Learning Deep Features for Robotic Inference from Physical Interactions

In order to effectively handle multiple tasks that are not pre-defined, a robotic agent needs to automatically map its high-dimensional sensory inputs into useful features. As a solution, feature learning has empirically shown substantial improvements in obtaining representations that are generalizable to different tasks, compared to feature engineering approaches, but it requires a large amount of data and computational capacity. These challenges are specifically relevant in robotics due to the low signal-to-noise ratios inherent to robotic data, and to the cost typically associated with collecting this type of input. In this paper, we propose a deep probabilistic method based on Convolutional Variational Auto-Encoders (CVAEs) to learn visual features suitable for interaction and recognition tasks. We run our experiments on a self-supervised robotic sensorimotor dataset. Our data was acquired with the iCub humanoid and is based on a standard object collection, thus being readily extensible. We evaluated the learned features in terms of usability for 1) object recognition, 2) capturing the statistics of the effects, and 3) planning. In addition, where applicable, we compared the performance of the proposed architecture with other state-ofthe-art models. These experiments demonstrate that our model is capable of capturing the functional statistics of action and perception (i.e. images) which performs better than existing baselines, without requiring millions of samples or any handengineered features

Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC)

Funding for PEAC MRC: Grant code 36661. Funding Infrastructure support to EMR, Arthritis Research UK Experimental Treatment Centre: Grant code 20022

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades).UnpublishedTrondheim, Norway4.4. Scenari e mitigazione del rischio ambientaleope

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades)

The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour necrosis factor inhibitors in psoriatic arthritis patients with inadequate response to conventional therapy

Objective. To evaluate costs, benefits and cost–effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment

Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands

<p>Abstract</p> <p>Background</p> <p>The peptide CART is widely expressed in central and peripheral neurons, as well as in endocrine cells. Known peripheral sites of expression include the gastrointestinal (GI) tract, the pancreas, and the adrenal glands. In rodent pancreas CART is expressed both in islet endocrine cells and in nerve fibers, some of which innervate the islets. Recent data show that CART is a regulator of islet hormone secretion, and that CART null mutant mice have islet dysfunction. CART also effects GI motility, mainly via central routes. In addition, CART participates in the regulation of the hypothalamus-pituitary-adrenal-axis. We investigated CART expression in porcine pancreas, GI-tract, adrenal glands, and thyroid gland using immunocytochemistry.</p> <p>Results</p> <p>CART immunoreactive (IR) nerve cell bodies and fibers were numerous in pancreatic and enteric ganglia. The majority of these were also VIP IR. The finding of intrinsic CART containing neurons indicates that pancreatic and GI CART IR nerve fibers have an intrinsic origin. No CART IR endocrine cells were detected in the pancreas or in the GI tract. The adrenal medulla harboured numerous CART IR endocrine cells, most of which were adrenaline producing. In addition CART IR fibers were frequently seen in the adrenal cortex and capsule. The capsule also contained CART IR nerve cell bodies. The majority of the adrenal CART IR neuronal elements were also VIP IR. CART IR was also seen in a substantial proportion of the C-cells in the thyroid gland. The majority of these cells were also somatostatin IR, and/or 5-HT IR, and/or VIP IR.</p> <p>Conclusion</p> <p>CART is a major neuropeptide in intrinsic neurons of the porcine GI-tract and pancreas, a major constituent of adrenaline producing adrenomedullary cells, and a novel peptide of the thyroid C-cells. CART is suggested to be a regulatory peptide in the porcine pancreas, GI-tract, adrenal gland and thyroid.</p

B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure.

OBJECTIVE: To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi-IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0-9) and of CD20+ B cell infiltrate (on a scale of 0-4). B cell scores were validated by digital image analysis and B cell lineage-specific transcript analysis (RNA-Seq) in the early RA (n = 91) and TNFi-IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2). RESULTS: Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi-IR cohort (P = 0.025). B cell-rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti-citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts. CONCLUSION: We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell-rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA

Post hoc immunostaining of GABAergic neuronal subtypes following in vivo two-photon calcium imaging in mouse neocortex

GABAergic neurons in the neocortex are diverse with regard to morphology, physiology, and axonal targeting pattern, indicating functional specializations within the cortical microcircuitry. Little information is available, however, about functional properties of distinct subtypes of GABAergic neurons in the intact brain. Here, we combined in vivo two-photon calcium imaging in supragranular layers of the mouse neocortex with post hoc immunohistochemistry against the three calcium-binding proteins parvalbumin, calretinin, and calbindin in order to assign subtype marker profiles to neuronal activity. Following coronal sectioning of fixed brains, we matched cells in corresponding volumes of image stacks acquired in vivo and in fixed brain slices. In GAD67-GFP mice, more than 95% of the GABAergic cells could be unambiguously matched, even in large volumes comprising more than a thousand interneurons. Triple immunostaining revealed a depth-dependent distribution of interneuron subtypes with increasing abundance of PV-positive neurons with depth. Most importantly, the triple-labeling approach was compatible with previous in vivo calcium imaging following bulk loading of Oregon Green 488 BAPTA-1, which allowed us to classify spontaneous calcium transients recorded in vivo according to the neurochemically defined GABAergic subtypes. Moreover, we demonstrate that post hoc immunostaining can also be applied to wild-type mice expressing the genetically encoded calcium indicator Yellow Cameleon 3.60 in cortical neurons. Our approach is a general and flexible method to distinguish GABAergic subtypes in cell populations previously imaged in the living animal. It should thus facilitate dissecting the functional roles of these subtypes in neural circuitry

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials

Background: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. Methods: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)–European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). Findings: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47–2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). Interpretation: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. Funding: UK Medical Research Council and Versus Arthritis