OTP-PRL: an app for occupational risk prevention in policing activities

Background: The rapid progress in information and communication technologies has promoted the development of smartphone applications (apps) for a wide variety of purposes including workplace safety. However, no specific apps for occupational risk prevention in the police domain seemingly exist as yet. In this work, an app running under the iOS and Android operating systems was developed to help police officers become acquainted with policing-related occupational risks and to prevent their damaging consequences. Results: The proposed app, which uses an iterative user-centered design to avoid occupational risks in policing activities, was assessed for performance by a group of users and experts through a System Usability Scale (SUS) questionnaire. The mean overall score for the questionnaire was 82.3. The app has backend support to facilitate continual improvement through contributions from users and administrators. A field test revealed increased awareness of policing occupational risks after using the app in many users. Conclusions: A novel product that covers the needs of ORP requirements of police officers has been developed

A Legal and Forensic Medicine Approach to Police Physical Intervention Techniques in High-Risk Situations

Background: The physical intervention techniques (PITs) typically used by the police in troublesome situations are examined in terms of injuring potential depending on whether they target a body zone of high, medium or low vulnerability. Based on legal and forensic considerations, and principles of congruence, opportunity and proportionality, a need exists to favor opponent locking and arrest techniques targeting non-vulnerable zones to minimize the risk of severe damage. Methods: A search of the training manuals for the different kind of law of enforcement officers was carried out. Revision of injuries was available from electronic databases of academic o medical journals. Results: Three different locking and arrest PITs based on operational tactical procedures (OTP) that avoid zones of high or medium vulnerability are proposed. The new techniques use blocking, diverting and grabbing of the upper and lower limbs, followed by dislocation and locking of the same targets. Conclusions: The damaging potential of such PITs was assessed in terms of anatomical region and most were found to have a high risk of severe damage. The alternative PITs proposed here, which rely on OTP, improve in legal and forensic medical terms on existing choices and dramatically reduce the risk of injuring arrestees

Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes

Currently, biased agonism is at the center stage of drug development approaches. We analyzed effects of a battery of cannabinoids plus/minus cannabidiol (CBD) in four functional parameters (cAMP levels, phosphorylation of extracellular signal–regulated kinases (ERK1/2), β-arrestin recruitment and label-free/DMR) in HEK-293T cells expressing cannabinoid receptors, CB or CB, or CB-CB heteroreceptor complexes. In all cases two natural agonists plus two selective synthetic agonists were used. Furthermore, the effect of cannabidiol, at a dose (100 nM) that does not allow significant binding to the orthosteric center of either receptor, was measured. From the huge amount of generated data, we would like to highlight that the two psychotropic molecules (Δ-tetrahydrocannabinol/THC and CP-55940) showed similar bias in CBR and that the bias of THC was particularly relevant toward MAPK pathway. Furthermore, THC did not activate the G protein coupled to CBR. Interestingly, the biased agonism was reduced when assays were performed in cells expressing the two receptors, thus suggesting that the heteromer allows less functional selectivity. In terms of cannabidiol action, the phytocannabinoid altered the functional responses, likely by allosteric means, and modified potency, agonist IC/EC values and biased agonism in qualitative and/or quantitative different ways depending on the agonist. The effect of cannabidiol on anandamide actions on both cannabinoid receptors was particularly noteworthy as was significantly different from that of other compounds. Results are a compendium of data on biased agonism on cannabinoid receptors in the absence and presence of cannabidiol. In addition, for the first time, GPCR biased agonism is characterized in an heteromeric context.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (Ref. no. BFU2015-64405-R and SAF2017-84117-R; they may include FEDER funds) and by grant 201413-30 from: Fundació la Marató de TV3Peer Reviewe

Next-to-leading and resummed BFKL evolution with saturation boundary

We investigate the effects of the saturation boundary on small-x evolution at the next-to-leading order accuracy and beyond. We demonstrate that the instabilities of the next-to-leading order BFKL evolution are not cured by the presence of the nonlinear saturation effects, and a resummation of the higher order corrections is therefore needed for the nonlinear evolution. The renormalization group improved resummed equation in the presence of the saturation boundary is investigated, and the corresponding saturation scale is extracted. A significant reduction of the saturation scale is found, and we observe that the onset of the saturation corrections is delayed to higher rapidities. This seems to be related to the characteristic feature of the resummed splitting function which at moderately small values of x possesses a minimum.Comment: 34 page

Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

Objectives: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. Methods: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score = 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. Results: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. Conclusions: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal

She\u27s So Bubbly

We introduce the Automatic Learning for the Rapid Classification of Events (ALeRCE) broker, an astronomical alert broker designed to provide a rapid and self-consistent classification of large etendue telescope alert streams, such as that provided by the Zwicky Transient Facility (ZTF) and, in the future, the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). ALeRCE is a Chilean-led broker run by an interdisciplinary team of astronomers and engineers working to become intermediaries between survey and follow-up facilities. ALeRCE uses a pipeline that includes the real-time ingestion, aggregation, cross-matching, machine-learning (ML) classification, and visualization of the ZTF alert stream. We use two classifiers: a stamp-based classifier, designed for rapid classification, and a light curve–based classifier, which uses the multiband flux evolution to achieve a more refined classification. We describe in detail our pipeline, data products, tools, and services, which are made public for the community (see https://alerce.science). Since we began operating our real-time ML classification of the ZTF alert stream in early 2019, we have grown a large community of active users around the globe. We describe our results to date, including the real-time processing of 1.5 × 10⁸ alerts, the stamp classification of 3.4 × 10⁷ objects, the light-curve classification of 1.1 × 10⁶ objects, the report of 6162 supernova candidates, and different experiments using LSST-like alert streams. Finally, we discuss the challenges ahead in going from a single stream of alerts such as ZTF to a multistream ecosystem dominated by LSST

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Unraveling the Nanoscopic Organization and Function of Central Mammalian Presynapses With Super-Resolution Microscopy

The complex, nanoscopic scale of neuronal function, taking place at dendritic spines, axon terminals, and other minuscule structures, cannot be adequately resolved using standard, diffraction-limited imaging techniques. The last couple of decades saw a rapid evolution of imaging methods that overcome the diffraction limit imposed by Abbe's principle. These techniques, including structured illumination microscopy (SIM), stimulated emission depletion (STED), photo-activated localization microscopy (PALM), and stochastic optical reconstruction microscopy (STORM), among others, have revolutionized our understanding of synapse biology. By exploiting the stochastic nature of fluorophore light/dark states or non-linearities in the interaction of fluorophores with light, by using modified illumination strategies that limit the excitation area, these methods can achieve spatial resolutions down to just a few tens of nm or less. Here, we review how these advanced imaging techniques have contributed to unprecedented insight into the nanoscopic organization and function of mammalian neuronal presynapses, revealing new organizational principles or lending support to existing views, while raising many important new questions. We further discuss recent technical refinements and newly developed tools that will continue to expand our ability to delve deeper into how synaptic function is orchestrated at the nanoscopic level