Learning the signatures of the human grasp using a scalable tactile glove.

Humans can feel, weigh and grasp diverse objects, and simultaneously infer their material properties while applying the right amount of force-a challenging set of tasks for a modern robot1. Mechanoreceptor networks that provide sensory feedback and enable the dexterity of the human grasp2 remain difficult to replicate in robots. Whereas computer-vision-based robot grasping strategies3-5 have progressed substantially with the abundance of visual data and emerging machine-learning tools, there are as yet no equivalent sensing platforms and large-scale datasets with which to probe the use of the tactile information that humans rely on when grasping objects. Studying the mechanics of how humans grasp objects will complement vision-based robotic object handling. Importantly, the inability to record and analyse tactile signals currently limits our understanding of the role of tactile information in the human grasp itself-for example, how tactile maps are used to identify objects and infer their properties is unknown6. Here we use a scalable tactile glove and deep convolutional neural networks to show that sensors uniformly distributed over the hand can be used to identify individual objects, estimate their weight and explore the typical tactile patterns that emerge while grasping objects. The sensor array (548 sensors) is assembled on a knitted glove, and consists of a piezoresistive film connected by a network of conductive thread electrodes that are passively probed. Using a low-cost (about US$10) scalable tactile glove sensor array, we record a large-scale tactile dataset with 135,000 frames, each covering the full hand, while interacting with 26 different objects. This set of interactions with different objects reveals the key correspondences between different regions of a human hand while it is manipulating objects. Insights from the tactile signatures of the human grasp-through the lens of an artificial analogue of the natural mechanoreceptor network-can thus aid the future design of prosthetics7, robot grasping tools and human-robot interactions1,8-10.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Understanding the role of individual units in a deep neural network.

Deep neural networks excel at finding hierarchical representations that solve complex tasks over large datasets. How can we humans understand these learned representations? In this work, we present network dissection, an analytic framework to systematically identify the semantics of individual hidden units within image classification and image generation networks. First, we analyze a convolutional neural network (CNN) trained on scene classification and discover units that match a diverse set of object concepts. We find evidence that the network has learned many object classes that play crucial roles in classifying scene classes. Second, we use a similar analytic method to analyze a generative adversarial network (GAN) model trained to generate scenes. By analyzing changes made when small sets of units are activated or deactivated, we find that objects can be added and removed from the output scenes while adapting to the context. Finally, we apply our analytic framework to understanding adversarial attacks and to semantic image editing.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis.

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Model of a Device-Level Combined Wireless Network Based on NB-IoT and IEEE 802.15.4 Standards for Low-Power Applications in a Diverse IoT Framework.

With the development of the Internet of Things (IoT), Low Data Rate-Personal Area Networks (LR-WPAN) have been deployed for different applications. Now comes the need to integrate these networks in search of greater connectivity, performances, and geographic coverage. This integration is facilitated by the recent deployment of low power wide area networks (LPWAN) in the licensed bands, especially narrowband IoT (NB-IoT) and long-term evolution for machine-type communications (LTE-M), which are standardized technologies that will continue evolving as part of the fifth generation (5G) specifications. This paper proposes a design methodology for combined networks using LR-WPAN and LPWAN technologies. These networks are combined at the device level using a cluster-tree topology. An example is shown here, where an existing IEEE 802.15.4 network is combined with NB-IoT. To this end, new dual nodes are incorporated, acting as cluster heads. The paper discusses the different aspects of formation and operation of the combined network. A dynamic link selection (DLS) algorithm is also proposed, based on which cluster headers dynamically determine the preferred link, depending on link quality and type of traffic. Extensive simulations show that the DLS algorithm significantly increases battery life on dual nodes, which are the nodes with the highest power demands.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Chaotic oscillations, dissipation and mirror symmetry breaking in a chiral catalytic network.

Catalytic reaction networks consist of molecular arrays interconnected by autocatalysis and cross-catalytic pathways among the reactants, and serve as bottom-up models for the design and understanding of molecular evolution and emergent phenomena. An important example of the latter is the emergence of homochirality in biomolecules during chemical evolution. This chiral symmetry breaking is triggered by bistability and bifurcation in networks of chiral replicators. Spontaneous mirror symmetry breaking (SMSB) results from hypercyclic connectivity when the chirality and enantioselectivity of the replicators are taken into account. Heretofore, SMSB has been generally understood as involving chemical transformations yielding scalemic outcomes as non-equilibrium steady states (NESS). Here, in marked contrast, we consider the chaotic regime, in which steady states do not exist. The dissipation, or entropy production, is chaotic as is the exchange entropy. The rate of change of the total system entropy, governed by the entropy balance equation, is also chaotic. Subsequent to the mirror symmetry breaking transition, the time averaged entropy production is minimized in the final chaotic chiral state with respect to the former chaotic racemic state. The chemical forces (i.e., the affinities) evolve in time so as to lower the sum of the entropy production and the exchange entropy, in compliance with the general evolution criterion extended to reaction networks subject to volumetric open flow.

A prospective multicenter study assessing effectiveness and safety of secukinumab in a real-life setting in 158 patients.

BACKGROUND: Secukinumab is a first-in-class interleukin 17A monoclonal antibody that has demonstrated an excellent safety and efficacy profile in phase 3 studies. OBJECTIVE: To evaluate the effectiveness of secukinumab in daily clinical practice and to understand the clinical and epidemiologic characteristics of patients treated with secukinumab in clinical settings. METHODS: In this multicenter prospective observational study, we recruited adult patients with moderate-to-severe plaque psoriasis from 12 hospitals in Spain during January-December 2016. These patients were treated with secukinumab and prospectively followed at 12-week intervals for 52 weeks. RESULTS: In total, 158 patients were recruited to the study. A Psoriasis Area and Severity Index (PASI) score improvement ≥75% over baseline (PASI-75) was achieved by 57%, 83.5%, 89%, and 78.5% of patients at weeks 4, 12, 24, and 52, respectively. PASI-90 was achieved in 27.8%, 62%, 64.6%, and 63.2% of patients at weeks 4, 12, 24, and 52, respectively; PASI-75 and PASI-90 responders were significantly more common among patients with a body mass index <30 kg/cm2 and patients without previous biologic therapy failures. LIMITATIONS: Observational study. Time from onset of psoriasis was not evaluated. CONCLUSION: Secukinumab is a safe treatment with effectiveness rates similar to those found in its phase 3 studies. These rates endure up to a year from start of treatment.

ITERL: A Wireless Adaptive System for Efficient Road Lighting.

This work presents the development and construction of an adaptive street lighting system that improves safety at intersections, which is the result of applying low-power Internet of Things (IoT) techniques to intelligent transportation systems. A set of wireless sensor nodes using the Institute of Electrical and Electronics Engineers (IEEE) 802.15.4 standard with additional internet protocol (IP) connectivity measures both ambient conditions and vehicle transit. These measurements are sent to a coordinator node that collects and passes them to a local controller, which then makes decisions leading to the streetlight being turned on and its illumination level controlled. Streetlights are autonomous, powered by photovoltaic energy, and wirelessly connected, achieving a high degree of energy efficiency. Relevant data are also sent to the highway conservation center, allowing it to maintain up-to-date information for the system, enabling preventive maintenance.

Revealing hidden scenes by photon-efficient occlusion-based opportunistic active imaging.

The ability to see around corners, i.e., recover details of a hidden scene from its reflections in the surrounding environment, is of considerable interest in a wide range of applications. However, the diffuse nature of light reflected from typical surfaces leads to mixing of spatial information in the collected light, precluding useful scene reconstruction. Here, we employ a computational imaging technique that opportunistically exploits the presence of occluding objects, which obstruct probe-light propagation in the hidden scene, to undo the mixing and greatly improve scene recovery. Importantly, our technique obviates the need for the ultrafast time-of-flight measurements employed by most previous approaches to hidden-scene imaging. Moreover, it does so in a photon-efficient manner (i.e., it only requires a small number of photon detections) based on an accurate forward model and a computational algorithm that, together, respect the physics of three-bounce light propagation and single-photon detection. Using our methodology, we demonstrate reconstruction of hidden-surface reflectivity patterns in a meter-scale environment from non-time-resolved measurements. Ultimately, our technique represents an instance of a rich and promising new imaging modality with important potential implications for imaging science.