, fail in their endeavours. Moreover, whether an agent is deemed to have failed may be perceived differently by different agents. Such subjective perceptions about an agent’s probability of succeeding at a given task are often captured and reasoned about using the notion of trust. Given this background, in this paper, we investigate the design of novel mechanisms that take into account the trust between agents when allocating tasks. Specifically, we develop a new class of mechanisms, called trust-based mechanisms, that can take into account multiple subjective measures of the probability of an agent succeeding at a given task and produce allocations that maximise social utility, whilst ensuring that no agent obtains a negative utility. We then show that such mechanisms pose a challenging new combinatorial optimisation problem (that is NP-complete), devise a novel representation for solving the problem, and develop an effective integer programming solution (that can solve instances with about 2×105 possible allocations in 40 seconds)

Prediagnostic adult body mass index change and esophageal adenocarcinoma survival

Background: We examined whether body mass index (BMI) changes in adulthood, prior to disease onset, are associated with overall survival among esophageal adenocarcinoma patients. Methods: We included 285 histologically confirmed patients with a complete baseline BMI questionnaire. Using extended Cox regression models, we obtained adjusted hazard ratios (HRs) for the associations between overall survival and BMI at diagnosis, BMI 6 months before diagnosis, self-reported average adult BMI, and ΔBMI (BMI 6 months before diagnosis minus average adult BMI), categorized into tertiles 25 and <35 kg/m2 was associated with better overall survival. Compared to patients with stable BMI in adulthood, patients who gained BMI throughout adulthood had 1.68 times the all-cause hazard of death (95% CI: 1.17-2.43; P <.01), independent of diagnosis BMI and percent weight loss 6 months before diagnosis. Compared to patients with average adult BMI < 27.5 who maintained stable adult BMI, patients with average adult BMI ≥ 27.5 kg/m2 who gained BMI had the worst survival (HR = 3.05; 95% CI 1.62-5.72; P <.01). Conclusion: Body mass index gain in adulthood is associated with poor overall survival, and maintaining a normal body weight throughout adulthood is associated with the best overall survival among esophageal adenocarcinoma patients, independent of BMI at diagnosis

Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data

In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data

Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample

PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. METHODS: A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. RESULTS: A total of 392 men (65.4 +/- 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 +/- 0.1 ng/ml) than in those with the CC-genotype (1.7 +/- 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 +/- 2.0 vs. 32 +/- 0.8 ml, P = 0.02) and lower PSA levels (1.6 +/- 0.3 vs. 1.9 +/- 0.1 ng/ml). CONCLUSIONS: The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameter

Metabolic Syndrome and Benign Prostatic Hyperplasia: Evidence of a Potential Relationship, Hypothesized Etiology, and Prevention

Benign prostatic hyperplasia (BPH) is highly prevalent in older men and causes substantial adverse effects on health. The pathogenesis of this disease is not totally clear. Recent reports have suggested a possible relationship between metabolic syndrome (MetS) and BPH. Single components of MetS (obesity, dyslipidemia, hypertension, and insulin resistance) as well as the syndrome itself may predispose patients to a higher risk of BPH and lower urinary tract symptoms (LUTS). This may stem from changes in insulin resistance, increased autonomic activity, impaired nitrergic innervation, increased Rho kinase activity, pro-inflammatory status, and changes in sex hormones that occur in association with MetS. However, the exact underlying mechanisms that regulate the potential relationship between MetS and BPH/LUTS still need to be clarified. Increased physical activity and dietary strategies may help in decreasing the incidence of MetS and its impact on BPH/LUTS. However, differences in the definitions used to address the examined predictors and endpoints preclude the possibility of arriving at definitive conclusions

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

El document inclou una pàgina final amb una correcció (corrigendum). Aquesta, per si sola, té el següent DOI: 10.1038/ncomms9739 i es va publicar al mateix vol. 6.Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies