Journal articles on the topic 'Ley 26061'

El presente artículo tiene como objetivo analizar las causas y antecedentes que han contribuido a que, en Argentina, la designación del Defensor del Niño se haya judicializado. En el fallo caratulado “Fundación Sur Argentina y otros c/en Honorable Cámara de Senadores de la Nación y otro s/Amparo ley 16.986”, (expediente N° 15581/2015), publicado el 9 de marzo de 2017, el Juzgado Nacional de Primera Instancia en lo Contencioso Administrativo Federal Número 3, exhortó al Congreso de la Nación, debido a su dilación, a designar un Defensor del Niño para dar cumplimiento a lo establecido en la ley 26.061.

Background. Transfection efficacy after nonviral gene transfer in primary epithelial cells is limited. The aim of this study was to compare transfection efficacy of the recently available method of nucleofection with the established transfection reagent FuGENE6.Methods. Primary human keratinocytes (HKC), primary human fibroblasts (HFB), and a human keratinocyte cell line (HaCaT) were transfected with reporter gene construct by FuGENE6 or Amaxa Nucleofector device. At corresponding time points,β-galactosidase expression, cell proliferation (MTT-Test), transduction efficiency (X-gal staining), cell morphology, and cytotoxicity (CASY) were determined.Results. Transgene expression after nucleofection was significantly higher in HKC and HFB and detected earlier (3 h vs. 24 h) than in FuGENE6. After lipofection80%–90%of the cells remained proliferative without any influence on cell morphology. In contrast, nucleofection led to a decrease in keratinocyte cell size, with only20%–42%proliferative cells.Conclusion. Related to the method-dependent increase of cytotoxicity, transgene expression after nucleofection was earlier and higher than after lipofection.

In this study, the appropriate input parameters for achieving minimum surface roughness and high material removal rate are selected for wire electrical discharge machining of cold-work steel 2601. Mathematical modeling acquired by experimental result analysis is used to find the relation between input parameters including electrical current, gap voltage, open-circuit voltage and pulse-off time and output parameters. Subsequently, with exploitation of variance analysis, importance and effective percentages of each parameter are studied. The combination of optimum machining parameters is acquired using the analysis of ratios of signal-to-noise. Finally, according to multiple-objective optimization, outputs acquired from Non-dominated Sorting Genetic Algorithm led in achieving appropriate models. The optimization results showed suggested method has a high performance in problem solving.

Abstract The Motuo fault (MTF) strikes along the Yarlung Zangbo suture zone on the eastern boundary of the Namche Barwa syntaxis. The movement pattern and Quaternary activity of the MTF remain unclear, which hampers efforts to undertake meaningful seismic hazard assessments near the southeastern part of the Tibetan plateau and to understand the tectonic evolution of the Namche Barwa syntaxis. In this study, the MTF is shown to feature left-lateral strike-slip movements with offset gullies and mountain ridges and appears to have ruptured during the late Pleistocene to Holocene, as evidenced from geological, paleoseismic, and radiocarbon dating investigations. Specifically, at least three surface-rupturing paleoseismic events are revealed; two events occurred after 2606 B.P. and after 18.2 ka. Combining this information with previous Global Positioning System results in southeastern Tibet, we suggest that, as a boundary fault, the MTF regulates the movements of the Namche Barwa and Chayu blocks. The velocity difference between the two blocks advancing to the north is the main mechanism of left-lateral strike-slip motion along the MTF. The accumulation and release of shear stress between the two blocks have led to strong activity along the MTF, since the late Quaternary.

Introduction: Rupture of a Quadriceps Tendon (QT) following a Total Knee Arthroplasty (TKA) is a rare complication. The purpose of this study was to report outcomes and complications of QT repair following TKA. Methods: From a cohort of 437 QT repairs, 19 individuals were identified who had previously undergone a TKA on the ipsilateral leg. Data was collected on individuals with a minimum follow up of 3 months post QT repair (n=16), including Knee Society Scores, pre and post-operative lag, and pre and post-operative range of motion. Results: 13 patients were treated with End-to-End (EE) repairs and 6 were treated with transosseous or suture anchor repair (ATO). In the ATO group, there was no difference in pre (68.0 ± 22.5) and post KSS (82 ± 9.16) (p=0.231), but in the EE group, there was a significant improvement in KSS (pre=67.8 ± 13.1, post=86 ± 16.75, p=0.0027). There was significant difference in post-operative extension lag between ATO (26.0 ± 12.6) vs. EE (4.0 ± 2.74) (p=0.0083). Four out of six ATO patients had extension lag ≥10 degree extensor lag (66.7%) compared to 2 out of 13 (15.4%) patients in the EE group. Compared to EE, ATO repair had an 8.00 times odds of re-tear (95% CI: 0.53,120.6; p=0.133) and 2.75 times greater risk of infection (95% CI: 0.284, 26.61; p=0.382). Conclusion: Patients who underwent EE repair had better functional improvements compared to the ATO group and smaller extension lag.

Background: Similarities between the pathobiology of aortic stenosis (AS) and atherosclerosis have led to the concept that pharmacological strategies effective in atherosclerosis might attenuate valvular inflammation. Objective: The objective of this study was to assess how angiotensin-converting enzyme inhibitors (ACEIs) might affect valvular expression of coagulation and inflammatory proteins in AS. Material/Methods: We studied 111 advanced AS patients (62 males, aged 63.3±11.2 years) undergoing valve replacement. Plasma levels, valvular expression and mRNA transcripts of tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, along with C-reactive protein (CRP) and interleukin-6 (IL-6) were evaluated. Results: TF-, TFPI-, CRP and prothrombin valvular expression was not related to demographics, concomitant diseases or plasma TF, free-TFPI or IL-6. ACEIs-treated patients (n=37), mainly due to hypertension (n=24, 65%), showed decreased areas for valvular TF (13.64±6.43 vs. 18.05±6.81%, p=0.03), TFPI (32.6±7.8 vs. 49.15±9.5%, p<0.001), prothrombin (23.47±1.93 vs. 26.61±1.4%, p<0.001), CRP (0.75 [0-9] vs. 1.4 [0-8]%, p=0.009), and IL-6 (3.2±0.65 vs. 6.4±1.83%, p<0.001) compared with non-ACEIs patients. Similarly, patients treated with ACEIs showed lower mRNA expression of TF (1.22±0.47 vs. 2.27±1.42, p=0.041), prothrombin (0.13±0.07 vs. 0.81±0.37, p<0.001), CRP (0.73±0.29 vs. 1.25±0.69, p=0.04), and IL-6 (7.6±5.16 vs. 13.67±7.3, p=0.046). Conclusions: In patients with severe AS, ACEIs use is associated with lower expression of valvular proteins involved in coagulation and inflammation, thus ACEIs therapy could be important in altering atherosclerosis-like processes within stenotic aortic valves.

Polycythemia vera (PV) is an acquired, clonal stem cell, myeloproliferative, hematological disorder with variable increase in erythrocytes, neutrophils and granulocytes. PV causes significant morbidity and mortality from thrombotic and hemorrhagic complications and has a propensity for leukemic transformation. Phlebotomy, interferon a and myelosuppressive chemotherapy have been the cornerstones of treatment to date. With no specific drugs to treat PV effectively, the development of new therapeutic modalities is important. A somatic mutation in the JAK2 tyrosine kinase (V617F) causing constitutive activation of the JAK/STAT pathway was recently reported in over 80% of PV patients. Based on this observation, we explored the therapeutic efficacy of tyrosine kinase inhibitors (TKIs) such as imatinib (Gaikwad A et al, Blood106: 2601, 2005) and AMN107 for PV. These TKIs showed marginal efficacy in vitro. Research using natural sources has led to important pharmacological targets for cancer therapy. Several plant molecules have either been introduced to the US market or are in late-phase clinical trials. We focused on a natural product called “Avicin D,” which is a plant derived triterpene electrophilic molecule with cyto-protective and anti-inflammatory functions (Haridas V et al, J. Clin. Invest113: 65, 2004; Haridas V et al, PNAS, 98:11557, 2001). Avicin D is reported to initiate selective pro-apoptotic activity in malignant cells (Mujoo K, et al. Cancer Res.61: 5486, 2001) by direct perturbation of mitochondria (Haridas V, et al. PNAS, 98: 5821, 2001). It has also been shown to down-regulate a group of pro-survival, anti-apoptotic proteins that act downstream of cytochrome c release, including HSP70, HSP90 and XIAP (Gaikwad A, et al. Clin. Cancer Res. 11: 1953Gaikwad A, et al. Clin. Cancer Res. 11: 2005). In addition, Avicin D also blocks glycolysis, a key metabolic process that malignant cells exploit for their proliferation and survival (Warburg phenomenon). To examine Avicin D’s therapeutic efficacy for PV, we utilized mouse reporter cells expressing the JAK2 V617F protein. Avicin D inhibited the growth of these cells with an IC50 of 2μM. Interestingly, in cells carrying wild-type JAK2 there was no significant inhibitory effect. In addition, Avicin D showed marked growth inhibition of human erythroleukemic cells (HEL) that harbor the JAK2 V617F mutation at an IC50 of 2μM. We then examined Avicin D’s effect on in vitro expanded native human erythroid progenitor cells. Avicin D showed specific growth inhibition of erythroid progenitor cells from PV patients (IC50 ~3μM) with no significant effect on the normal progenitors. We conclude that Avicin D should be a promising candidate for clinical trials of PV and other disorders that are associated with JAK2 V617F somatic mutations.

Resumo: O objetivo deste trabalho é colocar em relação o ensino da filosofia com um problema específico da infância: o fato de que esta apareça como um território inacessível para muitas crianças, por causa de sua identidade de gênero. Neste sentido, tento traçar aqui um mapa da infância segundo as disposições das organizações internacionais e as legislações locais argentinas que se ocupam de protegê-la, para contrastar com a realidade das crianças transgêneros, segundo algumas pesquisas realizadas por diferentes organizações. Essa comparação mostra até que ponto o mapa difere do território e nos permite perguntar pelas causas desta divergência. Falarei aqui da construção social e cultural de uma ontologia da monstruosidade para o caso destas crianças. Esta ontologia coloca um desafio no momento de pensar filosoficamente o ensino da filosofia, pois esta disciplina elabora suas reflexões e pesquisas partindo de um sujeito cujas experiências e problemas pressupõem uma certa “normalidade” em relação a qual as crianças trans estão excluídas. Palavras-chave: Identidade de género. Infância. Ontologia da monstruosidade. Ensino da filosofia. Resumen: El objetivo de este trabajo es poner en relación la enseñanza de la filosofía con un problema específico de la infancia: el hecho de que ésta aparezca como un territorio inaccesible para muchos niños y niñas, a causa de su identidad de género. En este sentido, intento trazar aquí un mapa de la infancia según las disposiciones de los organismos internacionales y las legislaciones locales argentinas que se ocupan de protegerla, para contrastar con la realidad de los niños y niñas transgénero, según algunos relevamientos realizados por diferentes organizaciones. Esa comparación muestra hasta qué punto el mapa difiere del territorio y nos permite preguntarnos por las causas de esta divergencia. Hablaré aquí de la construcción social y cultural de una ontología de la monstruosidad para el caso de estos niños y niñas. Esta ontología plantea un desafío a la hora de pensar filosóficamente la enseñanza de la filosofía, puesto que esta disciplina elabora sus reflexiones e investigaciones partiendo de un sujeto cuyas experiencias y problemas suponen una cierta “normalidad” respecto de la cual los niños y niñas trans están excluidos. Palabras clave: Identidad de género. Infancia. Ontología de la monstruosidade. Enseñanza de la filosofia. Abstract: The aim of this paper is to draw a connection between the teaching of philosophy and a specific problem concerning childhood: the fact that it appears as an inaccessible territory to many children because of their gender identity. In this sense, I attempt to present here a map of childhood as conceived by certain international agencies and local Argentine legislations that are responsible for protecting it. In so doing, I intend to contrast this map with the reality of transgender children, recovered in specific studies carried out by different political organizations. This comparison reveals the extent to which the map differs from the actual territory and allows us to raise questions about the causes of this divergence. I will refer here to the social and cultural construction of an ontology of monstrosity in the case of these children. This ontology, in turn, poses a challenge when thinking philosophically the teaching of philosophy, since this discipline reflects upon and examines the experiences and problems of a subject within the boundaries of an assumed “normality” in respect of which transgender children are excluded. Keywords: Gender identity. Childhood. Ontology of monstrosity. Philosophy teaching. REFERENCIAS 1 Autores y autoras BERKINS, Lohana; FERNÁNDEZ, Josefina (Coords.). La gesta del nombre propio: Informe sobre la situación de la comunidad travesti en la Argentina. Buenos Aires: Ediciones Madres de Plaza de Mayo, 2013. BERKINS, Lohana (Comp.). Cumbia, copeteo y lágrimas: Informe nacional sobre la situación de las travestis, transexuales y transgéneros. Buenos Aires: Ediciones Madres de Plaza de Mayo, 2015. BUTLER, Judith. Vida precaria: El poder del duelo y la violencia. Traducción de Fermín Rodríguez. Buenos Aires: Paidós, 2006. BUTLER, Judith. Marcos de guerra: Las vidas lloradas. Traducción de Bernardo Moreno Carrillo. Barcelona: Paidó, 2010. CARRERA AIZPITARTE, Luciana. Vigilar y castigar (los cuerpos): la enseñanza de la filosofía frente al sistema de opresión sexo-género. In: RODRIGUES, A., BERLE, S. y KOHAN, W., Filosofia e educação em errância: inventar escola, infâncias do pensar. Río de Janeiro: NEFI, 2018, p. 169-180. DESCOMBES, Vincent. Lo mismo y lo otro: Cuarenta y cinco años de filosofía francesa (1933-1978). Traducción de Elena Benarroch. Madrid: Cátedra, 1988. FLORES, val. Asco y heteronormatividad. Apuntes para pensar una política de las emociones en educación. II Coloquio Interdisciplinario “Educación, sexualidades y relaciones de género. Investigaciones y experiencias” – UBA, 2007. Disponible on-line: http://escritoshereticos.blogspot.com/2009/04/asco-y-heteronormatividad-apuntes-para.html. Último acceso: 29.07.2019 FLORES, val. Afectos, pedagogías, infancias y heteronormatividad. Reflexiones sobre el daño, XX Congreso Pedagógico UTE – 2015 Poéticas de las pedagogías del Sur. Educación, emancipación e igualdad, 2015. Disponible on-line: https://educacionute.org/wp-content/uploads/2016/05/Afectos-pedagogias-infancias-heteronormatividad-PONENCIA-2.pdf. Último acceso: 29.07.2019 FOUCAULT, Michel. La verdad y las formas jurídicas. Traducción de Enrique Lynch. Barcelona: Gedisa, 1996. WITTIG, Monique. El punto de vista: ¿universal o particular?. In: WITTIG, Monique. El pensamiento heterosexual y otros ensayos. Buenos Aires: Libros de la mala semilla, 2015a, p. 67-74. WITTIG, Monique. Homo Sum. In: WITTIG, Monique. El pensamiento heterosexual y otros ensayos. Buenos Aires: Libros de la mala semilla, 2015b. 2 Normativas e informes internacionales ASAMBLEA GENERAL DE LAS NACIONES UNIDAS. Declaración Universal de los Derechos Humanos, 1948. Disponible on-line: https://www.un.org/es/documents/udhr/UDHR_booklet_SP_web.pdf. Último acceso: 29.07.2019. ASAMBLEA GENERAL DE LAS NACIONES UNIDAS. Declaración de los Derechos del Niño, 1959, Disponible on-line: https://www.humanium.org/es/declaracion-de-los-derechos-del-nino-texto-completo/. Último acceso: 29.07.2019. ASAMBLEA GENERAL DE LAS NACIONES UNIDAS. Convención sobre los Derechos del Niño, 1989. Disponible on-line: https://www.ohchr.org/sp/professionalinterest/pages/crc.aspx. Último acceso: 29.07.2019. CONSEJO DE DERECHOS HUMANOS DE LAS NACIONES UNIDAS. Principios de Yogyakarta, 2007. Disponible on-line: https://www.refworld.org/cgi-bin/texis/vtx/rwmain/opendocpdf.pdf?reldoc=y&docid=48244e9f2. Último acceso: 29.07.2019. CONSEJO DE DERECHOS HUMANOS DE LAS NACIONES UNIDAS. Informe del Alto Comisionado de las Naciones Unidas por los Derechos Humanos (ACNUDH): Leyes y prácticas discriminatorias y actos de violencia cometidos contra personas por su orientación sexual o su identidad de género, 2011. Disponible on-line: https://www2.ohchr.org/english/bodies/hrcouncil/docs/19session/A.HRC.19.41_Spanish.pdf. Último acceso: 29.07.2019. FONDO DE LA NACIONES UNIDAS PARA LA INFANCIA (UNICEF). Infancia y Adolescencia. Guía para periodistas. Perspectiva de género, 2017. Disponible on-line: https://www.unicef.org/argentina/sites/unicef.org.argentina/files/2018-04/COM-1_PerspectivaGenero_WEB.pdf. Último acceso: 29.07.2019. 3 Legislación argentina ARGENTINA. Ley 23.592. Contra Actos Discriminatorios, 1988. Disponible on-line: http://www.ilo.org/dyn/natlex/docs/ELECTRONIC/6916/109135/F1790413888/ARG6916.pdf. Último acceso: 29.07.2019. ARGENTINA. Ley 26.061. Protección Integral de Niñas, Niños y Adolescentes, 2005. Disponible on-line: https://www.oas.org/dil/esp/Ley_de_Proteccion_Integral_de_los_Derechos_de_las_Ninas_Ninos_y_Adolescentes_Argentina.pdf. Último acceso: 29.07.2019. ARGENTINA. Ley 26.150. Programa Nacional de Educación Sexual Integral, 2006. Disponible on-line: http://servicios.infoleg.gob.ar/infolegInternet/anexos/120000-124999/121222/norma.htm. Último acceso: 29.07.2019. ARGENTINA. Ley 26.743. De Identidad de Género, 2012. Disponible on-line: http://servicios.infoleg.gob.ar/infolegInternet/anexos/195000-199999/197860/norma.htm. Último acceso: 29.07.2019. ARGENTINA. Ley 26.791. Modificación del Código Penal (tipificación de los crímenes por orientación sexual o identidad de género como crímenes de odio), 2012. Disponible on-line: http://servicios.infoleg.gob.ar/infolegInternet/anexos/205000-209999/206018/norma.htm. Último acceso: 29.07.2019. 4 Documentales HISTORIAS DEBIDAS: Lohana Berkins. Producido el Canal Encuentro, Televisión Pública, Argentina 2009. Disponible on-line: http://encuentro.gob.ar/programas/serie/8062/1628. Último acceso: 29.07.2019. NIÑOS ROSADOS Y NIÑAS AZULES. Estimados Producciones, Chile, 2016. Disponible on-line: https://www.youtube.com/watch?v=WfBuMoSJsTo. Último acceso: 29.07.2019.

Abstract Abstract 2661 Background: Patients with sickle cell disease (SCD) develop accumulating organ damage throughout their lives as result of chronic hemolytic anemia and ongoing microvascular vaso-occlusion. Chronic organ damage has been related to significant morbidity and increased mortality. Previous studies have shown significant increased foetal and maternal complications in patients with SCD. It is unclear whether the presence of chronic organ damage is related to pregnancy complications in these patients. Therefore, we determined the relation between chronic organ damage and pregnancy complications in women with SCD. Methods: We performed a retrospective analysis of pregnancy complications in all women known with SCD (defined as HbSS, HbS-β°, HbSC and HbSβ+) in a teaching hospital in the Netherlands. Pregnancy complications consisted of: hypertension, (pre)eclampsia, still birth, preterm birth, dysmaturity, urinary tract infection, perinatal mortality, maternal mortality, painful crisis and acute chest syndrome (ACS). In all patients vaso-occlusion related organ damage (pain rate >1 crises/year, ACS, avascular osteonecrosis and retinopathy) as well as hemolysis related organ damage (microalbuminuria, renal failure, pulmonary hypertension, chronic leg ulcers, stroke and cholelithiasis) was assessed. The patients were divided in a severe (HbSS/HbSβ°) and a mild genotype group (HbSC/HbSβ+). Chronic organ damage and the history of previous sickle cell-related complications were related to pregnancy complications, birth weight and laboratory tests. We adjusted for multiple pregnancies with the generalized estimated equations (GEE) model. Results: All 97 female patients known with SCD in our hospital were systematically evaluated for organ damage and sickle cell related complications. Thirty-six patients had not been pregnant at time of evaluation, medical information about their pregnancy was missing for 7 women and 6 women were only known with an elective abortion. Fifty-five pregnancies in 48 women with SCD (18 HbSS, 4 HbSβ0, 21 HbSC and 5 HbSβ+) were evaluated for pregnancy complications. Hemolysis related organ damage was present in 17/22 (77%) of the patients with a severe genotype and 7/32 (22%) patients with a mild genotype (p<0.001). Patients with vaso-occlusion related organ damage had more pregnancy related complications 26/32 (81%) compared to patients without vaso-occlusive related organ damage 10/19, (53%) (p=0.033). No relation between hemolysis related organ damage and pregnancy complications was found. In the severe genotype group more pregnancy complications were observed and children of patients with the severe genotype had a lower birth weight (2603±721) as compared to the milder group (2866±811) but these differences did not reach significance. Lower birth weight correlated with lower hemoglobin concentration (Hb) (r=0,326; p=0.08), leukocyte count (r=−0.438; p=0.005) and platelet counts (r=-0.368; p<0.001). With respect to laboratory test, patients with pregnancy complications had lower hemoglobin levels (p=0.031), higher leukocyte counts (p=0.006) and a lower LDH (p=0.049) in comparison to patients without any pregnancy complication. Conclusions: The majority of patients with SCD had at least one pregnancy complication. Pregnancy related complications were more frequently observed in patients with organ complications related to vaso-occlusion than patients with mainly hemolysis related complications. Furthermore, pregnancy related complications were more frequently observed in the severe genotype group with a trend to a lower birth weight and appeared to be related with lower Hb concentration, higher leukocyte and higher platelet counts. Disclosures: No relevant conflicts of interest to declare.

Background:Upadacitinib (UPA) was efficacious and well tolerated vs placebo (PBO) during the first 14 weeks (wks) of the phase 2/3 SELECT-AXIS 1 study in patients (pts) with active ankylosing spondylitis (AS) who had an inadequate response to NSAIDs.1Objectives:To report efficacy and safety of UPA through 1 year in the SELECT-AXIS 1 study.Methods:In SELECT-AXIS 1 (NCT03178487) pts were randomized 1:1 to UPA 15 mg once daily (QD) or PBO; at wk 14, pts continued in the 90-wk open-label extension and received UPA 15 mg QD; reported here are data up to wk 64. The study enrolled pts (≥18 y) with active AS (defined as BASDAI ≥4 and pt assessment of back pain ≥4 [numeric rating scale, 0–10] at screening and baseline [BL]) who had inadequate response to ≥2 NSAIDs or intolerance to or contraindication for NSAIDs and were biologic DMARD naive. Efficacy assessments included percentage of pts with Assessment of SpondyloArthritis international Society (ASAS) 20/40 response, ASAS partial remission, BASDAI50, AS Disease Activity Score (ASDAS) and change from BL in ASDAS and BASFI. Data are reported as observed and by using non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) were reported as events per 100 patient-years (PY) up to January 31, 2020.Results:Of 187 pts, 178 pts (each n=89 for UPA and PBO arms) completed wk 14 on study drug and entered the open-label extension; 160 pts completed wk 64. Efficacy was maintained or continued to improve throughout the study in the continuous UPA group: 85% (95% CI, 77%–93%) of pts achieved ASAS40 at wk 64 in the as-observed analysis and 72% (63%–81%) in the NRI analysis (Figure). Pts who switched from PBO to UPA at wk 14 showed similar speed of onset and magnitude of response vs pts initially randomized to UPA: 81% (95% CI, 72%–89%) in the as-observed analysis and 70% (61%–80%) in the NRI analysis achieved ASAS40 at wk 64 (Figure). Similar results were observed for other efficacy endpoints (Figure). Among all 182 pts receiving UPA, 618 AEs were reported. AEs leading to discontinuation and serious AEs were low (Table). No serious infections, active tuberculosis, venous thromboembolic events, gastrointestinal perforation, major adverse cardiovascular events, renal dysfunction, or deaths were reported.Table 1.TEAEs per 100 PYsEvents/(E/100 PY)UPA 15 mg QDN=182 (237.6 PY)Any AE618 (260.1)Serious AE14 (5.9)AE leading to discontinuation15 (6.3)Infections205 (86.3) Opportunistic infection*2 (0.8) Herpes zoster†5 (2.1)Creatine phosphokinase elevation‡28 (11.8)Hepatic disorder§24 (10.1)Neutropenia||7 (2.9)Anemia||3 (1.3)Lymphopenia||2 (0.8)Malignancy¶1 (0.4)Death0AE, adverse event; PY, patient-year; QD, once daily; TEAE, treatment-emergent AE; UPA, upadacitinib.*Two non-serious events of esophageal candidiasis in the same patient.†Five events in 4 patients; all non-serious and limited to 1 dermatome.‡All events were non-serious and none led to study drug discontinuation; majority were asymptomatic.§Majority based on asymptomatic alanine aminotransferase/aspartate aminotransferase elevations; all were non-serious and none led to study drug discontinuation.||All events were non-serious and none led to study drug discontinuation.¶Squamous cell carcinoma of tongue in 61-year-old male former smoker; no reasonable possibility to be study drug related per investigator.Conclusion:UPA 15 mg QD showed sustained and consistent efficacy over 1 year. Pts who switched from placebo to UPA at wk 14 showed a similar efficacy response compared with pts who received continuous UPA. No new safety findings were observed compared with safety data from the UPA clinical development program in other indications.2References:[1]van der Heijde D, et al. Lancet. 2019;394(10214):2108-2117.[2]Cohen, et al. Arthritis Rheumatol. 2019;71(suppl 10).Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by M Hovenden and J Matsuura of ICON plc (North Wales, PA) and was funded by AbbVie.Disclosure of Interests:Atul Deodhar Speakers bureau: Novartis, Pfizer, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Lilly, Novartis, Pfizer, and UCB Pharma, Joachim Sieper Speakers bureau: AbbVie, Janssen, Lilly, Merck, and Novartis, Consultant of: AbbVie, Janssen, Lilly, Merck, and Novartis, Filip van den Bosch Speakers bureau: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Novartis and Pfizer, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Andrew Ostor Consultant of: AbbVie, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, UCB, Gilead, and Paradigm, Bernard Combe Speakers bureau: AbbVie, Lilly, Merck, Consultant of: AbbVie, Lilly, Gilead, Janssen, Novartis, Roche-Chugai, and Sanofi, Grant/research support from: AbbVie and Lilly, Yunxia Sui Shareholder of: AbbVie, Employee of: AbbVie, xin wang Shareholder of: AbbVie, Employee of: AbbVie, Alvina Chu Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie

Abstract Introduction: A restrictive approach to blood transfusion was shown to be safe and effective over a decade ago, but liberal transfusion practices prevail in many institutions. In 2012, the American Association of Blood Banks published its guidelines encouraging a restrictive approach to transfusions (Carson, B J. et al. Ann Intern Med. 2012;157(1):49-58). In 2013, the American Society of Hematology, along with the American Board of Internal Medicine began a "Choosing Wisely" campaign to educate physicians to limit unnecessary blood transfusions (L K Hicks, et al. Blood. 2013 Dec 5;122(24):3879-83). These guidelines were based on over a decade of published research demonstrating the non-inferiority (and occasionally superiority) of the restrictive approach. Hemodynamically stable patients do not benefit from transfusions to a Hb >9 g/dl. (Bush, R et al. Am J Surg. 1997; 174: 143-148; Hebert, P et al. N Engl J Med 1999; 340:409-417; Barkun A N et al. Ann Intern Med. 2010; 152: 101-113; Carson, J L N Engl J Med 2011; Carson JL et al. Am Heart J. 2013; 165: 365: 2453-2462; Holst, L et al. N Engl J Med 2014;371:1381-91;). Our hospital started an active patient blood management (PBM) program in January 2013 with intensive educational lectures for all departments, addressing physician trainees as well as senior physicians. This led to a modest drop in blood utilization, but many patients continued to receive liberal transfusions. In July 2013, our institution hired a transfusion safety officer (TSO) to review all orders for blood transfusion that fell outside of the medical board approved guidelines (a restrictive policy). This report details the results of our activities and highlights the importance of one-on-one education to change practices that are ingrained over time. Methods: In January 2013, educational lectures along with pocket cards containing restrictive indications were given to the Internal Medicine, ICU, Surgical, and Ob/Gyn house staff to promote a restrictive transfusion approach. In July 2013, a TSO was hired to supplement educational efforts regarding PBM. The TSO underwent training and then trained the blood bank staff. By January 2014, the entire technical staff was trained to screen all packed red blood cell (pRBC) requests prospectively for compliance with the medical board guidelines (transfuse for Hb <7 g/dl). Previously, all pRBC transfusions were audited in a retrospective fashion. In both cases, the results of the audits were forwarded to the transfusion committee and department chairperson. If the Hb <7 g/dl: 2 units issued If the Hb 7-9 g/dl: 1 unit issued, repeat CBC requested If the Hb >9 g/dl with hemodynamic stability: question the justification If the patient was actively bleeding or hemodynamically unstable, release pRBC as requested If the MD insisted on pRBC outside guidelines, issue the units and refer to Medical Director for retrospective audit of medical necessity If no medical necessity found, refer to transfusion committee for review If final review did not meet guidelines, letter sent to MD and to department chairperson. Data including the number of pRBC transfusions, the number of patients transfused, the adjusted discharges and financials were reviewed from 2012 to 2014. Results: Table. 2012 2013 2014 pRBC (units 10,449 10,185 7,980 Patients transfused (#) 2698 2606 2167 Adjusted discharges 40,555 40,225 39,705 RBC units/adjusted discharge 0.258 0.253 0.20 Blood product expense ($) 2,901,069 2,973,863 2,406,370 Conclusion: Traditional approaches to education with grand rounds, case presentations and lectures had only a modest effect on the practice of liberal pRBC transfusions at our institution. However, one-on-one intervention with education was successful in reducing inappropriate pRBC transfusions. The above 22% decrease in RBC utilization was greater than could be accounted for by a fall in adjusted discharges, as demonstrated by the RBC/adjusted discharge ratio. In addition, there was an overall savings of $495,000 from 2012-2014 without any change in vendor or any decrease in the price of the blood products. Experience in many different medical fields has shown that influencing established medical practices is challenging. This PBM process demonstrates how patient safety and quality improvements can also lead to financial savings. Disclosures No relevant conflicts of interest to declare.

Study of petrological and geochemical characteristics of mantle peridotite xenoliths in Pliocene alkaline basalt in Nghia Dan (West Nghe An) was carried out. Rock-forming clinopyroxenes, the major trace element containers, were separated from the xenoliths to analyze for major, trace element and Sr-Nd isotopic compositions. The data were interpreted for source geochemical characteristics and geodynamic processes of the lithospheric mantle beneath the region. The peridotite xenoliths being mostly spinel-lherzolites in composition, are residual entities having been produced following partial melting events of ultramafic rocks in the asthenosphere. They are depleted in trace element abundance and Sr-Nd isotopic composition. Some are even more depleted as compared to mid-ocean ridge mantle xenoliths. Modelled calculation based on trace element abundances and their corresponding solid/liquid distribution coefficients showed that the Nghia Dan mantle xenoliths may be produced of melting degrees from 8 to 12%. Applying various methods for two-pyroxene temperature- pressure estimates, the Nghia Dan mantle xenoliths show ranges of crystallization temperature and pressure, respectively, of 1010-1044°C and 13-14.2 kbar, roughly about 43km. A geotherm constructed for the mantle xenoliths showed a higher geothermal gradient as compared to that of in the western Highlands (Vietnam) and a conductive model, implying a thermal perturbation under the region. The calculated Sm-Nd model ages for the clinopyroxenes yielded 127 and 122 Ma. 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Abstract Background: Some pilot studies already tried to investigate potential associations of leptin (LEP) and LEP receptor (LEPR) variants with coronary artery disease (CAD). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between LEP/LEPR variants and CAD in a larger pooled population. Methods: Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible case–control studies on associations between LEP/LEPR variants and CAD. The initial search was conducted in September 2018 and the latest update was performed in December 2018. Q test and I2 statistic were employed to assess between-study heterogeneities. If probability value(P-value) of Q test was less than 0.1 or I2 was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses. Results: A total of ten studies published between 2006 and 2018 were eligible for analyses (1989 cases and 2601 controls). Pooled analyses suggested that LEP rs7799039 variant was significantly associated with CAD under over-dominant model (P=0.0007, odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14–1.63, I2 = 41%, FEM) in overall population, and this significant finding was further confirmed in East Asians in subsequent subgroup analyses. However, no positive findings were observed for LEPR rs1137100 and rs1137101 variants in overall and subgroup analyses. Conclusions: Our meta-analysis suggested that LEP rs7799039 variant might affect individual susceptibility to CAD.

Abstract Background Despite being associated with health outcomes like abdominal adiposity, depression, anxiety, and cardiovascular disease risk among youth, largely, clinicians still do not adopt physical fitness testing. A clarion call for increased surveillance was previously issued, in order to address the US population-level lack of knowledge regarding pervasive inactivity among children. Because schools often do not send home annual physical fitness testing results, many lay parents are unaware of their child’s physical fitness or the risk of associated adverse health outcomes. This study investigated associations between musculoskeletal fitness measures (including 90o push-up), cardiorespiratory fitness, and weight status. Methods Two hundred and ten students (9.7 ± 1.08 years, 138.6 ± 9.4 cm; 42.3 ± 14.4 kg) across third through fifth grades were tested for cardiorespiratory (i.e., Progressive Aerobic Cardiovascular Endurance Run (PACER)) and musculoskeletal (90o push-up, trunk lift, sit-and-reach and curl-up) fitness. The relationships between measures of musculoskeletal and cardiorespiratory fitness were modeled using a series of linear regression analyses. Models were adjusted for age, sex, and weight status. Significant two-tailed tests were set at p < .05. Results Of the four musculoskeletal fitness measures, only 90o push-up was significantly associated (β = .353; p < .001) with PACER test scores (i.e., cardiorespiratory fitness). The related model (R2 = .324; F (4,205) = 26.061; p < .001) accounted for 32% of the variance in cardiorespiratory fitness. 90o push-up was associated with sit-and reach (β = .298; p < .001) and curl up (β = .413; p < = .001) test scores. When individually modeled, 90o push-up (β = −.461; p < .001) and PACER (β = −.436; p < .001) were inversely associated with weight status. Conclusions The 90o push-up test (a measure of upper body muscle strength and endurance) was associated with cardiorespiratory fitness, anterior trunk muscle strength and endurance, and lower back and posterior thigh muscle flexibility in youth aged 8–12 years old. Although the current findings do not establish a causal relationship, it is concluded that the 90o push-up test is a tractable tool for physical fitness surveillance by clinicians, parents, and possibly youth themselves.

The investigation was conducted to contribute empirical evidence of the association between going concern and financial reporting quality of listed firms on the Vietnam stock market. Based on data from 279 companies listed on the HNX and HOSE exchanges in Vietnam for the period 2009-2015, the quantitative research. Results found that the relationship between the going concern and financial reporting quality of listed firms. Research results are significant for investors, regulators to the transparency of financial reporting information. Keywords Going concern, financial reporting quality, listed firms References Agrawal, K., & Chatterjee, C. (2015). Earnings management and financial distress: Evidence from India. Global Business Review, 16(5_suppl), 140S-154S.Bergstresser, D., & Philippon, T. (2006). CEO incentives and earnings management. Journal of Financial Economics, 80(3), 511–529.Burgstahler, D., & Dichev, I. (1997). Earnings management to avoid earnings decreases and losses. Journal of Accounting and Economics, 24(1), 99–126.Charitou, A., Lambertides, N., & Trigeorgis, L. (2007a). Earnings behaviour of financially distressed firms: The role of institutional ownership. Abacus, 43(3), 271–296.Chen, Y., Chen, C., & Huang, S. (2010). An appraisal of financially distressed companies’ earnings management: Evidence from listed companies in China. Pacific Accounting Review, 22(1), 22–41Dechow, P., & Dichev, I. (2002). The Quality of Accruals and Earnings: The Role of Accrual Estimation Errors. The Accounting Review, 77, 35-59.DeFond, M., & Jiambalvo, J. (1994). Debt covenant violation and manipulation of accruals. Journal of Accounting and Economics, 17(1), 145–176.DeFond, M.L., & Park, C.W. (1997). Smoothing income in anticipation of future earnings. Journal of Accounting and Economics, 23(2), 115–139.Dichev, I., & Skinner, D. (2004). Large sample evidence on the debt covenant hypothesis. Journal of Accounting Research, 40(4), 1091–1123.Đinh Thị Thu T., Nguyễn Vĩnh K. (2016). Tác động của hành vi điều chỉnh thu nhập đến khả năng hoạt động liên tục trong kế toán: Nghiên cứu thực nghiệm cho các doanh nghiệp niêm yết tại Việt Nam, Tạp chí phát triển khoa học và công nghệ, Quí 3, tr.96-108.Đỗ Thị Vân Trang (2015). Các mô hình đánh giá chất lượng báo cáo tài chính, Tạp chí chứng khoán Việt Nam, 200, tr 18-21.Habib, A., Uddin Bhuiyan, B., & Islam, A. (2013). Financial distress, earnings management and market pricing of accruals during the global financial crisis. Managerial Finance, 39(2), 155-180.Jaggi, B., & Lee, P. (2002). Earnings management response to debt covenant violations and debt restructuring. Journal of Accounting, Auditing & Finance, 17(4), 295–324.Kasznik, R., (1999). On the association between voluntary disclosure and earnings management. Journal of accounting research, 37(1), pp.57-81.Lu, J. (1999). An empirical study of earnings management by loss-making listed Chinese companies. KuaijiYanjiu (Accounting Research), (9), 25–35.McNichols, M.F. and Stubben, S.R., (2008). Does earnings management affect firms’ investment decisions?. The accounting review, 83(6), pp.1571-1603.Selahudin, N.F., Zakaria, N.B., & Sanusi, Z.M. (2014). Remodelling the earnings management with the appear- ance of leverage, financial distress and free cash flow: Malaysia and Thailand evidences. Journal of Applied Sciences, 14(21), 2644–2661.Skinner, D.J., & Sloan, R. (2002). Earnings surprises, growth expectations, and stock returns or don’t let an earnings torpedo sink your portfolio. Review of Accounting Studies, 7(2/3), 289–312.Sweeney, A.P., (1994). Debt-covenant violations and managers' accounting responses. Journal of Accounting & Economics, 17(3): 281-308.Trần Thị Thùy Linh, Mai Hoàng Hạnh (2015). Chất lượng báo cáo tài chính và kỳ hạn nợ ảnh hưởng đến hiệu quả hoạt động của doanh nghiệp Việt Nam, Tạp chí phát triển kinh tế, 10, tr.27-50.Trương Thị Thùy Dương (2017). Nâng cao chất lượng báo cáo tài chính công ty đại chúng, Tạp chí tài chính, 1(3), tr.55-56.Uwuigbe, Ranti, Bernard, (2015). Assessment of the effects of firm’s characteristics on earnings management of listed firms in Nigeria, Asian Economic and Financial Review,5(2):218-228.

Abstract Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone (GH) deficiency is often included as an etiology. Brain and pituitary Magnetic Resonance Imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the imaging modality of choice in assessing patients with GH deficiency. Given the significant strides made in MRI technology that allow improved spatial and contrast resolution, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. We preformed a retrospective review of otherwise healthy patients with short stature and/or GH deficiency who underwent brain and pituitary MRI without and with contrast, to assess the benefit of contrast administration. Introduction: Short stature is a common concern that necessitates pediatric endocrinology evaluation. The etiologies of short stature are diverse. GH deficiency is often included as an etiology although it accounts for only 1-2% of short stature cases. The prevalence of GH deficiency is reported to be ~ 1:3500. The vast majority of GH deficiency cases are idiopathic in nature with only 20% due to organic causes. The organic causes of GH deficiency include congenital central nervous system (CNS) anomalies, tumors and other pathologic conditions that involve the pituitary-hypothalamic region. As a result, the radiological assessment of the hypothalamic-pituitary region is considered standard of care for evaluating patients with GH deficiency. Although brain and pituitary MRI is the imaging modality of choice in assessing patients with GH deficiency, its yield in cases of isolated GH deficiency is very low. In a study of 40 otherwise normal patients with isolated GH deficiency, 35 (87.5%) had normal brain MRIs. The abnormal findings of brain MRI in the minority of isolated GH deficiency cases included pituitary hypoplasia, pituitary stalk agenesis, lack of the normal T1-weighted pituitary hyperintensity in the posterior part of the sella turcica, and the presence of a high-intensity signal at the infundibular level representing ectopic neurohypophysis. Traditionally, these brain and pituitary MRI images are obtained with the use of contrast material (gadolinium). The main purpose of using contrast material is for the evaluation of pituitary microadenomas. Given the fact that significant strides made in MRI technology and pituitary microadenomas are not appeared to be associated with GH deficiency, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. GBCAs have been shown to deposit in different tissues including the kidneys and the brain. The risk increases with repeated doses. The clinical significance of this deposition is unclear at this time but warrants caution especially in pediatric population who have a longer expected lifespan to manifest any delayed effects. Allergic reactions and gastrointestinal symptoms in pediatric patients can occur with GBCA administration, although the incidence is low. Using contrast material also increases the total cost of the MRI study and prolongs the time needed to complete it. Moreover, in order to use contrast material, intravenous venous (IV) access is required which causes discomfort and additional stress to children and their families. Therefore, we performed a retrospective review of otherwise healthy patients with short stature and/or growth hormone deficiency who underwent brain and pituitary MRI without and with contrast, to assess whether contrast administration led to diagnoses that would have otherwise been missed and/or impacted the patient’s clinical course.Objectives: - To compare the diagnostic yield of non-contrast MRI with pre and post-contrast MRI of the brain and pituitary in evaluation of pediatric patients with short stature and/or growth hormone deficiency.- A secondary objective is to measure the size of the pituitary gland and correlates it with peak growth hormone levels (using insulin/argenine). Methodology: We included patients who underwent brain/pituitary MRI with/without contrast performed at our institution between Jan 2013-Dec 2018 who have short stature/GH deficiency. We excluded patients with known diagnosis of other pituitary hormone deficiencies prior to obtaining MRI studies, genetic and neurological disorders, known tumors/malignancies of any type, or renal failure. Two pediatric neuroradiologists independently reviewed the brain and pituitary MRI of these patients (each read 50% of the cohort) blinded to the clinical data and diagnoses. Each radiologist initially reviewed only the non-contrast portions of the studies, and subsequently, the same radiologist reviewed the entire study, including pre- and post-contrast portions in a separate session. The two sessions were 6 weeks apart to avoid recall bias. Several imaging findings including size and morphology of pituitary gland, presence of congenital anomalies or focal lesions and any associated intracranial findings systematically recorded, and subsequently analyzed. Hypotheses: 1.The incidence of finding congenital pituitary cysts is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency. 2.The incidence of discovering abnormal infundibulum is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency. 3.Small pituitary size correlate with GH deficiency. Results: -We identified 327 patients with short stature/GH deficiency from Jan 2013-Dec 2018-224 (68.5%) are males and 103 (31.5%) are females. -The mean age at the time of imaging is 10 years and the median is 11 years. -161 (49.24%) have height z-score &lt; -2.25 and 166 (50.76%) have height z-score &gt; -2.25.-82 (25.07%) have IGF1 z-score for age &lt; -2, 102 (31.19%) have z-score ≥-2 to ≤ -1, 141 (43.12%) have z-score &gt; -1 and 2 (0.62%) have no level done.-63 (19.27%) have GH peak &lt;5, 87 (26.61%) have GH peak 5-7.99, 53 (16.21%) have GH peak 8-9.99, 30 (9.17%) have GH peak &gt; 10 and 94 (28.75%) did not undergo GH provocative testing. -The kappa coefficient for pars intermedia cyst on pre vs. post contrast imaging is 0.74 and 0.55 for the infundibulum on pre vs. post contrast imaging. -The mean pituitary height for patients with IGF z-score &lt; -2 is 3.9 mm, 4 mm for z-score ≥- 2 to ≤ -1 and 4.3 mm for z-score &gt; -1-The mean pituitary height for patients with peak GH &lt; 5 is 3.8 mm, 4.2 mm for peak 5-7.99, 4.3 mm for peak 8-9.99 and 4.4 mm for peak &gt; 10. Conclusion: This question has not been answered or even raised in the literature. Our findings suggest that the there is no added benefit to use gadolinium when obtaining brain/pituitary MRI for the evaluation of GH deficiency/short stature. Furthermore, it seems that there is an association between the pituitary height and the GH status of the cohort which is in line with previous published studies.