Academic literature on the topic 'Inc National Cargo Bureau'

Background:ObjectivesThe objective of this study is to report long-term, end-of-study-program safety outcomes, relating to major adverse cardiovascular events (MACE), in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) who received ≥1 dose of Ixekizumab (IXE) over 5 years (PsO) or 3 years (PsA, axSpA).MethodsThe incidence of MACE was assessed across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA) examining long-term safety of IXE. MACE rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted incidence rates (IRs) per 100 patient-years, at successive year intervals are reported.ResultsThe incidence of MACE was low among patients with PsO (IR=0.5), PsA (IR=0.5), and axSpA (IR=0.3). In the PsO cohort, of the 103 reported MACE cases, 20 were fatal (19.4%), 57 recovered (55.3%), and 17 recovered with sequelae (16.5%). Of the 12 reported MACE cases in the PsA cohort, 2 were fatal (16.7%), 9 recovered (75.0%), and 1 recovered with sequelae (8.3%). All 6 MACE cases reported in the axSpA cohort recovered (100.0%).IRs were low and stable over the treatment periods. The most common types of MACE reported in the PsO, PsA and axSpA cohorts were non-fatal myocardial infarction (PsO: IR= 0.3; PsA: IR=0.3; axSpA: IR=0.3), nonfatal stroke (PsO: IR=0.1; PsA: IR=0.2) and vascular death (PsO: IR=0.1; PsA: IR=0.1). All MACE cases were confirmed by adjudication.ConclusionThe incidence of MACE was low and stable over the IXE treatment periods examined.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers.Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma,Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte.Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy’s Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara.Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development,LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie,Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Carlo Salvarani Consultant of: AbbVie, Eli Lilly and Company, and Roche, Grant/research support from: Roche, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai, Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Consultant of: AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck,Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Regeneron, Sun Pharma, and UCB Pharma, Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer.Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim,Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company),

Background:Patients (pts) with rheumatoid arthritis (RA) have an increased risk of some malignancies vs the general population, and this can vary by region/race.1,2 Data on the epidemiology and impact of biological (b)DMARDs and targeted synthetic (ts)DMARDs, such as Janus kinase (JAK) inhibitors, on the incidence of malignancies in Japanese pts with RA are limited. The National Database of Rheumatic Diseases in Japan (NinJa) is one of the largest RA registries in Japan.Objectives:To evaluate the incidence of malignancies in Japanese pts with RA using NinJa registry data.Methods:This retrospective observational study analysed NinJa registry data for Japanese pts with RA aged ≥18 years with ≥1 data entry between 2013 (first JAK inhibitor approval for RA in Japan) and 2018. The overall cohort included all pts with RA, and two sub-cohorts were analysed: pts exposed and unexposed to bDMARDs (exposure defined as ≥1 bDMARD reported in database). Crude incidence rates (IRs) for malignancies (including non-melanoma skin cancer) were calculated as the number of events per 100 pt-years of follow-up (time between start of follow-up or the date of first bDMARD exposure [for bDMARD-exposed pts] and end of observation period, or withdrawal from database). The most recent data for incidence of malignancy in the Japanese general population (2013–2017 data from the National Cancer Center, Japan) were used to calculate standardised incidence ratios (SIRs) and age- and sex-adjusted standardised rates (ASRs) for malignancies. Cross-sectional (per calendar year) and cumulative analyses were performed for the overall cohort. Cumulative rates were calculated for sub-cohorts, and all cumulative analyses were repeated excluding pts exposed to JAK inhibitors (ie ≥1 JAK inhibitor reported in database).Results:Data were collected for 26 607 Japanese pts with RA from 2013–2018. In the cross-sectional analysis (Table 1), the SIR and ASR for malignancies in all pts with RA were generally consistent from 2013–2018. In the cumulative analysis, the SIR (95% CI) for malignancies from 2013–2018 was 0.97 (0.91, 1.03) in all pts with RA, and 0.93 (0.82, 1.04) and 0.99 (0.92, 1.07) in pts exposed and unexposed to bDMARDs, respectively (Figure 1). Adjusting for age/sex, the cumulative ASR (95% CI) for malignancies from 2013–2018 was 0.83 (0.76, 0.90) in all pts with RA, and 0.82 (0.69, 0.95) and 0.86 (0.77, 0.96) in pts exposed and unexposed to bDMARDs, respectively (Figure 1). In all cohorts, the cumulative SIR and ASR were similar when pts exposed to JAK inhibitors were excluded (Figure 1).Table 1.Cross-sectional analysis of the incidence of malignancies in Japanese pts with RA from 2013–2018All RA2013 (N=13 423)2014 (N=15 584)2015 (N=15 751)2016 (N=16 107)2017 (N=15 994)2018(N=15 003)Total follow-up, PY13 35314 86614 82914 97014 74814 898Pts with events, n140164174168161211Crude IRa(95% CI)1.05(0.89, 1.24)1.10(0.95, 1.29)1.17(1.01, 1.36)1.12(0.97, 1.31)1.09(0.94, 1.27)1.42(1.24, 1.62)ASRa,b(95% CI)0.76(0.60, 0.93)0.76(0.62, 0.90)0.90(0.68, 1.11)0.88(0.68, 1.07)0.80(0.62, 0.98)0.88(0.74, 1.01)SIRb(95% CI)0.97(0.82, 1.14)1.01(0.86, 1.17)1.02(0.87, 1.18)0.88(0.75, 1.02)0.86(0.73, 1.00)1.10(0.95, 1.25)aIR/ASR were calculated as number of events per 100 PY of follow-upbData from a Japanese general population database of malignancy incidence from 2013–2017, provided by the Center for Cancer Control and Information Services, National Cancer Center, JapanPY, pt-yearsConclusion:The incidence of malignancies in Japanese pts with RA, registered in the NinJa database from 2013–2018, was similar to that in the Japanese general population. The SIR and ASR for malignancies were comparable in pts exposed and unexposed to bDMARDs. In all cohorts, rates did not increase when pts exposed to JAK inhibitors were included.References:[1] Dougados et al. Ann Rheum Dis 2014; 73: 62-68.[2] Parikh-Patel et al. Cancer Causes Control 2009; 20: 1001-1010.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Toshihiro Matsui Speakers bureau: Astellas, Ayumi, Chugai, Daiichi-Sankyo, Eli Lilly, Ono, Pfizer Inc, Takeda, Tanabe-Mitsubishi, Consultant of: Pfizer Inc, Grant/research support from: Chugai, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shigeyuki Toyoizumi Employee of: Pfizer R&D Japan, Fujio Matsuyama Consultant of: Pfizer Inc, Employee of: CRECON Medical Assessment Inc, Tatsunori Murata Consultant of: Pfizer Inc, Employee of: CRECON Medical Assessment Inc, Yukitomo Urata Speakers bureau: Asahi Kasei, Chugai, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Asahi Kasei, Chugai, Pfizer Inc, Kimito Kawahata Speakers bureau: Pfizer Inc, Consultant of: Pfizer Inc, Grant/research support from: Pfizer Inc, Shigeto Tohma Speakers bureau: Astellas, Ayumi, Chugai, Ono, Pfizer Inc, Takeda, Consultant of: Pfizer Inc

Abstract INTRODUCTION: Despite proteasome inhibitors (PIs) improving multiple MM (MM) outcomes, patients often become resistant. Identifying mechanisms of resistance with translational potential are an urgent unmet clinical need. Preliminary studies from our group have identified that the therapeutically targetable acid ceramidase, ASAH1, is a key mediator of PI resistance and its presence in extracellular vesicles (EVs) derived from resistant MM cells, confers PI resistance on drug naïve MM cells. METHODS: Nanosight technology, transmission electron microscopy and immunoblot were used to define EVs. Viability and apoptosis assays were used to determine the effects of EVs and inhibitors on resistance acquisition/sensitization to PIs. LC-MS was used to interrogate EV cargo contents. Clinical relevance of ASAH1 was determined in multiple human data cohorts (M2GEN and MMRF CoMMpass). Genetic (shRNA) and pharmacological (ceranib-2) approaches were used to assess the role of ASAH1 mechanistically in vitro and in vivo using multiple isogenic naïve and PI resistant cell lines, patient derived CD138+ MM cells and NSG mouse models. RESULTS: Co-culture of sensitive MM cells with resistant MM-EVs alone significantly protected against PI cytotoxicity. Proteomic profiling revealed high levels of ASAH1 in EVs derived from PI resistant MM cells. Further, we observed ASAH1 is abundant in lysates of multiple PI resistant cell lines compared to their isogenic drug sensitive counterparts. In human datasets, high ASAH1 expression was noted in PI resistant MM patients compared to those newly diagnosed and correlated with significantly shorter survival times. Mechanistically, knockdown of ASAH1 led to reduced conversion of ceramide to sphingosine 1-phosphate (S1-P) and decreased expression/activity of the anti-apoptotic proteins MCL-1, BCL2 and BCL-xL and increases in pro-apoptotic BIM and NOXA. Notably, ASAH1 knockdown also significantly sensitized the cells to PI treatment and this effect was rescued by addition of exogenous S1-P. Pharmacological inhibition of ASAH1 with ceranib-2 also sensitized resistant cells to PI treatment and prevented EV mediated resistance transfer in vitro. This was recapitulated ex vivo with human clinical samples. Our orthotopic in vivo model using PI-resistant U266-PSR cells show that ceranib-2 is highly effective in limiting the growth of PI-resistant disease, protecting against MM induced bone disease, and increasing overall survival compared to both bortezomib and vehicle controls. CONCLUSION: We define the ceramidase ASAH1 as a novel, druggable target for the treatment of PI resistant MM. Disclosures Hampton: M2Gen: Current Employment. Siqueira Silva: AbbVie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Research Funding. Shain: Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Genzyme: Consultancy, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a viable treatment option for many cancers but its clinical utility is limited due to the occurrence of graft-versus-host disease (GVHD). Understanding the impact of obesity on immune function has become increasingly important in the setting of the current obesity pandemic. We report here that obesity has a negative and selective impact on acute gut GVHD. Diet-induced obese (DIO) mice exhibited increased gut permeability, endotoxin translocation and radiation-induced gastrointestinal damage. After allo-HSCT, DIO recipients across strains and sex had markedly increased pro-inflammatory cytokines (IL-6, TNF), GVHD biomarker ST2, MHC class II expression and exhibited rapid mortality associated with severe acute gut pathology. This obesity-associated lethal acute gut GVHD was dependent on donor CD4 T cells and occurred even in minor MHC mismatch strain combination in which only a delayed skin chronic GVHD resulted in lean recipients. Pro-inflammatory cytokine blockade targeting both IL-6 and TNF ameliorated obesity-associated acute gut GVHD while maintaining graft-versus-tumor (GVT) effects. Microbiome assessment of DIO mice revealed markedly reduced microbiome diversity and decreased Clostridiaceae abundance. Additionally, DIO mice had a significant increase of GVHD-associated Akkermansia muciniphila before and after allo-HSCT compared to the controls. Extended antibiotic treatment of DIO mice protected from the endotoxin translocation, cytokine storm as well as gut GVHD pathology but did not protect later development of chronic skin GVHD. These results demonstrate that obesity alters the microbiome and imparts differential effects on GVHD following allo-HSCT with decreased survival and this inferior outcome can be pre-empted by combined pro-inflammatory cytokine blockade or antibiotic pretreatment. Disclosures Pai: Roche-Genentech: Employment. Holtan:CSL Behring: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy. Ferrara:ViraCor: Consultancy; Incyte: Consultancy; Kamada: Consultancy; Mallinckrodt: Consultancy; Enlivex: Consultancy; Xenikos: Consultancy; CSL Behring: Consultancy; National Institutes of Health: Research Funding. Levine:Novartis: Honoraria; Kamada: Research Funding; bluebird bio: Consultancy; National Cancer Institute: Research Funding; Incyte: Consultancy, Research Funding; Ironwood: Honoraria; Biogen: Other: non-financial support; Viracor: Patents & Royalties: biomarker patent. Abedi:Abbie: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau; Takeda: Speakers Bureau. Blazar:Kamon Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Five Prime Therapeutics Inc: Co-Founder, Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics and BlueRock Therapeuetics: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc.: Research Funding; RXi Pharmaceuticals: Research Funding; Alpine Immune Sciences, Inc.: Research Funding; Abbvie Inc: Research Funding; Leukemia and Lymphoma Society: Research Funding; Childrens' Cancer Research Fund: Research Funding; KidsFirst Fund: Research Funding; Tmunity: Other: Co-Founder; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees.

This paper selects the relevant data of 30 years from 1989 to 2018 from the National Bureau of Statistics. This paper selects the gross national income as the focus variable, and the number of business outlets, cargo transportation volume, investment in fixed assets and the total population of the country as the control variables to make an empirical analysis on the influencing factors of express delivery volume in China. EVIEWS software is used to estimate, test and correct the parameters of the model. The economic significance of the final results is analyzed, and then the research conclusion is drawn and the existing deficiencies are summarized.

Abstract Introduction: There are some treatment options for lower risk myelodysplastic syndromes (MDS) such as erythropoiesis-stimulating agents (ESAs), anabolic steroids, hypomethylating agents, and immunosuppressants. The object of this multicenter retrospective study was to survey the current situation about treatment selection and the prognosis of the lower risk MDS cases in Japan. We also evaluated the prognosis of the cases with paroxysmal nocturnal hemoglobinuria (PNH) type cells and therapeutic effects of cyclosporine. Methods: We investigated the clinical information in the form of a questionnaire for joint research facilities as to each case of newly diagnosed MDS between 2013 and 2018 corresponding to the lower risk of International Prognostic Scoring System (IPSS) or revised IPSS (IPSS-R). The diagnosis of MDS was based on WHO 2008 or WHO 2016 classification. Survival analysis was conducted using Kaplan-Meier method and log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. This study was approved by the institutional review board of the University of Tokyo and other research facilities. This work was supported by the Research Program of Intractable Disease (the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes) provided by the Ministry of Health, Labor, and Welfare of Japan. Results: 1,304 cases at thirty facilities nationwide were enrolled. Median age was 76 years [IQR, 68 - 83], and male and female ratio was 61.3% and 38.7%. At diagnosis, 19.0% and 4.4% of the cases were dependent on red blood cells and platelets transfusion, respectively. The risk classification of enrolled cases was as follows: very low, 217 (16.6%); low, 652 (50.0%); intermediate, 360 (27.6%); high, 56 (4.3%); very high, 4 (0.3%); not determined, 14 (1.1%). 1,230 cases of the very low, low and intermediate risk groups were included in subsequent analyzes. Serum erythropoietin levels were measured in 466 cases (37.9%) with a median of 61.8 IU/l, and 74.2% and 85.7% cases showed less than 200 IU/l and 500 IU/l, respectively. PNH type cells in the peripheral blood were evaluated in 231 cases and were positive in 33 cases (14.3%). Median follow-up period was 22 months. As an initial therapy, 26.4% and 11.6% of transfusion-dependent and independent cases started to receive ESAs, respectively. 16.6% and 11.5% took oral anabolic hormones, and azacytidine were administered to 17.0% and 7.2% of each group. 55.4% of transfusion-independent cases were just followed up at first. Median overall and acute myeloid leukemia (AML)-free survival was 70.0 months [95% CI, 61.0 - not reached] and 62.0 months [95% CI, 54.0 - 74.0], respectively. Log-rank analysis revealed significant differences among IPSS-R risk groups about overall and AML-free survival (p<0.01 and p<0.01, respectively). Multivariate analysis confirmed that initiating azacytidine at the time of diagnosis conferred an independent significant poor prognostic factor with respect to overall survival (hazard ratio for death, 1.74; p<0.01) and AML-free survival (hazard ratio for death or onset of AML, 1.86; p<0.01) in addition to sex, age, IPSS-R classification, and transfusion-dependency. Comparing thirty-three positive cases of PNH type cells with 198 negative cases, overall and AML-free survival was significantly better in the former group (p<0.01 and p<0.01, respectively). Median overall and AML-free survival were not reached in the positive group and 51.0 months [95% CI, 47.0 - 79.0] and 49.1 months [95% CI, 40.0 - 57.1] in the negative group, respectively. Interestingly, focused on the positive cases, 14 cases receiving cyclosporine revealed better AML-free survival than the others (p=0.033). Overall survival was tended to be better (p=0.052). On the other hand, cyclosporine did not improve the prognosis of the PNH type cells negative cases. It is thought to be consistent with the effectiveness of immunosuppressive therapy in aplastic anemia with PNH type cells. Conclusion: ESAs, anabolic steroids, and azacytidine were frequently selected as an initial treatment for lower risk MDS cases in Japan, however, when to start azacytidine is an issue for consideration. Good response to cyclosporine may be obtained in cases with PNH type cells. Disclosures Masamoto: Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; MSD K.K.: Speakers Bureau. Miyazaki: Kyowa-Kirin: Honoraria; Sumitomo-Dainippon: Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Astellas: Honoraria; Janssen: Honoraria; Eisai: Honoraria; Daiichi-Sankyo: Honoraria; Chugai: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Mitani: Nippon Shinyaku Co.: Research Funding, Speakers Bureau; MSD Pharma.: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Pfizer Inc.: Speakers Bureau; Celgene Co.: Speakers Bureau; Takeda Pharma.: Research Funding, Speakers Bureau; Kyowa Kirin,: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Shire plc: Speakers Bureau; BML Inc: Speakers Bureau; Mochida Parma.: Speakers Bureau; Alexion Pharma.: Speakers Bureau; AbbVie Inc.: Speakers Bureau; Ono Pharma.: Speakers Bureau; Chugai Pharma.: Research Funding; Teijin Pharma.: Research Funding; Sumitomo Dainippon Pharma: Research Funding; Taiho Phama.: Research Funding; Otsuka Pharma.: Research Funding. Kurokawa: Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; MSD K.K.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau.

The study assessed the performance of public sector funded infrastructure in Nigeria, with a special focus on airports. It utilized secondary data obtained from the Federal Airports Authority of Nigeria (FAAN), the Nigerian Civil Aviation Authority (NCAA), and the National Bureau of Statistics (NBS) covering the period 2004 to 2016. A simple regression analyses of the data were carried out using total number of employees as the predictor variable and the total aircraft movement, total passenger movement, and total cargo movement as the dependent variables. The results of the analyses show that the p values calculated were < 0.05 alpha value, implying existence of a statistical relationship among the dependent variables (aircraft movement, passenger throughput, and cargo throughput) and independent variable (number of employees). Furthermore, the time series graphs show fluctuations in growth of the outputs (passenger throughput, aircraft movement and cargo throughput) for the Nigerian air transport system at various periods. This study has shown that there is a need for the government and stakeholders to take immediate actions in tackling factors responsible for the decline and fluctuations in the air transport industry.

The study investigated the relationships between the poverty level in Nigeria and levels of global and local pirate attacks against ships on one hand; and between the unemployment rate in Nigeria and the level of local and global attack against ships, as well as the volume of cargo pilfered from Nigerian ports, on the other hand. The study employed secondary data sourced from the Nigerian Ports Authority, the National Bureau for Statistics (NBS), and the International Maritime Bureau (IMB) on the poverty rate, unemployment rate, levels of pirate attacks against ships in local and global waters, and volume of cargo pilferages in ports. The multiple regression analysis method was used to analyze the dataset obtained, using poverty rate and unemployment rate as the dependent variables in each case. It was found that poverty among dwellers is a component driver of maritime piracy and sea robbery against ships trading in Nigeria, since there is a significant relationship between the level of maritime insecurity and the rate of poverty in Nigeria. The study also found that there is a significant relationship between the level of maritime piracy/sea robbery and the unemployment rate in Nigeria. Highlights Maritime insecurity in Nigeria waterways Pirate attacks against ships trading in Nigeria waters is linked to unrest in the Niger Delta region of Nigeria Maritime piracy in Nigeria waters is correlated with Poverty, unemployment, economic hardship in Nigeria Significant relationship exist between maritime insecurity and poverty rate in Nigeria

Background: Improved therapeutic strategies for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) remain an unmet need. Venetoclax (Ven), a potent, highly selective, oral B-cell lymphoma 2 (BCL-2) inhibitor, and navitoclax (Nav), an oral BCL-2, BCL-XL, and BCL-W inhibitor, directly bind their BCL-2 family member targets to promote apoptosis. Ven and Nav have shown synergistic antileukemic effects in ALL preclinical models, suggesting dependence on BCL-2 family members. The addition of Ven to low-dose Nav may potentiate efficacy without the dose-limiting thrombocytopenia associated with Nav monotherapy (J Clin Oncol. 2012;30:488). Ven in combination with Nav and chemotherapy are under investigation in a Phase 1, multicenter, open-label, dose-escalation study in patients with R/R ALL and LL (NCT03181126). The results of a previous report on the overall study population (adult and pediatric patients) showed the triplet combination was well tolerated, with promising response rates observed (Jabbour, et al. EHA 2020. Abstract 2389). For the first time, reported here are safety, tolerability, pharmacokinetics, and antitumor activity of Ven with Nav and chemotherapy among the pediatric patients treated in that Phase 1 study. Methods: Eligible pediatric patients (aged ≥4-&lt;18 years and weight ≥20 kg) with R/R ALL and LL were enrolled to receive 400 mg Ven (weight-adjusted equivalent) daily. Nav was administered daily at 3 dose levels (25, 50, 100 mg) for patients weighing ≥45 kg and 2 dose levels (25, 50 mg) for patients weighing &lt;45 kg. Dose escalation decisions were guided by Bayesian optimal interval design. Patients could receive chemotherapy (PEG-asparaginase, vincristine, and dexamethasone) at the investigator's discretion. Primary outcome measures included safety assessments and pharmacokinetics. Secondary outcome measures included efficacy assessments. Exploratory biomarker assessments included evaluation of minimal residual disease (MRD). A safety expansion cohort assessed a discontinuous dosing schedule, 21 days on and 7 days off, of Ven with 50 mg Nav (25 mg for patients weighing &lt;45 kg). Results: As of June 23, 2020, 18 pediatric patients (pts) have enrolled (12 in dose-escalation; 6 in safety expansion); 13, 3, and 2 pts had B-ALL, T-ALL, and LL, respectively. Among pts in the dose-escalation phase, 6 received 25 mg Nav and 6 received 50 mg. Median age was 10 years (range, 6-16 years), 56% of pts were male, and the median number of prior therapies was 2 (range, 1-6). Median time on study was 10.4 months. All pediatric pts experienced treatment-emergent adverse events (TEAEs), and the most common were febrile neutropenia (50%), vomiting (44%), hyperglycemia (39%), and hypokalemia (39%). Grade 3/4 TEAEs occurred in 89% of pediatric pts, and the most common were febrile neutropenia (50%), neutropenia (33%), thrombocytopenia (33%), and anemia (28%). The only Grade 3/4 nonhematologic TEAEs related to Ven or Nav that occurred in &gt;1 pediatric pt were alanine aminotransferase increased (n=2) and vomiting (n=2). Of 8 dose-limiting toxicities (DLTs), 2 occurred in pediatric pts. The 2 DLTs included delayed count recovery (25 mg Nav) and sepsis (50 mg Nav, occurred after database lock). No pediatric pts experienced tumor lysis syndrome. No Grade 5 TEAEs occurred in pediatric pts; 8 pediatric pts (44%) died from disease progression. Ten pediatric pts (56%) achieved complete response (CR)/CR incomplete recovery (CRi)/CR without platelet recovery (CRp); 7 pts (39%) achieved undetectable MRD. Median overall survival was 11.4 months (95% CI, 2.9 months-not estimable). Eight pts (44%) proceeded to transplantation (n=5) or CAR T-cell therapy (n=3; cells harvested before start of study; Figure). Weight-based dosing of Ven and Nav achieved comparable exposures in pediatric pts. Exploratory correlative biomarker analyses, including BH3 profiling and genomic analyses, are underway and will be presented. Conclusion: In this Phase 1 study, Ven with Nav and chemotherapy was well tolerated and had promising efficacy in heavily pretreated pediatric patients with ALL and LL. Given that there were four DLTs with 100 mg Nav without evidence of increased efficacy, the recommended Phase 2 dose for adult and pediatric patients is 400 mg Ven with 50 mg Nav for patients weighing ≥45 kg and 25 mg Nav for patients weighing &lt;45 kg. Figure Disclosures Rubnitz: AbbVie Inc.: Research Funding. Alexander:Abbvie, Inc.: Other: Travel Support. Laetsch:Bayer: Consultancy, Research Funding; Cellectis: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Research Funding. Khaw:Amgen: Other: Travel Support, Research Funding; Novartis: Other: Travel Support; AbbVie, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Jazz Pharmaceuticals: Research Funding; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: recipient of a share in royalty payments . Pullarkat:Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Opferman:St. Jude Children's Research Hospital: Current Employment; AbbVie, Inc.: Research Funding; National Institutes of Health: Research Funding. Rosenwinkel:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Tong:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Pesko:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Badawi:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Vishwamitra:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Kim:AbbVie, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: may hold stock or other options. Mullighan:Illumina: Consultancy, Honoraria, Speakers Bureau; AbbVie, Inc.: Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau. OffLabel Disclosure: Yes, venetoclax is a BCL-2 inhibitor that is FDA approved for some indications. Venetoclax for treatment of acute lymphoblastic leukemia is not an approved indication.

Abstract Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the world and has a median age at diagnosis in the seventh decade. FL in young adults (YA; 40 years old or younger) is extremely rare. Currently, there are no standard approaches guiding treatment of YA patients with FL, and very little is known about disease characteristics and outcomes of YA patients with FL given limited research conducted in this vulnerable population. To gain further insight into FL in YA, we analyzed the National LymphoCare Study (NLCS) to describe disease and patient characteristics, as well as features of treatment in YA patients with FL. We previously reported that 2-year progression-free survival (PFS) is an important survival endpoint in patients with FL undergoing chemo-immunotherapy. Hence, we also sought to characterize 2-year PFS in this age group and compare it to older cohorts. Methods: Evaluablepatients were identified in the NLCS, and those between 18–40 years of age with newly diagnosed FL at any stage were classified as YA patients. Patients with mixed histology or transformed disease were excluded, as were patients with progression of disease prior to beginning first-line treatment. Survival probability was estimated by the Kaplan-Meier method. We estimated the association of age group with PFS using hazard ratios (HR) and 95% confidence intervals (CI) from multivariable Cox models. Results: A total of164 YA patients with FL were analyzed, representing 6.2% of the NLCS population, similar to the observed frequency in the Surveillance, Epidemiology, and End Results (SEER) Program data (4.8% of all FL). Sixty nine percent of YA patients had advanced stage disease. The majority of patients (80%) had low-grade histology, and 50% had good risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent of patients (31/164) underwent watchful waiting, 12% received rituximab monotherapy, and 47% received chemo-immunotherapy (61% of whom received R-CHOP [rituximab, doxorubicin, vincristine, prednisone]). There was no significant difference in FLIPI score or other baseline disease characteristics compared to adult patients aged 41–60 years. Eleven deaths occurred among YA with FL; only 5 of these were lymphoma related. Overall survival (OS) at 2 years was 97.4% (95% CI 93.3%, 99.0%), and at 5 years, 93.7% (88.3%, 96.7%), which was similar to patients aged 41–60 (97.2% [96.0%, 98.0%] at 2 years, and 92.0% [90.1%, 93.5%] at 5 years). After a median follow-up of 7.1 years, OS in YA FL was 92%. Through follow-up, there were 64 PFS events. The estimated 2-year PFS (95% CI) for YA and adults 41–60 was 75.9% (67.1%, 82.6%) and 80.9% (78.1%, 83.4%), respectively. After adjusting for FLIPI score, there was no difference in PFS for YA with FL requiring first-line treatment (excluding watchful waiting) compared to adults aged 41–60 years (HR=0.93; 95% CI 0.69, 1.25), and no difference in OS compared to adults aged 41–60 years (HR=1.19; 95% CI 0.64, 2.23). Conclusions: In the largest cohort of YA patients with FL to date, we found few differences in outcomes compared to patients aged 41–60. FLIPI and other disease characteristics were similar to adults aged 41–60 years. There were no differences between YA FL and adults aged 41–60 in PFS for all treated patients. OS in the YA group of patients with FL was outstanding. YA patients with FL have reassuringly similar outcomes to patients aged 41–60. Fertility preservation and survivorship issues should be taken into consideration when defining management strategies, but otherwise these data support that YA patients with FL should not be approached differently from older adults with the same disease. Disclosures Byrtek: Genentech, Inc.: Employment, Equity Ownership. Dawson:Genentech, Inc.: Employment, Equity Ownership. Zhou:RTI-HS: Employee of RTI-HS, which has research contracts with Genentech Other. Flowers:Seattle Genetics: Consultancy; Spectrum: Consultancy, Research Funding; Sanofi: Research Funding; Abbott: Research Funding; Novartis: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Allos: Consultancy. Farber:Gilead: Speakers Bureau; Janssen/Pharmacyclics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Leukemia Lymphoma Society NJ Chapter: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Speakers Bureau, Stock ownership Other. Cerhan:Genentech, Inc.: LymphoCare Scientific Advisory Board Other. Link:Genentech, Inc.: Consultancy, Scientific Advisory Board for Genentech Other.

Abstract Three new industry standards, American National Standard/Scaffold & Access Industry Association, Inc. (ANSI/SAIA) A92.20, A92.22 and A92.24, were introduced in December 2018 to address the safe design, use and training associated with mobile elevating work platforms (MEWPs). MEWPs are defined in the new Standards as “machine/device intended for moving persons, tools and material to working positions, consisting of at least a work platform with controls, an extending structure and a chassis.”2 This definition encompasses certain types and sizes of MEWPs such as scissor lifts, articulating boom lifts, telescopic boom lifts and straight mast boom lifts. Replacing product-specific industry standards, these three new Standards significantly change the design, testing, rental, use and training requirements associated with MEWPs. The Standards also offer greater clarity to the assigned responsibilities associated with these functions to various entities including manufacturer, dealer, owner, user, supervisors, operator, occupants, lessor, lessee and brokers. Compliance with these voluntary standards became effective June 1, 2020.3 Recognized hazards associated with MEWPs include: tip overs associated with wind loads and contact with other obstacles, contact with power lines leading to electrocutions, caught-between the lift and other objects, falls from platform and equipment collapse.4 This effort will analyze injury data including both fatal and nonfatal incidents associated with MEWPs to better understand the trends and quantifying many of the risks associated with the operation and maintenance of MEWPs. Injury data from the U.S. Bureau of Labor and Statistics (BLS) will be reviewed. The effort will also identify and explore how the design, use and training requirements introduced in the new industry standards address the hazards and risk associated with MEWPs.