Добірка наукової літератури з теми "Leo A. Daly Company"

The article substantiates the necessity to expand research methodologies into the electronic newsletter format. It was acknowledged that modern scientific discourse reluctantly chooses the electronic bulletin as an object of research. At the same time, scholars concur with the fact that this format demonstrates potential while being a user-friendly channel of communicative interaction as well as providing an opportunity to create personalised communication and offer exclusive content, etc. The article examines the examples of the most sought-after newsletters such as: editorial newsletters from The New York Times, aggregated newsletters from SmartBrief, Think with Google resource, The Menu newsletter from SparkToro technical startup, Confident Computing's latest technology newsletter from Ask Leo! website and the female-focused Daily Skimm newsletter from theSkimm media company. The specifics, characteristics, and advantages of this form of interaction with the audience are analysed. It is concluded that tailored personalised content that the user receives via e-mail allows the company to effectively communicate, interact with its target audiences, increasing the level of engagement, building trust and upholding reputation. In this case, the indicators of the website opening, clickability and conversion, make it possible to improve the strategy of email distributions, which will ensure better results. The electronic newsletter is a modern, up-to-date format which helps to perform effective multi-functional social communication, provided it contains interesting, high-quality, interactive, scheduled content aimed at the target audience.

BackgroundTyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signalling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective TYK2 inhibitor that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA.1 The efficacy and tolerability of deucravacitinib in patients with moderate to severe psoriasis were previously demonstrated in 2 pivotal, Phase 3, double-blind trials, POETYK PSO-1 and PSO-2.2ObjectivesTo assess the long-term efficacy and safety of deucravacitinib in patients with psoriasis in a Phase 3, open-label, long-term extension (LTE) trial.MethodsThe 52-week PSO-1 and PSO-2 trials randomised patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients could then enrol in the LTE trial and receive open-label deucravacitinib 6 mg once daily.Results1221 patients enrolled in the LTE trial and received ≥1 dose of deucravacitinib. Demographic and baseline disease characteristics were balanced across treatment groups; mean age at disease onset was 28.6 years, mean disease duration was 18.9 years, and 18.0% of patients had PsA at baseline. Cumulative exposures in person-years from randomisation in PSO-1 or PSO-2 and the LTE trial were 2166.9 and 2482.0 for efficacy and safety analyses, respectively. At enrolment in the LTE trial, PASI 75 and sPGA 0/1 response rates were 65.1% and 50.9%, respectively, and were maintained for up to 2 years after initial randomisation (Week 48 of LTE; PASI 75: 75.7%; sPGA 0/1: 56.4% [as observed]). Exposure-adjusted incidence rates per 100 person-years for adverse events were similar in the controlled period (Weeks 0–52) of PSO-1 and PSO-2 and during the cumulative PSO-1, PSO-2, and LTE trial period (229.2 [controlled period] vs 154.4 [cumulative period]), serious adverse events (5.7 vs 6.1), discontinuations (4.4 vs 2.8), deaths (0.2 vs 0.4), herpes zoster (0.9 vs 0.7), malignancies (1.0 vs 0.9), major adverse cardiovascular events (0.3 vs 0.4), and venous thromboembolism (0.1 vs 0.1).ConclusionDeucravacitinib demonstrated persistent efficacy and consistent safety profiles in patients with psoriasis for up to 2 years after initial randomisation in the POETYK PSO-1, PSO-2, and LTE trials.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Writing and editorial assistance was provided by Lisa Feder, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, funded by Bristol Myers Squibb.Disclosure of InterestsRichard B. Warren Consultant of: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, UNION, and Xenoport, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, UCB, Howard Sofen Consultant of: Clinical investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma., Shinichi Imafuku Grant/research support from: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Janssen, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin; Personal fees: Amgen (Celgene), Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB, Jacek Szepietowski Consultant of: Advisory board member/consultant: AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; Speaker: AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; Investigator: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, and Trevi, Andrew Blauvelt Consultant of: Scientific adviser and/or clinical study investigator: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Vibliome, Lynda Spelman Consultant of: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck (MSD), Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab, Elizabeth Colston Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Jessica Toms Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alex Buck Employee of: Contractor (through functional service provider Cytel): Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alan Menter Consultant of: Advisory board: Abbott Labs, Amgen, Boehringer Ingelheim, Janssen Biotech, Leo Pharma; consultant: Abbott Labs, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: Abbott Labs, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: Abbott Labs, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates interleukin (IL)-23, IL-12, and interferon (IFN)α/β signaling. Deucravacitinib is a novel, oral, selective inhibitor of TYK2 acting via binding to the TYK2 regulatory domain.1 Phase 2 results showed deucravacitinib was efficacious and well tolerated versus placebo in patients with moderate to severe plaque psoriasis or active psoriatic arthritis.2,3 No herpes zoster infections, opportunistic infections, thromboembolic events, or hematologic or lipid abnormalities characteristic of Janus kinase (JAK) 1−3 inhibitors were reported in the Phase 2 trials.2,3Objectives:To compare the efficacy and safety of deucravacitinib versus placebo and apremilast in plaque psoriasis.Methods:This Phase 3, double-blinded, 52-week study (NCT03624127) randomized patients with moderate to severe plaque psoriasis (BSA ≥10%, PASI ≥12, sPGA ≥3) to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily (2:1:1). Patients receiving placebo were switched to deucravacitinib at Week 16; apremilast-treated patients not achieving PASI 50 at Week 24 were switched to deucravacitinib. Coprimary endpoints were PASI 75 and sPGA 0/1 response versus placebo at Week 16. Key secondary endpoints included superiority versus apremilast, assessed via multiple measures.Results:666 patients were randomized. Demographic and baseline disease characteristics were balanced across groups; mean age was 46.1 years, mean disease duration was 17.3 years, 18.2% of patients had psoriatic arthritis at baseline, and 38.9% had previously used biologic therapy. Mean BSA involvement at baseline was 26.3%, mean PASI was 21.4, and the percentage with severe sPGA (score=4) at baseline was 21.2%. Significantly greater proportions of patients in the deucravacitinib versus placebo and apremilast arms achieved PASI 75 (58.7% vs 12.7% vs 35.1%, respectively; P<0.0001) and sPGA 0/1 (53.6% vs 7.2% vs 32.1%, respectively; P<0.0001) response at Week 16 (Figure 1). Deucravacitinib was also superior to apremilast at Week 24, with 69.0% versus 38.1% of patients achieving PASI 75 and 58.4% versus 31.0% achieving sPGA 0/1 (P<0.0001 for both). In addition, DLQI 0/1 responses at Week 16 were significantly higher with deucravacitinib versus placebo and apremilast, demonstrating improved quality of life (40.7% vs 10.6% vs 28.6%, respectively; Figure 1). During the 16-week, placebo-controlled period, the most common AEs (≥5% in any arm) were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and nausea (Table 1). Frequencies of SAEs and treatment discontinuations due to AEs were low (Table 1).Table 1.Summary of adverse events (AEs) through Week 16Patients, n (%)Deucravacitinibn=332Placebon=165Apremilastn=168Any AEs176 (53.0)70 (42.4)93 (55.4)Severe AEs5 (1.5)7 (4.2)5 (3.0)Serious AEs7 (2.1)9 (5.5)4 (2.4)AEs leading to treatment discontinuation6 (1.8)7 (4.2)10 (6.0)Most common AEs (≥5% in any arm) Nasopharyngitis21 (6.3)7 (4.2)14 (8.3) Upper respiratory tract infection21 (6.3)6 (3.6)3 (1.8) Headache16 (4.8)5 (3.0)17 (10.1) Diarrhea13 (3.9)6 (3.6)17 (10.1) Nausea7 (2.1)4 (2.4)19 (11.3)Conclusion:Deucravacitinib demonstrated superiority versus placebo and apremilast across multiple efficacy endpoints in patients with moderate to severe plaque psoriasis, and was generally well tolerated. Overall, the efficacy and safety profile of deucravacitinib was consistent with that observed in the Phase 2 plaque psoriasis and psoriatic arthritis trials.2,3References:[1]Burke JR et al. Sci Transl Med. 2019;11:1-16.[2]Papp K et al. N Engl J Med. 2018;379:1313-21.[3]Mease PJ et al. Presented at: Annual Scientific Meeting of the American College of Rheumatology; November 5-9, 2020; Virtual meeting.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:April Armstrong Consultant of: Grants and personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis; Personal fees from Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, Valeant, Grant/research support from: Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work; Grants and personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, Melinda Gooderham Shareholder of: Speakers bureau, consultant, investigator/advisor: AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, Sanofi, Xenoport, UCB, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, UCB, Kim Papp Speakers bureau: AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Valeant, Consultant of: Scientific officer/steering committee/advisory board: AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Valeant, Grant/research support from: AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant;Consultant: AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Merck Sharp & Dohme, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; Honoraria: AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Takeda, UCB, Valeant, Bruce Strober Speakers bureau: AbbVie, Janssen, Eli Lilly, Ortho Dermatologics, Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, GSK, Janssen, Kyowa Hakko Kirin, Leo Pharma, Medac, Meiji Seika Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB; Scientific Director (consulting fee): Corrona Psoriasis Registry; Investigator: AbbVie, Corrona Psoriasis Registry, Dermavant, Dermira., Diamant Thaçi Paid instructor for: Lectures: AbbVie, Almirall, Amgen, DS-Pharma, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution, UCB; Scientific advisory board: AbbVie, Amgen, Celgene, DS Pharma, Eli Lilly, Galapagos, Janssen-Cilag, Leo Pharma, Morphosis, MSD Novartis, Pfizer, Sandoz, Sanofi, UCB., Consultant of: Consultant: AbbVie, Almirall, Celgene, Dignity, Galapagos, Leo Pharma, Maruho, Mitsubishi, Novartis, Pfizer, Xenoport, Grant/research support from: Research support/principal investigator (clinical trials): AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Chugai, Dermira, DS-Pharma, Eli Lilly, Galderma, GSK, Janssen-Cilag, Leo, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, UCB, Elizabeth Colston Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Throup Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sudeep Kundu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Andrew Blauvelt Consultant of: Scientific adviser and/or clinical study investigator for AbbVie, Aligos, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma.

BackgroundTyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective, allosteric inhibitor of TYK2 that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA (NCT03881059). Results from the 16-week, placebo-controlled periods of two 52-week, Phase 3 trials in psoriasis (POETYK PSO-1 and POETYK PSO-2) previously showed that deucravacitinib was significantly more efficacious than placebo and apremilast based on the coprimary endpoints of ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at Week 16.ObjectivesTo evaluate the efficacy of deucravacitinib over 52 weeks in the POETYK PSO-1 and POETYK PSO-2 trials.MethodsPOETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were double-blinded trials that randomised patients with moderate to severe plaque psoriasis (body surface area involvement ≥10%, PASI ≥12, sPGA score ≥3) 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo were switched to deucravacitinib at Week 16 in both trials. Patients randomised to deucravacitinib in PSO-1 received deucravacitinib continuously through Week 52. PSO-2 included a randomised withdrawal phase in which patients originally randomised to deucravacitinib who had achieved PASI 75 response at Week 24 were rerandomised 1:1 to placebo or deucravacitinib, whereas those who did not achieve PASI 75 response at Week 24 continued receiving deucravacitinib. The proportions of patients achieving PASI 75 and sPGA 0/1 responses were evaluated up to Week 52. Secondary efficacy endpoints evaluated over this period included PASI 90, PASI 100, percentage change from baseline in PASI, sPGA 0 (clear), change from baseline in the Psoriasis Symptoms and Signs Diary (PSSD) symptom score, and Dermatology Life Quality Index (DLQI) 0/1 (no impact on patient’s life).ResultsA total of 666 and 1020 patients were randomised in PSO-1 and PSO-2, respectively. Demographic and baseline disease characteristics were balanced across treatment groups; mean age was 46.6 years, mean disease duration was 18.6 years, 18.4% of patients had PsA, and 34.8% had previously used biologic therapy. PASI 75, PASI 90, and PASI 100 responses were maintained from Week 16 to Week 52 in PSO-1 (Figure 1). Additionally, sPGA responses were maintained during this period (sPGA 0/1: 53.6% to 52.7%; sPGA 0: 17.5% to 23.5%, respectively). Patients who switched from placebo to deucravacitinib at Week 16 demonstrated PASI 75 and sPGA 0/1 responses at Week 52 (68.3% and 53.8%, respectively) comparable to those observed in patients who received continuous deucravacitinib treatment from Day 1 (65.1% and 52.7%, respectively). In PSO-2, among deucravacitinib-treated patients who achieved PASI 75 at Week 24 and were rerandomised to continue treatment, responses were maintained at Week 52 in the majority of patients (PASI 75, 80.4% [119/148]; sPGA 0/1, 70.3% [83/118]). Results for percentage change from baseline in PASI, change from baseline in the PSSD symptom score, and DLQI 0/1 were consistent with those reported for PASI and sPGA responses.ConclusionResults from the Phase 3 POETYK PSO-1 and PSO-2 trials demonstrated that deucravacitinib was efficacious through 52 weeks in patients with moderate to severe plaque psoriasis. Clinical responses were maintained in patients who received continuous deucravacitinib treatment and were improved in patients who switched from placebo at Week 16 to deucravacitinib treatment.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRichard B. Warren Consultant of: Consulting fees: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, Biogen, and UNION., Grant/research support from: Research grants: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB;, April Armstrong Grant/research support from: Grants and personal fees: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; Personal fees: Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work., Melinda Gooderham Consultant of: Advisory board, principal investigator, and lecture fees: Arcutis, Galderma, Leo Pharma, Pfizer, and Regeneron; Principal investigator and consulting fees: Akros Pharma and Kyowa Kirin; Advisory board, principal investigator, lecture fees, and consulting fees: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant; Principal investigator: Aslan, Bristol Myers Squibb, Dermavant, Dermira, GlaxoSmithKline, MedImmune, Merck, Roche Laboratories, and UCB., Bruce Strober Consultant of: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, Equillium, Janssen, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, Ortho Dermatologics, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, Ventyxbio, and vTv Therapeutics; Speaker: AbbVie, Eli Lilly, Janssen, and Sanofi Genzyme; Co-Scientific Director (consulting fee): CorEvitas’ Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas’ Psoriasis Registry, Dermavant, Dermira, and Novartis., Diamant Thaçi Speakers bureau: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Shinichi Imafuku Grant/research support from: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Taiho, Maruho, Tanabe Mitsubishi, Leo Pharma, Janssen, Sun Pharma, Torii, and Yakuhin; Personal fees: Amgen, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB., Howard Sofen Consultant of: Clinical Investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma., Lynda Spelman Consultant of: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma, Trius, UCB, and Zai Lab., Neil J Korman Speakers bureau: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme., Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech., Min Zheng Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly China, Leo Pharma China, Novartis China, Pfizer, Sanofi China, and Xian-Janssen., Elizabeth Colston Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Throup Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sudeep Kundu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Renata Kisa Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Employees and shareholders: Bristol Myers Squibb, Employee of: Employees and shareholders: Bristol Myers Squibb, Andrew Blauvelt Consultant of: Scientific advisor and/or clinical study investigator: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Vibliome.

Background:PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch.Objectives:To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA.Methods:Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1).Results:Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (p<0.0001); the effect of treatment attributable to factors other than ISI and PGA-PsO (direct effect) was not statistically significant (p=0.66). Results were consistent for pooled and individual study data. Because the direct effect was small and not statistically significant, the model was re-specified to exclude the direct effect of tofacitinib treatment on DLQI. In the revised model (pooled data), 17.7% of the indirect effect was attributable to PGA-PsO (p=0.0006) and 82.3% was attributable to itch (assessed by ISI) (p<0.0001) (Figure 2). Analyses of individual studies using the revised model gave results generally consistent with pooled data.Conclusion:Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienna

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA,1 and vs PBO or apremilast in 2 Phase 3 PsO trials.2ObjectivesTo assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials.MethodsThe Phase 2 double-blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double-blind PsO trials, POETYK PSO-1 and POETYK PSO-2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed.ResultsIn the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC-, PBO-, and apremilast-treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms.Table 1.Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16PsA Phase 2PsO Phase 3aCTCAE TermGradePlacebo (n=66)n (%)DEUC 6 mg QD (n=70)n (%)DEUC 12 mg QD (n=67)n (%)Placebo (n=419)n (%)DEUC 6 mg QD (n=842)n (%)Apremilast 30 mg BID (n=422)n (%)BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16Lymphocyte count decreased340000001 (1.4)00000001 (0.2)0001 (0.1)00000Neutrophil count decreased34000000000000001 (0.2)01 (0.1) 01 (0.1)00000Platelet count decreased34000000000000000000000000Anaemia340N/A0N/A0N/A0N/A0N/A0 N/A0N/A0N/A0N/A0 N/A0N/A1 (0.2) N/AAlanine aminotransferase increased34000 000000 0000 0000000000 0Aspartate aminotransferase increased34000000000 01 (1.6)0000 00 01 (0.1)0001 (0.2) 0CPK increased34001 (1.5) 0000 00001 (1.6)1 (0.2) 03 (0.7) 1 (0.2)1 (0.1) 05 (0.6) 6 (0.7)1 (0.2)02 (0.5) 1 (0.2)Cholesterol high3400000000000 00 00 00 00 00000Hypertriglyceridemia34000 01 (1.4) 1 (1.4)2 (2.9) 1 (1.4)1 (1.6) 04 (6.0) 02 (0.5) 1 (0.2)6 (1.5) 04 (0.5)1 (0.1)12 (1.5)2 (0.2)3 (0.7) 08 (2.0) 0aPOETYK PSO-1 and PSO-2 pooled data.BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week.ConclusionDEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two-thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRoy M. Fleischmann Consultant of: Abbvie, Acea, Akros, Amgen, Bristol Myers Squibb, Celtrion, Eli Lilly & Co., Galvani, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi Aventis, Taiho, and UCB., Grant/research support from: AbbVie, Acea, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly & Co., Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Pfizer, Roche/Genentech, Samumed, Sanofi Aventis, and UCB, Diamant Thaçi Consultant of: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Melinda Gooderham Consultant of: Investigator, speaker, advisory board member or consultant for: AbbVie, Akros, Amgen, Anaptys Bio, Arcutis, Aslan, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, SUN Pharma, and UCB., Bruce Strober Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi-Genzyme; Scientific co-director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis., Neil J Korman Consultant of: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi-Genzyme., Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Employees and shareholders of Bristol Myers Squibb, Employee of: Employees and shareholders of Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Akimichi Morita Consultant of: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Grant/research support from: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB;

BackgroundDrug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis [1-4].ObjectivesThe objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.MethodsWe performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.ResultsThe study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a generally higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis drug survival was generally highest for guselkumab.Figure 1.ConclusionDiffering treatment responses to drugs with various types of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.References[1]Egeberg A, Ottosen MB, Gniadecki R, et al. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol 2018; 178(2): 509-19.[2]Gron KL, Glintborg B, Norgaard M, et al. Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial. Arthritis Rheumatol 2019; 71(12): 1997-2004.[3]Lindstrom U, Glintborg B, Di Giuseppe D, et al. Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis. Rheumatology 2020.[4]Glintborg B, Lindstrom U, Di Giuseppe D, et al. One-year treatment outcomes of secukinumab versus tumor necrosis factor inhibitors in Spondyloarthritis. Arthritis Care Res (Hoboken) 2020.AcknowledgementsWe acknowledge the substantial contribution of the academic hospitals and private clinics and their physicians that report data to DANBIO and DERMBIO.Disclosure of InterestsAlexander Egeberg Speakers bureau: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Paid instructor for: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Consultant of: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals, Grant/research support from: Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Nana Lippert Rosenoe: None declared, David Aagaard: None declared, Erik Lørup: None declared, Lea Nymand: None declared, Lars Erik Kristensen Speakers bureau: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Paid instructor for: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Consultant of: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Grant/research support from: Dr. LE Kristensen has received fees for speaking and consultancy from Pfizer, AbbVie, Amgen, Forward pharma, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Jacob Thyssen Speakers bureau: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Paid instructor for: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Consultant of: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Grant/research support from: Dr. Thyssen has attended advisory boards for Almirall, Eli Lilly & Co, Pfizer, LEO Pharma, Asana, Regeneron, AbbVie, Union Therapeutics, and Sanofi-Genzyme and received speaker honorarium from LEO Pharma, Regeneron, Almirall, Abbvie, Eli Lilly & Co, and Sanofi-Genzyme, and been an investigator for AbbVie, Pfizer, Eli Lilly & Co, LEO Pharma and Sanofi-Genzyme., Simon F. Thomsen Speakers bureau: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Paid instructor for: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Consultant of: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., Grant/research support from: Dr. Thomsen has been a speaker or has served on advisory boards for Sanofi-Genzyme, AbbVie, LEO Pharma, Pfizer, Eli Lilly and Company, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi-Genzyme, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals; and has been an investigator for Sanofi-Genzyme, Regeneron, AbbVie, LEO Pharma, Novartis and Pfizer., René Lindholm Cordtz: None declared, Nikolai Loft Speakers bureau: speaker for Eli Lilly and Janssen Cilag., Lone Skov Speakers bureau: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Paid instructor for: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Consultant of: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Grant/research support from: Dr. Skov has been a paid speaker for AbbVie, Eli Lilly, Novartis, and LEO Pharma, and has been a consultant or has served on Advisory Boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi. She has served as an investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZenica, Eli Lilly, Novartis, Regeneron, and LEO Pharma, and has received research and educational grants from Novartis, Sanofi, Janssen Cilag, and LEO Pharma., Lars Erik Bryld: None declared, Mads Rasmussen Speakers bureau: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Paid instructor for: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Consultant of: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Grant/research support from: Dr. Rasmussen has been a paid speaker for AbbVie, Almirall, and LEO Pharma. Consulting, or serving on expert/advisory boards with AbbVie, Almirall, Janssen Cilag, and Eli Lilly. He served as investigator for Janssen Cilag, UCB, and Novartis., Pil Højgaard: None declared, Salome Kristensen: None declared, Lene Dreyer Speakers bureau: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Paid instructor for: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Consultant of: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma., Grant/research support from: Dr. Dreyer has received research grant/research support from BMS, and speakers bureau from Eli Lilly and Galderma.

Space debris has reached alarming proportions and is growing at a frightening pace, because of the expanding number of satellites circulating in Low Earth Orbit (LEO), designed to increase global Internet coverage and provide earth observation data. LEO satellites are now being launched in mega-constellations, including by Elon Musk's company SpaceX. It is time to completely overhaul the 1967 Outer Space Treaty, which was not designed to deal with current problems. The COP forum should therefore include the near-earth environment within its concept of the earth's climate, enabling the UN to acknowledge, as a collective, the growing menace of human-made debris in near-earth space, and, in partnership with the UN-Outer Space Affairs Office (UN-OOSA), call for a new declaration on LEO.

La nozione di identità, nelle sue molteplici declinazioni in senso culturale, storico e nazionale, rappresenta uno dei temi cardine al centro del dibattito dei Cultural Studies.molto solida come quella irlandese; è proprio questo tentativo complesso e ambizioso di ridefinizione che cercheremo di indagare nel corso di questo studio. Grazie alle analisi di Stuart Hall (1980), Paul Gilroy (1993)2, Iain Chambers (2003)3, Helene Cixous (2008)4, dovrebbe essere ormai assodato che parlare di identità fisse, rigide, essenziali, impermeabili ad ogni tipo di contaminazione sia una tesi difficile da sostenere e come sarebbe meglio parlare piuttosto di “formazioni identitarie”, costruzioni flessibili, posizionamenti e riposizionamenti continui.Si tratta di visioni dell’identità meno familiari, probabilmente destabilizzanti, ma che permettono di definire l’identità come pratica della differenza, attraverso una costante negoziazione con l’Altro che conduce alla continua modificazione del sé. È stata messa in discussione inoltre la presunta naturalità dell’identità nazionale: ne è stata svelata la struttura artificiale, da un lato mostrando come essa sia fondata sull’ ideazione di “comunità immaginate” (Anderson, 1983), sulla costruzione di un lessico specifico e sull’ “invenzione della tradizione” (Hobsbawm, 1997); dall’altro, decostruendo il forte nesso - solo apparentemente inscindibile - tra nascita e nazione che, dalla seconda metà dell’Ottocento, viene posto a fondamento dei diversi Stati-Nazione che fioriscono in tutta Europa. In questo, un ruolo determinante è stato svolto dalle teorie post-coloniali portate con forza sulla scena culturale globale da pensatori quali Edward Said (1978), Homi Bhabha (1994), Gayatri Spivak (1999) e riguardanti aree tematiche quali la critica al nazionalismo e al colonialismo, le condizioni di subalternità legate alla razza e al genere, le modalità di rappresentazione dell’Altro, la dialettica identità/differenza5. Tali contributi, che intaccano definitivamente l’essenzialismo identitario e le presunte “leggi dell’origine” su cui si fondano le identità nazionali, verranno presi in esame più dettagliatamente nel corso del lavoro di ricerca sia in quanto specifiche teorie a cui ricondurre le argomentazioni proposte, sia come strumenti concreti per interpretare i fenomeni che saranno descritti nel corso dell’analisi. Più o meno negli stessi anni in cui gli autori citati propongono le loro considerazioni a proposito del concetto e delle pratiche di identità, in Irlanda un gruppo di artisti e intellettuali - riunitosi sotto il nome di Field Day Theatre Company - si occupa di scomporre e riformulare una costruzione identitaria

Dans la vie sociale, les besoins sont regardés comme un préalable nécessaire à la définition d’un projet ou à la création d’un service. Pourtant s’ils apparaissent évidents, naturels, ils sont l’objet d’une construction sociale. Cette recherche se propose d’étudier le processus de fabrication des besoins sociaux dans la politique d’accueil des jeunes enfants en France en partant des questions suivantes : comment les besoins adviennent-ils sur la scène publique, dans quelle mesure sont-ils pris en considération, comment sont-ils exprimés ? Trois déterminants des besoins ont été au cœur de l’analyse : le politique, l’individu et le marché. Nous avons montré que les besoins sociaux reçoivent plusieurs formes de « mise en visibilité » pour exister publiquement mais que cette politisation aboutit partiellement à les faire reconnaître comme un vrai problème. Par ailleurs, la reconnaissance des besoins sociaux passe par leur transformation en une « demande sociale ». Dans le secteur de la petite enfance, cette expression est rendue difficile parce que la photographie des besoins qui ressort des enquêtes est très hétérogène, mais aussi en raison de l’existence d’une non-demande (le non-recours au service), et à cause des situations « d’imprévisibilité » dans lesquelles se trouvent les parents par rapport à leur mode d’accueil. Enfin, les besoins sont étroitement liés à ceux qui les couvrent. Dans le cadre du nouveau marché des crèches d’entreprise, un déplacement s’opère : les besoins des familles sont mis en arrière-plan au profit de ceux des entreprises et des collectivités financeurs et potentiels clients des services. Ceci étant, les entreprises de crèches continuent à faire exister les besoins des familles, autrement, de manière plus quantitative, notamment par les plates-formes de réservation de places et par la promotion de deux figures du parent, celle du « salarié-parent » et celle du « parent-prospect »
In social life, needs are considered as a necessary prerequisite to the definition of a project or the creation of a service. Though they seem obvious and natural, they result from a social construction. This research sets out to study the making process of social needs regarding child care policy in France from the following questions : how do needs arise on public scene, to what extent are they taken into consideration, how are they expressed ? Three determinative were at the heart of our analysis : politics, market and the individual. We have shown that social needs acknowledge several forms of “visibiliting” so as to exist on public scene but that actually this politicization partially succeeds in making them recognize as a real problem. On the other hand, the recognition of social needs goes through their transformation into one social request. In child care field, this expression turns out to be difficult, because the picture of the needs which emerge from surveys is very heterogeneous, owing to the existence of no-requesting (no-resorting to services), because of some situations of “unpredictability” in which parents cope with child minding. Finally, needs are closely linked to those who cover them. Within the context of the firm child care centres’ new market, a transfer has occurred : families’ needs have been relegated to the background to the profit of the firms and local communities’ ones :services’ financing and potential customers. Yet, market continues making families ‘ needs exist but differently, in a more quantitative way, in particular through child care centres’ websites and also by the promotion of both new faces of the parent : “salaried-parent” and “prospect-parent”

Superati «novant’anni d’impazienza» e dopo un lungo periodo votato all’autocommento e all’esplorazione delle proprie intenzioni, Raffaele La Capria ha raccolto le sue opere in due Meridiani curati da Silvio Perrella. La Capria ne ha celebrato l’uscita nella prolusione inaugurale di Salerno Letteratura, poi confluita nel breve autoritratto narrativo "Introduzione a me stesso" (2014). In questa sede, l’autore è tornato su alcuni punti essenziali della sua riflessione sulla scrittura, come la relazione, reciproca e ineludibile, fra tradizione e contemporaneità. All’epilogo del «romanzo involontario» di una vita, La Capria guarda retrospettivamente alla propria esperienza come ad un’autentica educazione intellettuale. Perciò, muovendo da un’intervista inedita del 2015, riportata integralmente in appendice, la tesi ha l’obiettivo di ricostruire l’apprendistato letterario di La Capria dai primi anni Trenta, quando l’autore ancora frequentava il ginnasio, fino all’inizio dei Sessanta, quando ottenne il premio che ne avrebbe assicurato il successo. Il percorso, che riesamina l’intera bibliografia lacapriana nella sua varietà e nella sua stratificazione, si articola in una serie di fasi interdipendenti: la partecipazione indiretta alle iniziative dei GUF (intorno alle riviste «IX maggio» e «Pattuglia»); l’incursione nel giornalismo e l’impegno culturale nell’immediato dopoguerra (sulle pagine di «Latitudine» e di «SUD»); l’attività di traduttore dal francese e dall’inglese (da André Gide a T.S. Eliot); l’impiego alla RAI come autore e conduttore radiofonico (con trasmissioni dedicate a Orwell, Stevenson, Saroyan e Faulkner); la collaborazione con «Il Gatto Selvatico», la rivista dell’ENI voluta da Enrico Mattei e diretta da Attilio Bertolucci; e le vicende editoriali dei suoi primi due romanzi, “Un giorno d’impazienza” (1952) e “Ferito a morte” (1961), fino alla conquista dello Strega. La rilettura dell’opera di uno scrittore semi-autobiografico come La Capria, attraverso il costante riscontro di fonti giornalistiche, testimonianze epistolari e documenti d’archivio che avvalorano e occasionalmente smentiscono la sua versione dei fatti, diventa allora un’occasione per immergersi nella sua mitografia personale e avventurarsi in territori finora poco esplorati: come la ricostruzione del suo profilo culturale, a partire dal milieu in cui La Capria vive e opera, o l’incidenza delle letture e delle esperienze giovanili sulla sua prassi letteraria.

Il volume è un testo interdisciplinare a più autori che effettua una comparazione fra le due differenti vie novecentesche alla modernizzazione di Italia e Romania - variamente ispirate da modelli esterni di riferimento -, dal punto di vista politologico, culturale-politico, politico-istituzionale e politico-economico, con particolare riferimento al problema della rappresentanza. Il volume si compone di sei saggi di diversa ispirazione metodologica ed ideologica ma accomunati dalla tematizzazione dei contesti culturali e giuridico-politici dei due paesi, intesi come sistemi in "transizione", sospesi fra ricerca delle proprie caratteristiche storiche e l'attenzione ai modelli più avanzati del mondo occidentale.

Quest’opera raccoglie gran parte delle pubblicazioni scientifiche di Paolo de Bartolomeis, Professore Ordinario di Geometria presso l’Università di Firenze dal 1980 fino alla prematura scomparsa, avvenuta il 29 novembre 2016. Gli articoli sono pubblicati in ordine cronologico. Dopo i primi lavori in Geometria Analitica Reale e, poi, in Analisi Complessa, lo sviluppo dei suoi interessi scientifici si intreccia con quello della Geometria Differenziale Complessa, con collaborazioni di altissimo livello internazionale. I due volumi di cui si compone quest’opera costituiscono così un prezioso riferimento per coloro che vorranno occuparsi dei temi di ricerca cari a Paolo de Bartolomeis, non solo per il contenuto scientifico, ma anche perché raccontano la storia di una grande passione e di una non comune apertura intellettuale; uno straordinario insegnamento per chi si avvicina o si dedica alla ricerca in Matematica e, in particolare, in Geometria.

Poco più di 150 pezzi epistolari, provenienti dagli archivi novecenteschi di Firenze e di Roma, pubblicati per la prima volta grazie all’attenta trascrizione di Alberto Baldi, consentono non solo di ricostruire la storia di un’amicizia nata intorno alle pagine dei giornali e consolidatasi nel tempo fino a coinvolgere le compagne dei due interlocutori (Gianna Manzini, Lina Baraldi e Luisa Babini), ma di seguire la presenza di Giuseppe Dessí su uno dei quotidiani più letti nella capitale. La corrispondenza editoriale (precocemente avviata da un Falqui animatore di cultura) si trasforma ben presto – tramite picchi di frequenza: dal ’48 al ’58 – nella consulenza di un lettore solidale a cui va il merito di avere fatto proseguire, nonostante i dissensi politici per la linea conservatrice del «Tempo», una collaborazione che avrebbe nutrito alcune delle più significative raccolte di racconti dello scrittore. Chiudono il libro trentotto testi narrativi di Dessí dispersi sulla «terza pagina», mai prima d’ora recuperati in volume.

Il primo di due volumi dedicati all'ermetismo e Firenze editi da Firenze University Press (il secondo dal titolo Luzi, Bigongiari, Parronchi, Bodini, Sereni è acquistabile separatamente). Tra il 1930 e il 1945 un gruppo di giovani dette vita, a Firenze, a una delle più felici stagioni letterarie del nostro Novecento, nota come ermetismo fiorentino (o ermetismo tout court). Gran parte dei partecipanti si riconobbe non solo in una dizione comune, marcata da un immaginario e da una sintassi condivisi, ma nel silenzioso dissenso dalla retorica del regime, alla quale venivano contrapposti la radicalità dell’istanza etica e il legame profondo con le radici giudaico-cristiane, romanze, romantico simboliste della civiltà europea. A cento anni dalla nascita dei suoi protagonisti ancora ci si chiede cosa sia stato l’ermetismo, come sia nato, cosa l’abbia contraddistinto, quali segni abbia subìto e lasciato. Cercare come si sia modificato, perché sia stato circondato da passione, pregiudizi e avversione (come fanno i due imprescindibili volumi che raccolgono gli atti di un memorabile convegno nel quale Anna Dolfi ha coinvolto studiosi provenienti da ogni parte del mondo), porta non solo a tracciare un quadro/ritratto degli autori dell’ermetismo, dei loro estimatori e/o detrattori, ma a delimitare le costanti e i confini di un complesso capitolo della storia italiana iniziata con il Fascismo e conclusa, di recente, con la caduta delle ideologie. Tra maestri, compagni, seguaci, le figure di Bo, Macrí, Luzi, Bigongiari, Parronchi, Bodini, dell’amico di generazione Sereni, spiccano e si impongono per la forza di una suggestiva esperienza di scrittura ad alto tasso meditativo, nella critica come in traduzione, in narrativa come in poesia.

Il secondo di due volumi dedicati all'ermetismo e Firenze editi da Firenze University Press (il primo dal titolo Critici, traduttori, maestri, modelli è acquistabile separatamente). Tra il 1930 e il 1945 un gruppo di giovani dette vita a Firenze a una delle più felici stagioni letterarie del nostro Novecento. Molti di loro si riconobbero in una dizione comune, marcata da un immaginario condiviso, e nel silenzioso dissenso dalla retorica del regime, alla quale venivano contrapposti la radicalità dell’istanza etica e il legame profondo con le radici giudaicocristiane, romanze, romantico-simboliste della civiltà europea. A cento anni dalla nascita dei suoi protagonisti (Mario Luzi, Piero Bigongiari, Alessandro Parronchi, Vittorio Bodini) ancora ci si chiede cosa sia stato l’ermetismo, come sia nato, cosa l’abbia contraddistinto. Cercare come si sia modificato, perché sia stato circondato da pregiudizi e avversione (come fanno i due imprescindibili volumi che raccolgono gli atti di un memorabile convegno nel quale Anna Dolfi ha coinvolto studiosi provenienti da ogni parte del mondo), porta a tracciare un quadro/ritratto degli autori dell’ermetismo, dei suoi critici (Bo, Macrí), amici (il compagno di generazione Vittorio Sereni), estimatori e/o detrattori, e a delimitare i confini di un complesso capitolo della storia italiana iniziata con il Fascismo e conclusa, di recente, con la caduta delle ideologie. Assieme ai suoi ‘attori’, in posizione di rilievo è Firenze, la città che fu risvegliata per qualche decennio alla grandezza del passato da una nuova passione, fatta di cultura, creatività ed intelligenza.

One critical tool for the struggle for equality and liberation is the Boycott, Divestment, and Sanctions Movement (BDS), a vibrant, global movement, launched in 2005, to end ‘international support for Israel’s oppression of Palestinians and pressure Israel to comply with international law.’ I believe this, now more than ever, just like when comrades before us organized for the dismantling of political apartheid in South Africa and were told they are imagining the impossible, they organized and they were victorious against political apartheid. The struggle continues. I do believe there will come a day when Zionism and racism will fall. The only question we are facing is how fast it will fall. BDS is one of the paths of resistance to make that collapse of apartheid faster. The question is not whether Zionism and apartheid in Palestine will be eliminated; the question is: how fast. Let us work together to make the fall of apartheid faster, and the liberation of Palestine sooner.

This chapter discusses how Leo Wharton got into the film industry. Leo's earliest documented stage appearance was in 1893, in the play The Fairies' Well. After a few years of itinerant acting, Leo was able to secure steadier employment at the Hopkins Grand Opera in Saint Louis, where his brother Ted was already performing. As part of Colonel Hopkins's theatrical company, Leo assumed various stage roles in the popular daylong “continuous performance” programs that Hopkins pioneered, which combined live drama and between-the-acts vaudeville. Leo's first known (and first credited) film appearance was in the title role of Lincoln in Abraham Lincoln's Clemency (1910), a photoplay produced by Ted Wharton for Pathé. The role not only garnered good reviews for his sympathetic performance and even for his resemblance to the revered figure whom he was portraying; it also led to an offer as a director for Pathé, the studio for which Ted was then working. There, Leo began directing similar shorts, such as the period historical drama The Rival Brothers' Patriotism (1911). Since early movie audiences seemed especially fond of marital comedies, Leo produced several shorts in 1913 that revolved around wedding-day complications. While these and other short pictures that Leo produced for Pathé were often predictable in their plotting and formulaic in their execution, they were nonetheless popular with audiences and profitable for Pathé. Moreover, they established his reputation in the industry.

Abstract After leaving graduate school, I was employed by a government contractor, the Geotech Company in Alexandria, Virginia, where I analyzed oceanographic data. When I joined the company in 1967, the staff directory was reprinted, and we were 127 persons strong. Photoreduction was required to make the list of names fit on a single page. After about 6 months, however, I became concerned as I watched this work force being reduced. Friday seemed to be the day people were let go. On the Monday morning after each of these Fridays, I noticed that the staff directory did not have to be reduced as much. When the staff had dwindled to 61, I resigned and went to work for an oil company. I left believing that just about nobody was going to have an entire career and retire normally from the government-contracting business-not from this company and probably not from any contract research company on the beltway that surrounds the nation ‘s capital.

Abstract William Henry Dall (1845-1927) grew up in Boston and attended Harvard but never graduated. In 1866 he ac companied the historic Western Union Telegraphy Company expedition to Alaska, which sought to find an overland route for a transcontinental telegraph line to Europe. This objective proved impossible to achieve, but Dall later produced an important book as a result of his adventures in the north, Alaska and Its Resources (Lee and Shepard, 1870). From 1871-1884 Dall served in the U.

The co-author of The Responsible Company: Patagonia’s First 40 years describes how work at the clothing company he helped start became increasingly meaningful and satisfying over the decades as, beginning with a switch from conventional to organic cotton, Patagonia tackled increasingly difficult social and environmental problems in its operation and supply chain. Stanley draws on two papal encyclicals, Leo XIII’s Rerum Novarum(1891) and Francis’s Laudato Si (2015), and Catholic social justice principles of solidarity and subsidiarity, to illustrate the need and the possibility, in a time of social and environmental crisis, for business to mobilize its productive capacity to help regenerate human communities and the natural world; this would be meaningful work of the highest order.

An analysis of the strategies of the NIBCO Company of Reynosa to compensate intellectual capital during the Covid-19 pandemic is presented. The objective is to know what are the reasonings that led the company to implement compensation strategies in favor of its intellectual capital in response to the COVID-19 pandemic and its possible impacts on its productivity. A non-experimental, descriptive, and cross-sectional methodological design is used. Information collected through the method of interviews with managers and administrators of the same is analyzed. It is concluded that the company reacted favorably towards its intellectual capital, strengthening it through a scheme of additional compensation so that the staff can face greater financial and social security capacity, the effects of this new disease on health, and the disruption of daily forms and lifestyles.

Many activities of daily living during work, exercise, religious worship, and hobbies require deep knee flexion. Activities such as rising from a low chair or getting into or out of a bath require between 100° and 160° of knee flexion [1]. Other activities such as kneeling or squatting to pick an item off the ground can be difficult with a limited range of motion. Beside deep knee flexion being important for daily living activities, it is essential in non-Western cultures that commonly sit in deep knee-bending positions. In vitro studies looking at knee function often focus solely on the knee joint, ignoring the effect of the muscle, ligament, and tendon constraints of the ankle, and simplifying or neglecting muscle loads. The effects of these assumptions on kinematics are unknown. The purpose of this study was to compare a squatting activity for: 1) whole leg versus knee specimens, and 2) different combinations of quadriceps and hamstrings loading.

Abstract In the Bonga Deepwater project, while exploring subsea well intervention and stimulation campaign opportunity, the subsea Rigless intervention strategy, which has been in the SNEPCo team's technology maturation funnel for some years, re-surfaced. In the first quarter of 2017, the Shell Nigeria Exploration and Production Company (SNEPCo) Deepwater team led the industry to deploy the first ever riser-less technology for well intervention operations in Nigeria. The main objective was to prove the rigless intervention concept and capability in the Bonga Deepwater project. The team focused on improving production enhancement and sustaining well integrity on the Bonga Main Project by minimizing well-intervention cost without compromising process safety, achieving incident free operation, and delivered the project at 50% less than what this scope of work would have cost using a Mobile Offshore Drilling Unit (MODU). Additionally, the acid stimulations added 9,200 barrels of crude oil per day to the company's production. As with every new project, several challenges were encountered, and new ideas were developed. The team acquired a lot of learning from the planning phase, vessel mobilization to execution. These learnings have been integrated into the team's standard operating procedure and shared with other stakeholders. Additionally, the knowledge and learnings gained from this project have been harnessed in collaboration with the service provider and Original Equipment manufacturer (OEM) to modify and upgrade an existing in-house well intervention well control package (EDP/LRP) for riserless intervention access in the Bonga Deepwater project.

Numerical study using actuator-line method based Large Eddy Simulation (LES) has been performed to understand the role of atmospheric stability on the wake effects of horizontal-axis full-scale 5-MW wind turbine (WT). The paper will specifically focus on using specific instances in the diurnal cycle corresponding to stable, neutral and unstable ABL state to gain understanding on the transient aerodynamics of a wind turbine throughout the diurnal cycle. Capturing accurate Atmospheric Boundary Layer (ABL) characteristics is key factor in improving the accuracy of WT model predictions as turbulence developed in the ABL has potential to adversely affect the fatigue lifetime and performance of wind turbines. ABL simulations for the diurnal cycle are performed to isolate the key ABL metrics such as surface momentum flux, boundary layer height, surface temperature flux, wind shear, and temperature gradient that influence the wake evolution of WT. Precursor ABL inflow is generated for the WT simulations. The positive heat flux on the surface causes high vertical velocity fluctuations described with streaks and updraft motions during the day while surface cooling rates result in increased shear and strong temperature gradients during the night. The surface temperature, geostrophic wind velocity, heating/cooling rates, and period of the diurnal cycle are varied in different simulations to compare turbulent statistics and the helical vortices of the wind turbine wake. The results have revealed surface temperature and surface flux are the important ABL metrics that have a strong effect on altering the turbulence in the WT wake. In addition, instabilities related to WT blade rotation exhibit sensitivity to ABL metrics. The positive heat flux shows higher mixing and causes large wake movement in the day-time conditions. The results aid in quantifying the movement of the wake at different times of the diurnal cycle. During night-time conditions mixing is low, causing slower wake recovery times. This is the first study to clearly isolate the key ABL metrics that influence the full-scale WT near-wake effects The study has implications in improving the predictions of WT power loss due to wake deficits. Further, this study sets an important direction on future modeling studies in identifying the ABL conditions in a diurnal cycle that influence the WT wake evolution.

Abstract For an upstream oil and gas company, avoiding an offshore COVID-19 outbreak while executing four different offshore projects poses a huge challenge, particularly in a country experiencing a daily COVID-19 test positivity rate over 20%. Even minor mismanagement of the quarantine process can lead to an offshore COVID-19 outbreak, with the risk of shutting down campaigns and severely impacting business objectives. The challenge is therefore to avoid an offshore COVID-19 outbreak, ensuring well-being of personnel during the quarantine period and managing quarantine related costs, including COVID-19 test costs. To ensure effective quarantine management, a new approach was created that applied a combination of medical assessments, Health & Safety (H&S) and security measures. Quarantine management was led by a special task force responsible for ensuring the readiness of transportations, rooms, PCR tests, as well as overall compliance to quarantine rules. In compliance with government regulations and WHO recommendations, another complimentary approach was applied that sequestered personnel who tested positive in an isolation room. Effective quarantine management was established with the assistance of the company Business Continuity Management Team (BCMT). The company was able to complete four different major offshore projects with no offshore COVID-19 outbreaks. During these operations, over 1,000 personnel were quarantined and tested with a 5.37% positivity rate at the pre-work quarantine site. Confirmed cases were managed in full compliance with government regulations. The result of this effective quarantine management system, has allowed the company to achieve scorecard performance goals while delivering all four of the major offshore work-scopes, as per the original business plan. This paper discusses quarantine management as part of business continuity management covering medical assessment, H&S and security measures amidst a national COVID-19 pandemic. These programs were applied in an adaptive method-based risk assessment, which based on evidence base approaches, during frequently changing government regulations.

Abstract This paper presents a novel approach to finding solutions to unsafe work practices in oil and gas environments—from manufacturing facilities to offshore platforms. The ‘Center of Excellence’ approach is a stepwise process for classifying safety events and harnessing data to reduce incidents during offshore oil and gas E&P activities. The approach includes identifying focus topics related to unsafe practices, forming cross-functional teams with significant field or impacted personnel participation, developing and implementing measures, utilizing the hierarchy of controls to mitigate the issue, and raising company-wide awareness through training and targeted information campaigns. The Center of Excellence process gives top priority to those activities in order to reduce the highest severity and most frequent safety incidents. The teams are then able to more clearly identify feasible solutions, including engineering controls, training, campaigns, and procedures to contain the hazards. The active engagement and involvement of frontline employees who either work in the field or on the factory floor is critical to understand the daily hazards of their work activities and the success of the Center of Excellence approach. With these employees acting as a champion of the developed solution, other workers are more likely to accept and adopt it in their daily routine. This paper reviews practical examples of how the Center of Excellence approach has led to safer practices in the workplace. Examples include improved safety measures for using tightening tools, which led to more than 50% reduction in hand injuries and other safety incidents. A recent example of using the approach to develop safer practices during manual handling of loads (MHL) is also presented. The examples highlight the benefits of bringing multifaceted teams and multiple industry-accepted safety concepts together to resolve common work safety challenges, which can serve as a blueprint for oil and gas companies to reduce incidents across their enterprise.

This paper presents the recent neutronics analysis results of a proposed LEU-fueled research reactor. The main goal of the research reactor is to provide advanced neutron source with a particular emphasis on high intensity cold neutron sources. A tank-in-pool type reactor with an innovative horizontally split compact core was developed in order to maximize the yield of the thermal flux trap in the reflector area. The reactor was designed with 20 MW thermal power and 30-day operating cycle. For non-proliferation purposes, the LEU fuel (U3Si2-Al) with 19.75 wt.% enrichment was used. The estimated maximum thermal flux of the reactor is ∼5×1014 n/cm2-s. The total peaking factor of the start-up (SU) core is ∼2.5. The calculated brightness of the cold neutron source (CNS) demonstrates the superiority of the cold neutron performance of the design.

This paper describes the Design, Engineering, Planning and Implementation activities that led up to an advanced, state of the art, optimum and economical solution for expanding an existing system to handle an increase of crude oil throughput from 80 to 117 mta metric tons per year (2.53 t/s to 3.71 t/s). The growing demand and reduced net imports of products will increase Western European crude oil requirements to 11 million b/d (barrel per day) equivalent to 20.24 m3/s by year 2000. SUMED (gulf of SUez - MEDiterranean) the Arab Petroleum Pipelines Company has historically secured about 40% of the market for middle Eastern crude oil movements to Europe. Given these market shares on incremental volume SUMED should achieve its maximum design throughput of 117 mta by year 2000. The SUMED pipelines system which is owned and operated by an Arab company having EGYPT, SAUDI ARABIA, KUWAIT, EMIRATES AND QATAR as share holders has been in operation since 1977. An expansion project has started to increase the throughput capacity of the system from 80 to 117 mta. The project completion is expected by mid 1994 with a total expenditure of 120 million dollars. This paper reviews the evaluation and selection of various electric motor and gas turbines for the main pumping station addition for this pipeline expansion.

Nowadays, a lot of companies are faced with the urgency of change in their daily operations. This is especially relevant in modern business development conditions when constant changes are considered critical for a company to adapt to market requirements and the global economic situation. The paper presents the audit of the most famous change management models. Change management is an endless cycle, and it requires a sound vision, plan, time, aptitudes, inspiration, monetary and automatic endeavors to execute the change. Successful change management is a venture and contributes to a hierarchical turn of events. There are a few models of change management available and choosing the right change management model is vital for leading or guiding productive and smooth transitions. The main goal of this paper is to describe the main differences between the well-known change management models by reviewing the relevant literature. The analysis led to the conclusion that it is impossible to pick up an optimal approach to change management. Every approach to change management attracts attention to various aspects of this problem; however, they do not exclude but complement each other.

Development of a MEMS-based (Micro Electro Mechanical System) components and subsystems has been pursued at Uppsala University, Sweden since 1997. Since 2005, the continued development towards the first flight the subject MEMS products onboard a satellite in 2008 is done within the frame of NanoSpace — a company dedicated to MEMS-based products for space. Currently, two major efforts to develop MEMS-based propulsion products are ongoing. First, NanoSpace is developing a miniaturized cold gas propulsion system. The major challenge in this effort is to develop the thruster module containing four individual thrusters with the capability to deliver proportional, low noise thrust in the micro- to milli-Newton range. The thruster pod even includes valves, filters, pressure- and temperature sensors and heaters. In a future step, even control electronics and a CAN interface will be included in the thrusters pod which has the size of a golf ball and a weight of about 100 grams. A prototype of this miniaturized cold gas propulsion will be flight tested onboard the PRISMA satellite. PRISMA is an international technology demonstration program with focus on rendezvous and formation flying. It is a two satellite LEO mission with a launch scheduled to September 2008. The other major development effort underway is a MEMS-based Xenon flow control system intended for electrical propulsion systems. Using MEMS technology, a Xenon feed system including an micro isolation valve, pressure regulator, and a number of parallel flow control modules can be built with significantly reduced size and mass compared to existing systems based on conventional technology. NanoSpace is a Swedish company with the goal to be a component and subsystem supplier of MEMS-based products to space industry, based on own research and development and intellectual property rights.

Abstract The oil industry is experiencing a critical situation as the Covid-19 pandemic outbreak. There are several challenges that facing the industry specially the investors as the global decline in demand for Energy merchandises, the future exploration and development drilling in new assets that require massive investments is still uncertain based on the current market price and conditions. The much-reported fall in oil prices and the acute pressure on IOCs to survive in this environment led the companies to stop many ongoing projects and shrink work profile that affected the oil production all over the world. The situation in Egypt is quite challenging for the investors as Egypt is a big consumer, along with the political stability that kept the economy running directed the big IOCs to embrace innovative approaches to lower the operating costs that has the direct impact on the cost per barrel to support maintaining the country growth and secure current energy demand. Dragon Oil company as newly introduced to Egypt's market after acquiring the market shares of one of the major joint ventures in Egypt (Gulf of Suez Petroleum Company- GUPCO) in October 2019 has faced the same dilemma of exerted pressure on the expenditures (Capex and Opex) in order to cope with the global market circumstances. However that didn't deter the company to embrace an innovative way of thinking and handling for the situation. Dragon Oil/GUPCO multi-disciplinary teams achieved successfully a production incremental increase of 10,000 barrels per day through the past six month by adapting a strategic management innovative plans, alternative lower cost technical solutions, production optimization and introducing new proved technologies to the 50 years old assets. This paper will highlight the complete workflow adopted by GUPCO/Dragon Oil teams covering the whole process aspects; appraise, select, define and execution phases to achieve the company goals. The work done was including restoring production from Shut-in offshore platforms or wells via fixing the surface network using neoteric solutions, widely applying rigless interventions using several new techniques in the current producers to maximize their production and optimizing the production cycle across the four production chokes In Summary, Dragon Oil/GUPCO teams managed to increase GUPCO's production despite of the restricted budget and the negative impact of COVID-19 pandemic on the oil price and reach an outstanding performance in operation excellence and safety aspects that results in arresting the natural decline and increase the growth production by about 15% from the 2019 Average production.

The first use of radiographic standards for inspection and acceptance of finished girth welds was adopted by API in 1953. This standard was largely based on the Unfired Pressure Vessel Code� which was adopted by ASME in 1931. At that time and to this day, weld defect acceptance standards are based on workmanship principles. In other words, the so called "Workmanship defect acceptance standards"� reflect the weld quality levels produced by. a trained welder using satisfactory materials, equipment and procedures. For many years exclusive use was made of the API 1104 workmanship defect acceptance levels for all field pipeline and related facilities welds. This, and very similar defect acceptance standards (e.g. BS 4515, CSA 2184, AS 1697, etc.) are used in many countries throughout the world. Though the specified acceptance levels have no scientific basis, the use of workmanship standards has provided an adequate level of quality control for many years. Particularly worthy of attention in this context is the fact that the currently stipulated levels have been developed for welds in lower strength pipe grades. Unfortunately, the developments in acceptance levels have not kept pace with those occurring in-pipeline technology. Furthermore, pipe size, strength and toughness, weld metal properties or pipeline operating conditions are not considered in the present-day defect acceptance standards. Problems of this kind have led companies involved in gas/oil transporting activities to develop their own standard requirements or at least to produce a supplement to the general standards. This report describes the results of an investigation into the engineering significance of girth weld defect acceptance criteria based upon weld quality (or workmanship) considerations. To this end, research efforts were divided into a theoretical and an experimental part. The theoretical study involved a comparison of internationally used weld quality standards and codes for pipeline welding in order to identify the general features common to them and to obtain a clear view of the different acceptability criteria. The experimental part was designed to provide factual information on the failure behaviour of defective girth welds in large pipe diameter pipe lines. The focal point of the experimental examinations was to compare, on the basis of wide plate test specimen behaviour, the performance levels of girth welds containing planar weld defects which were grossly out of tolerance with respect to most present-day weld quality (workmanship standards) specifications.

A mature teacher who continuously seeks improvement should be recognised as a professional who has autonomy in conducting their job and has the autonomy to engage in a professional community of practice (Hyslop-Margison and Sears, 2010). In other words, teachers’ engagement in professional development activities should be driven by their own determination rather than extrinsic sources of motivation. In this context, teachers’ self-determination can be defined as a feeling of connectedness with their own aspirations or personal values, confidence in their ability to master new skills, and a sense of autonomy in planning their own professional development path (Stupnisky et al., 2018; Eyal and Roth, 2011; Ryan and Deci, 2000). Previous studies have shown the advantages of providing teachers with autonomy to determine personal and professional improvement. Bergmark (2020) found that giving teachers the opportunity to identify areas of improvement based on teaching experience expanded the ways they think and understand themselves as teachers and how they can improve their teaching. Teachers who plan their own improvement showed a higher level of curiosity in learning and trying out new things. Bergmark (2020) also shows that a continuous cycle of reflection and teaching improvement allows teachers to recognise that the perfect lesson does not exist. Hence, continuous reflection and improvement are needed to shape the lesson to meet various classroom contexts. Moreover, Cheon et al. (2018) found that increased teacher autonomy led to greater teaching efficacy and a greater tendency to adopt intrinsic (relative to extrinsic) instructional goals. In developed countries, teacher autonomy is present and has become part of teachers’ professional life and schools’ development plans. In Finland, for example, the government is responsible for providing resources and services that schools request, while school development and teachers’ professional learning are integrated into a day-to-day “experiment” performed collaboratively by teachers and principals (Niemi, 2015). This kind of experience gives teachers a sense of mastery and boosts their determination to continuously learn (Ryan and Deci, 2000). In low-performing countries, distributing autonomy of education quality improvement to schools and teachers negatively correlates with the countries’ education outcomes (Hanushek et al., 2011). This study also suggests that education outcome accountability and teacher capacity are necessary to ensure the provision of autonomy to improve education quality. However, to have teachers who can meet dynamic educational challenges through continuous learning, de Klerk & Barnett (2020) suggest that developing countries include programmes that could nurture teachers’ agency to learn in addition to the regular content and pedagogical-focused teacher training materials. Giving autonomy to teachers can be challenging in an environment where accountability or performance is measured by narrow considerations (teacher exam score, administrative completion, etc.). As is the case in Jakarta, the capital city of Indonesia, teachers tend to attend training to meet performance evaluation administrative criteria rather than to address specific professional development needs (Dymoke and Harrison, 2006). Generally, the focus of the training relies on what the government believes will benefit their teaching workforce. Teacher professional development (TPD) is merely an assignment for Jakarta teachers. Most teachers attend the training only to obtain attendance certificates that can be credited towards their additional performance allowance. Consequently, those teachers will only reproduce teaching practices that they have experienced or observed from their seniors. As in other similar professional development systems, improvement in teaching quality at schools is less likely to happen (Hargreaves, 2000). Most of the trainings were led by external experts or academics who did not interact with teachers on a day-to-day basis. This approach to professional development represents a top-down mechanism where teacher training was designed independently from teaching context and therefore appears to be overly abstract, unpractical, and not useful for teachers (Timperley, 2011). Moreover, the lack of relevancy between teacher training and teaching practice leads to teachers’ low ownership of the professional development process (Bergmark, 2020). More broadly, in the Jakarta education system, especially the public school system, autonomy was never given to schools and teachers prior to establishing the new TPD system in 2021. The system employed a top-down relationship between the local education agency, teacher training centres, principals, and teachers. Professional development plans were usually motivated by a low teacher competency score or budgeted teacher professional development programme. Guided by the scores, the training centres organised training that could address knowledge areas that most of Jakarta's teachers lack. In many cases, to fulfil the quota as planned in the budget, the local education agency and the training centres would instruct principals to assign two teachers to certain training without knowing their needs. Realizing that the system was not functioning, Jakarta’s local education agency decided to create a reform that gives more autonomy toward schools and teachers in determining teacher professional development plan. The new system has been piloted since November 2021. To maintain the balance between administrative evaluation and addressing professional development needs, the new initiative highlights the key role played by head teachers or principals. This is based on assumption that principals who have the opportunity to observe teaching practice closely could help teachers reflect and develop their professionalism. (Dymoke and Harrison, 2006). As explained by the professional development case in Finland, leadership and collegial collaboration are also critical to shaping a school culture that could support the development of professional autonomy. The collective energies among teachers and the principal will also direct the teacher toward improving teaching, learning, and caring for students and parents (Hyslop-Margison and Sears, 2010; Hargreaves, 2000). Thus, the new TPD system in Jakarta adopts the feature of collegial collaboration. This is considered as imperative in Jakarta where teachers used to be controlled and join a professional development activity due to external forces. Learning autonomy did not exist within themselves. Hence, teachers need a leader who can turn the "professional development regulation" into a culture at schools. The process will shape teachers to do professional development quite autonomously (Deci et al., 2001). In this case, a controlling leadership style will hinder teachers’ autonomous motivation. Instead, principals should articulate a clear vision, consider teachers' individual needs and aspirations, inspire, and support professional development activities (Eyal and Roth, 2011). This can also be called creating a professional culture at schools (Fullan, 1996). In this Note, we aim to understand how the schools and teachers respond to the new teacher professional development system. We compare experience and motivation of different characteristics of teachers.

Background PHS (pulmonary hypertension syndrome, ascites syndrome) is a serious cause of loss in the broiler industry, and is a prime example of an undesirable side effect of successful genetic development that may be deleteriously manifested by factors in the environment of growing broilers. Basically, continuous and pinpointed selection for rapid growth in broilers has led to higher oxygen demand and consequently to more frequent manifestation of an inherent potential cardiopulmonary incapability to sufficiently oxygenate the arterial blood. The multifaceted causes and modifiers of PHS make research into finding solutions to the syndrome a complex and multi threaded challenge. This research used several directions to better understand the development of PHS and to probe possible means of achieving a goal of monitoring and increasing resistance to the syndrome. Research Objectives (1) To evaluate the growth dynamics of individuals within breeding stocks and their correlation with individual susceptibility or resistance to PHS; (2) To compile data on diagnostic indices found in this work to be predictive for PHS, during exposure to experimental protocols known to trigger PHS; (3) To conduct detailed physiological evaluations of cardiopulmonary function in broilers; (4) To compile data on growth dynamics and other diagnostic indices in existing lines selected for susceptibility or resistance to PHS; (5) To integrate growth dynamics and other diagnostic data within appropriate statistical procedures to provide geneticists with predictive indices that characterize resistance or susceptibility to PHS. Revisions In the first year, the US team acquired the costly Peckode weigh platform / individual bird I.D. system that was to provide the continuous (several times each day), automated weighing of birds, for a comprehensive monitoring of growth dynamics. However, data generated were found to be inaccurate and irreproducible, so making its use implausible. Henceforth, weighing was manual, this highly labor intensive work precluding some of the original objectives of using such a strategy of growth dynamics in selection procedures involving thousands of birds. Major conclusions, solutions, achievements 1. Healthy broilers were found to have greater oscillations in growth velocity and acceleration than PHS susceptible birds. This proved the scientific validity of our original hypothesis that such differences occur. 2. Growth rate in the first week is higher in PHS-susceptible than in PHS-resistant chicks. Artificial neural network accurately distinguished differences between the two groups based on growth patterns in this period. 3. In the US, the unilateral pulmonary occlusion technique was used in collaboration with a major broiler breeding company to create a commercial broiler line that is highly resistant to PHS induced by fast growth and low ambient temperatures. 4. In Israel, lines were obtained by genetic selection on PHS mortality after cold exposure in a dam-line population comprising of 85 sire families. The wide range of PHS incidence per family (0-50%), high heritability (about 0.6), and the results in cold challenged progeny, suggested a highly effective and relatively easy means for selection for PHS resistance 5. The best minimally-invasive diagnostic indices for prediction of PHS resistance were found to be oximetry, hematocrit values, heart rate and electrocardiographic (ECG) lead II waves. Some differences in results were found between the US and Israeli teams, probably reflecting genetic differences in the broiler strains used in the two countries. For instance the US team found the S wave amplitude to predict PHS susceptibility well, whereas the Israeli team found the P wave amplitude to be a better valid predictor. 6. Comprehensive physiological studies further increased knowledge on the development of PHS cardiopulmonary characteristics of pre-ascitic birds, pulmonary arterial wedge pressures, hypotension/kidney response, pulmonary hemodynamic responses to vasoactive mediators were all examined in depth. Implications, scientific and agricultural Substantial progress has been made in understanding the genetic and environmental factors involved in PHS, and their interaction. The two teams each successfully developed different selection programs, by surgical means and by divergent selection under cold challenge. Monitoring of the progress and success of the programs was done be using the in-depth estimations that this research engendered on the reliability and value of non-invasive predictive parameters. These findings helped corroborate the validity of practical means to improve PHT resistance by research-based programs of selection.

Banco de la República provides a comprehensive overview of Colombia’s finan¬cial infrastructure in its Payment Systems Report, which is an important product of the work it does to oversee that infrastructure. The figures published in this edition of the report are for the year 2020, a pandemic period in which the con¬tainment measures designed and adopted to alleviate the strain on the health system led to a sharp reduction in economic activity and consumption in Colom¬bia, as was the case in most countries. At the start of the pandemic, the Board of Directors of Banco de la República adopted decisions that were necessary to supply the market with ample liquid¬ity in pesos and US dollars to guarantee market stability, protect the payment system and preserve the supply of credit. The pronounced growth in mone¬tary aggregates reflected an increased preference for liquidity, which Banco de la República addressed at the right time. These decisions were implemented through operations that were cleared and settled via the financial infrastructure. The second section of this report, following the introduction, offers an analysis of how the various financial infrastructures in Colombia have evolved and per¬formed. One of the highlights is the large-value payment system (CUD), which registered more momentum in 2020 than during the previous year, mainly be¬cause of an increase in average daily remunerated deposits made with Banco de la República by the General Directorate of Public Credit and the National Treasury (DGCPTN), as well as more activity in the sell/buy-back market with sovereign debt. Consequently, with more activity in the CUD, the Central Securi¬ties Depository (DCV) experienced an added impetus sparked by an increase in the money market for bonds and securities placed on the primary market by the national government. The value of operations cleared and settled through the Colombian Central Counterparty (CRCC) continues to grow, propelled largely by peso/dollar non-deliverable forward (NDF) contracts. With respect to the CRCC, it is important to note this clearing house has been in charge of managing risks and clearing and settling operations in the peso/dollar spot market since the end of last year, following its merger with the Foreign Exchange Clearing House of Colombia (CCDC). Since the final quarter of 2020, the CRCC has also been re¬sponsible for clearing and settlement in the equities market, which was former¬ly done by the Colombian Stock Exchange (BVC). The third section of this report provides an all-inclusive view of payments in the market for goods and services; namely, transactions carried out by members of the public and non-financial institutions. During the pandemic, inter- and intra-bank electronic funds transfers, which originate mostly with companies, increased in both the number and value of transactions with respect to 2019. However, debit and credit card payments, which are made largely by private citizens, declined compared to 2019. The incidence of payment by check contin¬ue to drop, exhibiting quite a pronounced downward trend during the past last year. To supplement to the information on electronic funds transfers, section three includes a segment (Box 4) characterizing the population with savings and checking accounts, based on data from a survey by Banco de la República con-cerning the perception of the use of payment instruments in 2019. There also is segment (Box 2) on the growth in transactions with a mobile wallet provided by a company specialized in electronic deposits and payments (Sedpe). It shows the number of users and the value of their transactions have increased since the wallet was introduced in late 2017, particularly during the pandemic. In addition, there is a diagnosis of the effects of the pandemic on the payment patterns of the population, based on data related to the use of cash in circu¬lation, payments with electronic instruments, and consumption and consumer confidence. The conclusion is that the collapse in the consumer confidence in¬dex and the drop in private consumption led to changes in the public’s pay¬ment patterns. Credit and debit card purchases were down, while payments for goods and services through electronic funds transfers increased. These findings, coupled with the considerable increase in cash in circulation, might indicate a possible precautionary cash hoarding by individuals and more use of cash as a payment instrument. There is also a segment (in Focus 3) on the major changes introduced in regulations on the retail-value payment system in Colombia, as provided for in Decree 1692 of December 2020. The fourth section of this report refers to the important innovations and tech¬nological changes that have occurred in the retail-value payment system. Four themes are highlighted in this respect. The first is a key point in building the financial infrastructure for instant payments. It involves of the design and im¬plementation of overlay schemes, a technological development that allows the various participants in the payment chain to communicate openly. The result is a high degree of interoperability among the different payment service providers. The second topic explores developments in the international debate on central bank digital currency (CBDC). The purpose is to understand how it could impact the retail-value payment system and the use of cash if it were to be issued. The third topic is related to new forms of payment initiation, such as QR codes, bio¬metrics or near field communication (NFC) technology. These seemingly small changes can have a major impact on the user’s experience with the retail-value payment system. The fourth theme is the growth in payments via mobile tele¬phone and the internet. The report ends in section five with a review of two papers on applied research done at Banco de la República in 2020. The first analyzes the extent of the CRCC’s capital, acknowledging the relevant role this infrastructure has acquired in pro¬viding clearing and settlement services for various financial markets in Colom¬bia. The capital requirements defined for central counterparties in some jurisdic¬tions are explored, and the risks to be hedged are identified from the standpoint of the service these type of institutions offer to the market and those associated with their corporate activity. The CRCC’s capital levels are analyzed in light of what has been observed in the European Union’s regulations, and the conclusion is that the CRCC has a scheme of security rings very similar to those applied internationally and the extent of its capital exceeds what is stipulated in Colombian regulations, being sufficient to hedge other risks. The second study presents an algorithm used to identify and quantify the liquidity sources that CUD’s participants use under normal conditions to meet their daily obligations in the local financial market. This algorithm can be used as a tool to monitor intraday liquidity. Leonardo Villar Gómez Governor