La iniciativa de la transparencia en la industria extractiva y los derechos humanos en el sector de los hidrocarburos

Les relacions internacionals han patit canvis significatius en les darreres dècades, en bona part a causa de la proliferació d'actors no estatals, com ara les empreses multinacionals, que actuen en un ordenament jurídic internacional encara definit per als estats. En aquest context, el problema de la seva regulació en l'àmbit internacional encara continua vigent, especialment en relació amb el dret internacional dels drets humans. Així, per fer front als desafiaments que plantegen les empreses, la responsabilitat social empresarial s'ha determinat com una solució alternativa i complementària a l'àmbit purament jurídic. Per això, aquesta recerca ha centrat l'anàlisi en les empreses del sector dels hidrocarburs, i ha examinat si les principals eines sectorials de responsabilitat social empresarial estan fent front als riscos més significatius per als drets humans derivats de la seva activitat. En particular, s'ha examinat de manera exhaustiva l'EITI, que té com a missió fomentar la transparència i millorar la rendició de comptes, a través de dos països membres de la iniciativa (Nigèria i Colòmbia).Las relaciones internacionales han sufrido cambios significativos en las últimas décadas, en buena medida debido a la proliferación de actores no estatales, como las empresas multinacionales, que actúan en un ordenamiento jurídico internacional todavía definido para los estados. En este contexto, el problema de su regulación en el ámbito internacional todavía sigue vigente, en especial en relación con el derecho internacional de los derechos humanos. Así, para hacer frente a los desafíos que plantean las empresas, se ha determinado la responsabilidad social empresarial como una solución alternativa y complementaria al ámbito puramente jurídico. Para ello, esta investigación ha centrado su análisis en las empresas del sector de los hidrocarburos, y ha examinado si las principales herramientas sectoriales de responsabilidad social empresarial están haciendo frente a los riesgos más significativos para los derechos humanos derivados de su actividad. En particular, se ha examinado de forma exhaustiva el EITI, cuya misión es fomentar la transparencia y mejorar la rendición de cuentas, a través de dos países miembros de la iniciativa (Nigeria y Colombia).International relations have undergone significant changes in recent decades, largely due to the proliferation of non-state actors, such as multinational enterprises, which act in an international legal order still defined for states. In this context, the problem of their regulation in the international context remains under debate, especially in relation to international human rights law. To address the challenges posed by companies, corporate social responsibility (CSR) has been identified as a solution that can work as an alternative to the law but also complement it. To explore this, this research has focused its analysis on companies in the hydrocarbons sector and has examined whether the main sectoral CSR tools are addressing the most significant risks to human rights derived from the companies' activity. In particular, the Extractive Industry Transparency Initiative, whose mission is to promote transparency and improve accountability, has been exhaustively examined through two of the initiative's member countries (Nigeria and Colombia).Societat de la informació i el coneixemen

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo.

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)-directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies. Engineered T cells secreting TCE antibodies (STAb) represent a promising strategy that combines the advantages of adoptive cell therapies and bispecific antibodies. Here, we undertook a comprehensive preclinical study comparing the therapeutic potential of T cells either expressing second-generation anti-BCMA CARs (CAR-T) or secreting BCMAxCD3 TCEs (STAb-T) in a T cell-limiting experimental setting mimicking the conditions found in patients with relapsed/refractory multiple myeloma. STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro. These advantages led to robust expansion and persistence of STAb-T cells in vivo, generating long-lived memory BCMA-specific responses that could control multiple myeloma progression in xenograft models, outperforming traditional CAR-T cells. These promising preclinical results encourage clinical testing of the BCMA-STAb-T cell approach in relapsed/refractory multiple myeloma.Acknowledgments: We would like to thank the cell Sorting Service of the nUcleUS platform (University of Salamanca, Salamanca, Spain) for technical assistance. Funding: Financial support for this work was obtained from the Spanish Ministry of Science and innovation Mcin/Aei/10.13039/501100011033 (PiD2020- 115444GB- i00 to P.r.- n., PiD2019- 108160rB- i00 to P.M., Ple2021- 0075 to c.B., and PiD2020- 117323rB- 100 and PDc2021- 121711- 100 to l.Á.-V.), partially supported by the european regional Development Fund (erDF); the carlos iii health institute (iSciii) (Pi20/01030 to B.B., Pi19/00132 to l.S., Pi21- 01834 to P.P., Pi20/00822 to c.B., and DTS20/00089 to l.Á.-V.), partially supported by the erDF; the iSciii- ricorS within the next Generation eU program (plan de recuperación, Transformación y resilencia) (rD21/0017/0030 to B.B. and J.M.- l. and rD21/0017/0029 to P.M.); the iSciii- ciBeronc program (cB16/12/00400 to A.o.), the criS cancer Foundation (FcriS- 2021- 001 to J.M.- l. and FcriS- 2021- 0090 to l.Á.-V.), the Spanish Association Against cancer (Aecc) (PrYGn234975Mene to P.M., PrYGn211192BUen to c.B., and ProYe19084AlVA and PrYGn234844AlVA to l.Á.-V.); the Accelerator Award- cancer research UK/Airc/Aecc- incAr (GeAcc18001orF to A.o.), the Fundación “la caixa” (lcF/Pr/hr19/52160011 to P.M. and hr21- 00761 project il7r_lungcan to l.Á.-V.), the european research council (erc) (erc- Poc- 957466 to P.M.) and erc under the eU’s horizon Program (grant agreement 101100665 to P.M.), the Fundación de investigación Biomédica 12 de octubre (programa investiga 2022- 0082) to l.Á.-V.; the Fundación ramón Areces to P.P. l.D.-A. was supported by a rio hortega fellowship from the carlos iii health institute (cM20/00004). A.F. was supported by a postdoctoral fellowship from the Spanish Ministry of Science and innovation (FJc2021- 046789- i). A. Mayado was supported by the ciBeronc (PrF- 2869). A.P.- P. was supported by a grant from the Government of castilla y león (orden eDU/556/2019; Valladolid, Spain). M.G.- r. was supported by an industrial PhD ellowship from the comunidad de Madrid (inD2022/BMD- 23732). o.A.- S. was supported by a PhD fellowship from the complutense University of Madrid. c.D.-A. was supported by a PhD fellowship from the Spanish Ministry of Science and innovation (Pre2018- 083445). l.r.- P. was supported by a PhD fellowship from the immunology chair, Universidad Francisco de Vitoria/Merck. o.h. was supported by an industrial PhD fellowship from the comunidad de Madrid (inD2020/BMD- 17668). A.V. is supported by research institute hospital 12 de octubre (imas12). A.G.- o. is supported by hiGeA 2019/0123 Aie project to J.M.- l.S