UniDetector: Towards Universal Object Detection with Heterogeneous Supervision.

In this paper, we formally address universal object detection, which aims to detect every category in every scene. The dependence on human annotations, the limited visual information, and the novel categories in open world severely restrict the universality of detectors. We propose UniDetector, a universal object detector that recognizes enormous categories in the open world. The critical points for UniDetector are: 1) it leverages images of multiple sources and heterogeneous label spaces in training through image-text alignment, which guarantees sufficient information for universal representations. 2) it involves heterogeneous supervision training, which alleviates the dependence on the limited fully-labeled images. 3) it generalizes to open world easily while keeping the balance between seen and unseen classes. 4) it further promotes generalizing to novel categories through our proposed decoupling training manner and probability calibration. These contributions allow UniDetector to detect over 7k categories, the largest measurable size so far, with only about 500 classes participating in training. Our UniDetector behaves the strong zero-shot ability on large-vocabulary datasets - it surpasses supervised baselines by more than 5% without seeing any corresponding images. On 13 detection datasets with various scenes, UniDetector also achieves state-of-the-art performance with only a 3% amount of training data.

Certolizumab pegol effectiveness, survival and safety in patients with psoriasis: A multicenter retrospective analysis in daily clinical practice by the Spanish Psoriasis Group.

BACKGROUND: Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions. METHODS: This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting. RESULTS: A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn. CONCLUSIONS: Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice.

Contextual and combinatorial structure in sperm whale vocalisations.

Sperm whales (Physeter macrocephalus) are highly social mammals that communicate using sequences of clicks called codas. While a subset of codas have been shown to encode information about caller identity, almost everything else about the sperm whale communication system, including its structure and information-carrying capacity, remains unknown. We show that codas exhibit contextual and combinatorial structure. First, we report previously undescribed features of codas that are sensitive to the conversational context in which they occur, and systematically controlled and imitated across whales. We call these rubato and ornamentation. Second, we show that codas form a combinatorial coding system in which rubato and ornamentation combine with two context-independent features we call rhythm and tempo to produce a large inventory of distinguishable codas. Sperm whale vocalisations are more expressive and structured than previously believed, and built from a repertoire comprising nearly an order of magnitude more distinguishable codas. These results show context-sensitive and combinatorial vocalisation can appear in organisms with divergent evolutionary lineage and vocal apparatus.

Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.

Adaptive tactile interaction transfer via digitally embroidered smart gloves.

Human-machine interfaces for capturing, conveying, and sharing tactile information across time and space hold immense potential for healthcare, augmented and virtual reality, human-robot collaboration, and skill development. To realize this potential, such interfaces should be wearable, unobtrusive, and scalable regarding both resolution and body coverage. Taking a step towards this vision, we present a textile-based wearable human-machine interface with integrated tactile sensors and vibrotactile haptic actuators that are digitally designed and rapidly fabricated. We leverage a digital embroidery machine to seamlessly embed piezoresistive force sensors and arrays of vibrotactile actuators into textiles in a customizable, scalable, and modular manner. We use this process to create gloves that can record, reproduce, and transfer tactile interactions. User studies investigate how people perceive the sensations reproduced by our gloves with integrated vibrotactile haptic actuators. To improve the effectiveness of tactile interaction transfer, we develop a machine-learning pipeline that adaptively models how each individual user reacts to haptic sensations and then optimizes haptic feedback parameters. Our interface showcases adaptive tactile interaction transfer through the implementation of three end-to-end systems: alleviating tactile occlusion, guiding people to perform physical skills, and enabling responsive robot teleoperation.

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.

Drug survival and safety of biosimilars and originator adalimumab in the treatment of psoriasis: a multinational cohort study.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage. METHODS AND ANALYSIS: This study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes. ETHICS AND DISSEMINATION: The participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.

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.

Incidents1M: A Large-Scale Dataset of Images With Natural Disasters, Damage, and Incidents.

Natural disasters, such as floods, tornadoes, or wildfires, are increasingly pervasive as the Earth undergoes global warming. It is difficult to predict when and where an incident will occur, so timely emergency response is critical to saving the lives of those endangered by destructive events. Fortunately, technology can play a role in these situations. Social media posts can be used as a low-latency data source to understand the progression and aftermath of a disaster, yet parsing this data is tedious without automated methods. Prior work has mostly focused on text-based filtering, yet image and video-based filtering remains largely unexplored. In this work, we present the Incidents1M Dataset, a large-scale multi-label dataset which contains 977,088 images, with 43 incident and 49 place categories. We provide details of the dataset construction, statistics and potential biases; introduce and train a model for incident detection; and perform image-filtering experiments on millions of images on Flickr and Twitter. We also present some applications on incident analysis to encourage and enable future work in computer vision for humanitarian aid. Code, data, and models are available at http://incidentsdataset.csail.mit.edu.

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).

CNVs Associated with Different Clinical Phenotypes of Psoriasis and Anti-TNF-Induced Palmoplantar Pustulosis.

BACKGROUND: Psoriasis can present different phenotypes and could affect diverse body areas. In contrast to the high effectiveness of biological drugs in the treatment of trunk and extremities plaque psoriasis, in palmoplantar phenotypes and in plaque scalp psoriasis, these same drugs usually have reduced efficacy. Anti-TNF drugs could induce the appearance of palmoplantar pustulosis (PPP) in patients with other inflammatory diseases. The objective of this study is to identify if there are DNA Copy Number Variations (CNVs) associated with these different clinical phenotypes, which could justify the differences found in clinical practice. Moreover, we intend to elucidate if anti-TNF-induced PPP has a similar genetic background to idiopathic PPP. METHODS: Skin samples were collected from 39 patients with different patterns of psoriasis and six patients with anti-TNF-induced PPP. The CNVs were obtained from methylation array data (Illumina Infinium Human Methylation) using the conumee R package. RESULTS: No significant CNVs were found between the different phenotypes and the locations of psoriasis compared. Nevertheless, we found two significant bins harboring five different genes associated with anti-TNF-induced PPP in patients with a different background other than psoriasis. CONCLUSIONS: Our results may help to predict which patients could develop anti-TNF-induced PPP.

Toward understanding the communication in sperm whales.

Machine learning has been advancing dramatically over the past decade. Most strides are human-based applications due to the availability of large-scale datasets; however, opportunities are ripe to apply this technology to more deeply understand non-human communication. We detail a scientific roadmap for advancing the understanding of communication of whales that can be built further upon as a template to decipher other forms of animal and non-human communication. Sperm whales, with their highly developed neuroanatomical features, cognitive abilities, social structures, and discrete click-based encoding make for an excellent model for advanced tools that can be applied to other animals in the future. We outline the key elements required for the collection and processing of massive datasets, detecting basic communication units and language-like higher-level structures, and validating models through interactive playback experiments. The technological capabilities developed by such an undertaking hold potential for cross-applications in broader communities investigating non-human communication and behavioral research.

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.

Current state, control, impact and management of rheumatoid arthritis according to patient: AR 2020 national survey.

OBJECTIVES: To analyse current status, control and impact of RA on patients' lives as well as the management of RA symptoms. METHODS: A structured anonymous online questionnaire was designed and sent to patients with RA, aged 18 years or above living in Spain. Participants were invited though different strategies: 1) ConArtritis and related patients associations; 2) Patients participating in the platform www.in-pacient.es; 3) Links from ConArtritis website and open social networks. Sociodemographic and clinical variables, as well as others related to the objectives were collected. A descriptive analysis was performed. RESULTS: We analysed 882 RA patients, 89% women, with a median age of 52 years, 31.9% disease duration <5 years. They reported a mean pain and patient global disease score (0-10) of 5.1 and 4.9 respectively. The rate of patients with many difficulties or inability to perform daily tasks varied from 6.4% to 49.2%. Based on the activity index 56.8% of patients reported high activity. We found a great or severe impact on the emotional well-being in 31.5% of patients, and of 29.2% in the workplace or academic setting. A total of 87.9% are taking some medication for RA, and 17.3% are little/not satisfied with them. In addition, 67.1% take conventional synthetic disease modifying drugs (DMARDs), and 45.9% biological therapies including biosimilars and small molecules. CONCLUSIONS: The current impact of RA on patients' daily lives remains very high. A significant number of patients are not taking DMARDs (conventional synthetic and/or biologics) despite high activity.

Estado, control, impacto y manejo actual de la artritis reumatoide según los pacientes: encuesta nacional AR 2020 / Current State, Control, Impact and Management of Rheumatoid Arthritis According to Patient: AR 2020 National Survey

Objetivos: Analizar el estado, el control, el impacto y el manejo actual de la artritis reumatoide (AR) según los pacientes. Métodos: Encuesta para la que se envió un cuestionario estructurado, anónimo, en formato electrónico a pacientes adultos con AR residentes en España, a través de: 1) Con Artritis o sus asociaciones; 2) pacientes de la plataforma www.in-pacient.es, y 3) vínculos desde la página web de Con Artritis y redes sociales abiertas. Se recogieron variables sociodemográficas y clínicas, y otras relacionadas con los objetivos propuestos. Se realizó un análisis descriptivo. Resultados: Analizamos a 882 pacientes, 89% mujeres, con una edad mediana de 52 años, 31,9% AR <5 años de evolución. El dolor y la valoración global de la enfermedad actuales medios (0-10) fueron de 5,1 y 4,9, respectivamente. El porcentaje de pacientes con muchas dificultades o imposibilidad para realizar tareas cotidianas varió del 6,4 al 49,2%. Con base en el índice de actividad, el 56,8% de los pacientes presenta alta actividad. Los pacientes refieren mucho impacto o impacto grave del 31,5% a nivel emocional, o del 29,2% en el ámbito laboral o académico. El 87,9% sigue algún tratamiento para la AR y el 17,3% está poco/nada satisfecho con el mismo. El 67,1% toma fármacos modificadores de la enfermedad (FAME) sintéticos convencionales y el 45,9%, terapias biológicas incluyendo biosimilares y pequeñas moléculas. Conclusiones: El impacto actual de la AR en la vida del paciente sigue siendo muy alto. Un porcentaje significativo de pacientes no sigue un tratamiento con FAME (sintéticos convencionales o biológicos) a pesar de su actividad.(AU)

Objectives: To analyse current status, control and impact of RA on patients’ lives as well as the management of RA symptoms. Methods: A structured anonymous online questionnaire was designed and sent to patients with RA, aged 18 years or above living in Spain. Participants were invited though different strategies: 1) ConArtritis and related patients associations; 2) Patients participating in the platform www.in-pacient.es; 3) Links from ConArtritis website and open social networks. Sociodemographic and clinical variables, as well as others related to the objectives were collected. A descriptive analysis was performed. Results: We analysed 882 RA patients, 89% women, with a median age of 52 years, 31.9% disease duration <5 years. They reported a mean pain and patient global disease score (0-10) of 5.1 and 4.9 respectively. The rate of patients with many difficulties or inability to perform daily tasks varied from 6.4% to 49.2%. Based on the activity index 56.8% of patients reported high activity. We found a great or severe impact on the emotional well-being in 31.5% of patients, and of 29.2% in the workplace or academic setting. A total of 87.9% are taking some medication for RA, and 17.3% are little / not satisfied with them. In addition, 67.1% take conventional synthetic disease modifying drugs (DMARDs), and 45.9% biological therapies including biosimilars and small molecules. Conclusions: The current impact of RA on patients’ daily lives remains very high. A significant number of patients are not taking DMARDs (conventional synthetic and / or biologics) despite high activity.(AU)