Building Disease Detection Algorithms with Very Small Numbers of Positive Samples

Although deep learning can provide promising results in medical image analysis, the lack of very large annotated datasets confines its full potential. Furthermore, limited positive samples also create unbalanced datasets which limit the true positive rates of trained models. As unbalanced datasets are mostly unavoidable, it is greatly beneficial if we can extract useful knowledge from negative samples to improve classification accuracy on limited positive samples. To this end, we propose a new strategy for building medical image analysis pipelines that target disease detection. We train a discriminative segmentation model only on normal images to provide a source of knowledge to be transferred to a disease detection classifier. We show that using the feature maps of a trained segmentation network, deviations from normal anatomy can be learned by a two-class classification network on an extremely unbalanced training dataset with as little as one positive for 17 negative samples. We demonstrate that even though the segmentation network is only trained on normal cardiac computed tomography images, the resulting feature maps can be used to detect pericardial effusion and cardiac septal defects with two-class convolutional classification networks

Loss of angiotensin II receptor expression in dopamine neurons in Parkinson’s disease correlates with pathological progression and is accompanied by increases in Nox4- and 8-OH guanosine-related nucleic acid oxidation and caspase-3 activation

In rodent models of Parkinsons disease (PD), dopamine neuron loss is accompanied by increased expression of angiotensin II (AngII), its type 1 receptor (AT1), and NADPH oxidase (Nox) in the nigral dopamine neurons and microglia. AT1 blockers (ARBs) stymie such oxidative damage and neuron loss. Whether changes in the AngII/AT1/Nox4 axis contribute to Parkinson neuropathogenesis is unknown. Here, we studied the distribution of AT1 and Nox4 in dopamine neurons in two nigral subregions: the less affected calbindin-rich matrix and the first-affected calbindin-poor nigrosome 1 of three patients, who were clinically asymptomatic, but had nigral dopamine cell loss and Braak stages consistent with a neuropathological diagnosis of PD (prePD). For comparison, five clinically- and neuropathologically-confirmed PD patients and seven age-matched control patients (AMC) were examined.AT1 and Nox4 immunoreactivity was noted in dopamine neurons in both the matrix and the nigrosome 1. The total cellular levels of AT1 in surviving dopamine neurons in the matrix and nigrosome 1 declined from AMC>prePD>PD, suggesting that an AngII/AT1/Nox4 axis orders neurodegenerative progression. In this vein, the loss of dopamine neurons was paralleled by a decline in total AT1 per surviving dopamine neuron. Similarly, AT1 in the nuclei of surviving neurons in the nigral matrix declined with disease progression, i.e., AMC>prePD>PD. In contrast, in nigrosome 1, the expression of nuclear AT1 was unaffected and similar in all groups. The ratio of nuclear AT1 to total AT1 (nuclear + cytoplasmic + membrane) in dopamine neurons increased stepwise from AMC to prePD to PD. The proportional increase in nuclear AT1 in dopamine neurons in nigrosome 1 of prePD and PD patients was accompanied by elevated nuclear expression of Nox4, oxidative damage to DNA, and caspase-3-mediated cell loss.Our observations are consistent with the idea that AngII/AT1/Nox4 axis-mediated oxidative stress gives rise to the dopamine neuron dysfunction and loss characteristic of the neuropathological and clinical manifestations of PD and suggest that the chance for a neuron to survive increases in association with lower total as well as nuclear AT1 expression. Our results support the need for further evaluation of ARBs as disease-modifying agents in PD

Detecting Hands in Egocentric Videos: Towards Action Recognition

Recently, there has been a growing interest in analyzing human daily activities from data collected by wearable cameras. Since the hands are involved in a vast set of daily tasks, detecting hands in egocentric images is an important step towards the recognition of a variety of egocentric actions. However, besides extreme illumination changes in egocentric images, hand detection is not a trivial task because of the intrinsic large variability of hand appearance. We propose a hand detector that exploits skin modeling for fast hand proposal generation and Convolutional Neural Networks for hand recognition. We tested our method on UNIGE-HANDS dataset and we showed that the proposed approach achieves competitive hand detection results

Opioid analgesia and the somatosensory memory of neonatal surgical injury in the adult rat

Background Nociceptive input during early development can produce somatosensory memory that influences future pain response. Hind-paw incision during the 1st postnatal week in the rat enhances re-incision hyperalgesia in adulthood. We now evaluate its modulation by neonatal analgesia. Methods Neonatal rats [Postnatal Day 3 (P3)] received saline, intrathecal morphine 0.1 mg kg−1 (IT), subcutaneous morphine 1 mg kg−1 (SC), or sciatic levobupivacaine block (LA) before and after plantar hind-paw incision (three×2 hourly injections). Six weeks later, behavioural thresholds and electromyography (EMG) measures of re-incision hyperalgesia were compared with an age-matched adult-only incision (IN) group. Morphine effects on spontaneous (conditioned place preference) and evoked (EMG sensitivity) pain after adult incision were compared with prior neonatal incision and saline or morphine groups. The acute neonatal effects of incision and analgesia on behavioural hyperalgesia at P3 were also evaluated. Results Adult re-incision hyperalgesia was not prevented by neonatal peri-incision morphine (saline, IT, and SC groups > IN; P<0.05–0.01). Neonatal sciatic block, but not morphine, prevented the enhanced re-incision reflex sensitivity in adulthood (LA < saline and morphine groups, P<0.01; LA vs IN, not significant). Morphine efficacy in adulthood was altered after morphine alone in the neonatal period, but not when administered with neonatal incision. Morphine prevented the acute incision-induced hyperalgesia in neonatal rats, but only sciatic block had a preventive analgesic effect at 24 h. Conclusions Long-term effects after neonatal injury highlight the need for preventive strategies. Despite effective analgesia at the time of neonatal incision, morphine as a sole analgesic did not alter the somatosensory memory of early-life surgical injury

Isolation and identification of the genera Acetobacter and Gluconobacter in coconut toddy (mnazi)

This study investigated the occurrence and identified the dominant spoilage genera of acetic acid bacteria in coconut wine (mnazi), by plating the dilution series previously pre-enriched in a basalmedium onto GYP agar, followed by physiological and biochemical tests. Both Acetobacter and Gluconobacter strains were Gram variable, oxidase negative and catalase positive. All Acetobacterstrains over-oxidized ethanol to acetic acid and finally to CO2 and H2O, while Gluconobacter were unable to oxidize acetic acid to CO2 and H2O. Acetobacter and Gluconobacter alike showed positivegrowth at 25, 30 and 40°C and also at pH 7.0 and 4.5, while there was no growth at 45°C, pH 2.5 and 8.5. Acetobacter strains oxidized both lactate and acetate while Gluconobacter oxidized lactate only. Bothgenera were unable to liquefy gelatin. Acetobacter showed negative growth at 15°C and also in peptone medium, while Gluconobacter showed positive growth both in peptone medium and at 15°C. Bothgenera were able to ferment arabinose, xylose, ribose, glucose, galactose, mannose and melibiose and unable to ferment amylagdine, cellibiose, esculine, lactose, maltose, mannitol, melezitose, Nagluconate, raffinose, rhamnose and salicine. The Acetobacter and Gluconobacter strains isolated in this study were found to be responsible for the spoilage of mnazi

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

Excitation dependent Fano-like interference effects in plasmonic silver nanorods

Surface plasmon resonances in metal nanoparticles are an emerging technology platform for nano-optics applications from sensing to solar energy conversion. The electromagnetic near field associated with these resonances arises from modes determined by the shape, size, and composition of the metal nanoparticle. When coupled in the near field, multiple resonant modes can interact to give rise to interference effects offering fine control of both the spectral response and spatial distribution of fields near the particle. Here, we present an examination of experimental electron energy loss spectroscopy (EELS) of silver nanorod monomer surface plasmon modes and present an explanation of observed spatial amplitude modulation of the Fabry-Pérot resonance modes of these silver nanorods using electrodynamics simulations. For these simulations, we identify differences in spectral peak symmetry in light scattering and electron spectroscopies (EELS and cathodoluminescence) and analyze the distinct near-field responses of silver nanorods to plane-wave light and electron beam excitation in terms of a coupled oscillator model. Effects of properties of the material and the incident field are evaluated, and the spatially resolved EELS signals are shown to provide a signature for assessing Fano-like interference effects in silver nanorods. These findings outline key considerations and challenges for interpreting electron microscopy data on plasmonic nanoparticles for understanding nanoscale optics and for characterization and design of photonic devices.S.M.C. acknowledges support of a Gates Cambridge Scholarship. D.R. acknowledges support from the Royal Society's Newton International Fellowship scheme. We acknowledge the use of computing facilities provided by CamGrid. Parts of this work were also performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. We thank F.J. de la Peña for helpful discussions on the use of hyperspy. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (Grant No. FP7/2007-2013)/ERC Grant Agreement No. 291522-3DIMAGE. Data on rod “B” were acquired by one of us (D. Rossouw) with support of a NSERC Discovery Grant (G. A. Botton) at the Canadian Centre for Electron Microscopy, a national facility supported by NSERC and McMaster University. We thank G. A. Botton for access to data on rod “B” and for helpful comments on this manuscript. P.A.M. also acknowledges funding from the European Union's Seventh Framework Program under a contract for an Integrated Infrastructure Initiative (Reference No. 312483-ESTEEM2)

Socially defeated male rats display a blunted adrenocortical response to a low dose of 8-OH-DPAT

The study examined in male Wistar rats the influence of social defeat on the neuroendocrine stress response system using injection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), as the pharmacological challenge. Social defeat was defined by the submissive postures displayed by the Wistar rats which were threatened and attacked by Tryon Maze Dull S3 rats for 10 min. 18-20 h after social defeat, the defeated rats were injected intravenously (i.v.) with a low and high dose of 8-OH-DPAT in their home cages. Blood samples were withdrawn from the freely moving cannulated rats for determination of plasma corticosterone and catecholamines. The corticosterone response to the low dose of 8-OH-DPAT (0.05 mg/kg, i.v.) was significantly diminished in the defeated rats as compared to the controls, but this dose failed to affect catecholamine concentrations. The high dose of 8-OH-DPAT (0.15 mg/kg, i.v.) significantly elevated corticosterone and adrenaline levels in defeated and control rats to the same extent, whereas no effect on noradrenaline was found. The present data thus indicate that social defeat blunts 5-HT1A receptor-mediated adrenocortical activation probably via a decrease in the sensitivity of a population of postsynaptic 5-HT receptors

Randomized planning of dynamic motions avoiding forward singularities

The final publication is available at link.springer.comForward singularities, also known as direct, or actuator singularities, cause many problems to the planning and control of robot motions. They yield position errors and rigidity losses of the robot, and generate unbounded actions in typical control laws. To circumvent these issues, this paper proposes a randomized kinodynamic planner for computing trajectories avoiding such singularities. Given initial and final states for the robot, the planner attempts to connect them by means of a dynamically-feasible, singularity-free trajectory that also respects the force limits of the actuators. The performance of the strategy is illustrated in simulation by means of a parallel robot performing a highly- dynamic task.Peer ReviewedPostprint (author's final draft