Independent Configurable Architecture for Reliable Operation of Unmanned Systems with Distributed Onboard Services

This paper presents the development of ICAROUS-2 (Independent Configurable Architecture for Reliable Operation of Unmanned Systems with Distributed Onboard Services), the second generation of a software architecture that integrates several algorithms as distributed onboard services to enable robust autonomous UAS applications. In particular, the ICAROUS architecture defines a framework to perform detect and avoid, geofencing, path monitoring, path planning, and autonomous decision making to ensure safety and mission progress. Most of the core algorithms implemented in ICAROUS are formally verified using an interactive theorem prover. These algorithms are composed together using a plan execution engine, whose operational semantics is formally specified. A description of the integrated architecture, services currently available, and flight test results highlighting the capability of ICAROUS are presented

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition

Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases

212 Phase 2, randomized, double-blind, placebo-controlled, dose-finding study, evaluating the Bruton's tyrosine kinase inhibitor evobrutinib in patients with systemic lupus erythematosus: study design

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Difference in clinical profile between juvenile onset and adult-onset systemic lupus erythematosus: a meta-analysis

The aim was to systematically review the studies that compared clinical and serological variation between adult-onset systematic lupus erythematosus (aSLE) andjuvenile-onset systematic lupus erythematosus (jSLE). A comprehensive literature search was done, in various available electronic databases for relevant publication that compared juvenile onset SLE and adult onset SLE. The data of adverse clinical features, serological profile and mortality were extracted. Juvenile onset was defined as 18 years. The methodological quality of study was assessed by Newcastle Ottawa scale (NOS) criteria and R version 3.3.1 was used for analysis and ORs and 95% CIs, were used as statistical parameter. A total of 14,920 patients; (12,230: aSLE, and 2,690: jSLE) were included. Renal involvement especially nephritis was significantly more in j-SLE OR: 2.18, 95% CI: [1.81;2.62]; I2=10.8% whereas musculoskeletal was significant in aSLE O.R: 0.64; C.I: [0.44; 0.93]; I2=83.4%. Seizure and malar rash were significantly higher in J-SLE OR:1.69, CI: [1.31; 2.18]; I2=31.1%,1.43; C.I [1.04; 1.97]; I2=82%, respectively. Raynaud’s phenomenon and pleuritis were significantly higher in adult onset SLE. Anemia and thrombocytopenia were significantly higher in juvenile onset SLE. Anti-ds DNA, anti-histone, and anti-ribosomal-P were more frequent in juvenile-onset SLE while, anti-Ro was more common in adult-onset disease. The cause of mortality was not significantly different in both groups. Renal biopsy of class III and IV combined and class V were significantly more in adult-onset SLE. SLEDAI was higher in j-SLE. Meta-analysis indicated that, regardless of many similar clinical and serological manifestations, there is still some variation between adult-onset SLE and juvenile-onset SLE. Although, SLE disease is continuum from juvenile to adult but disease aggressive in juvenile onset SLE

215 First-in-man study evaluating the safety, tolerability, pharmacokinetics and concentrationQT analysis of the novel BTK inhibitor evobrutinib (M2951) in healthy volunteers

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The Healthy Activity Program lay counsellor delivered treatment for severe depression in India: systematic development and randomised evaluation

BACKGROUND: Reducing the global treatment gap for mental disorders requires treatments that are economical, effective and culturally appropriate. AIMS: To describe a systematic approach to the development of a brief psychological treatment for patients with severe depression delivered by lay counsellors in primary healthcare. METHOD: The treatment was developed in three stages using a variety of methods: (a) identifying potential strategies; (b) developing a theoretical framework; and (c) evaluating the acceptability, feasibility and effectiveness of the psychological treatment. RESULTS: The Healthy Activity Program (HAP) is delivered over 6-8 sessions and consists of behavioral activation as the core psychological framework with added emphasis on strategies such as problem-solving and activation of social networks. Key elements to improve acceptability and feasibility are also included. In an intention-to-treat analysis of a pilot randomised controlled trial (55 participants), the prevalence of depression (Beck Depression Inventory II ⩾19) after 2 months was lower in the HAP than the control arm (adjusted risk ratio = 0.55, 95% CI 0.32-0.94,P= 0.01). CONCLUSIONS: Our systematic approach to the development of psychological treatments could be extended to other mental disorders. HAP is an acceptable and effective brief psychological treatment for severe depression delivered by lay counsellors in primary care

Reflections on a Post-COVID World: Lessons from the Surge.

This conversation was held on June 16, 2020, and the resulting transcript reflects the events that were current as of the time of the original discussion. Changes to policies, events, and data may have changed between the time of the discussion and its publication

Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals

Epithelial hyperplasia and metaplasia are common features of inflammatory and neoplastic disease, but the basis for the altered epithelial phenotype is often uncertain. Here we show that long-term ciliated cell hyperplasia coincides with mucous (goblet) cell metaplasia after respiratory viral clearance in mouse airways. This chronic switch in epithelial behavior exhibits genetic susceptibility and depends on persistent activation of EGFR signaling to PI3K that prevents apoptosis of ciliated cells and on IL-13 signaling that promotes transdifferentiation of ciliated to goblet cells. Thus, EGFR blockade (using an irreversible EGFR kinase inhibitor designated EKB-569) prevents virus-induced increases in ciliated and goblet cells whereas IL-13 blockade (using s-IL-13Rα2-Fc) exacerbates ciliated cell hyperplasia but still inhibits goblet cell metaplasia. The distinct effects of EGFR and IL-13 inhibitors after viral reprogramming suggest that these combined therapeutic strategies may also correct epithelial architecture in the setting of airway inflammatory disorders characterized by a similar pattern of chronic EGFR activation, IL-13 expression, and ciliated-to-goblet cell metaplasia

The Peculiar Debris Disk of HD 111520 as Resolved by the Gemini Planet Imager

Using the Gemini Planet Imager (GPI), we have resolved the circumstellar debris disk around HD 111520 at a projected range of ~30-100 AU in both total and polarized $H$-band intensity. The disk is seen edge-on at a position angle of ~165$^{\circ}$ along the spine of emission. A slight inclination or asymmetric warping are covariant and alters the interpretation of the observed disk emission. We employ 3 point spread function (PSF) subtraction methods to reduce the stellar glare and instrumental artifacts to confirm that there is a roughly 2:1 brightness asymmetry between the NW and SE extension. This specific feature makes HD 111520 the most extreme examples of asymmetric debris disks observed in scattered light among similar highly inclined systems, such as HD 15115 and HD 106906. We further identify a tentative localized brightness enhancement and scale height enhancement associated with the disk at ~40 AU away from the star on the SE extension. We also find that the fractional polarization rises from 10 to 40% from 0.5" to 0.8" from the star. The combination of large brightness asymmetry and symmetric polarization fraction leads us to believe that an azimuthal dust density variation is causing the observed asymmetry.Comment: 9 pages, 8 Figures, 1 table, Accepted to Ap

How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221]

BACKGROUND: Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop(®), Smith-Nephew) provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC) remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW) infants during insertion of a PICC. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP). A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58). Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117). Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group). No serious harms were observed. CONCLUSION: Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants