A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning

Limitaciones de la Ley n.° 29904 en saneamiento físico legal de predios que comprenden proyectos de instalación de nodos de banda ancha

El trabajo de investigación tuvo como objetivo general analizar la Ley n.° 29904 que limita el saneamiento físico legal de predios destinados en la instalación de nodos de banda. En ese sentido, se aplicó un enfoque cualitativo de tipo básico con un diseño fenomenológico, asimismo, se utilizó como técnica de investigación la entrevista, con el instrumento guía de entrevista, donde los participantes fueron 5 abogados, con más de 6 años de experiencia y con especialidad en Telecomunicaciones, Saneamiento Físico Legal, Derecho Administrativo y Gestión Pública. Por consiguiente, se llegó a la conclusión que se debe establecer en la Ley n.° 29904, los lineamientos necesarios para facilitar el saneamiento físico legal de estos predios, marcos de comunicación, de acuerdo a las dimensiones, características, porcentajes de estos terrenos donde se instalará las redes de conectividad, entonces, el poder tener un marco regulatorio adecuado permitiría que se viabilice la construcción de nodos, llenado así esos vacíos legales preexistente en dicha Ley, en beneficio de los usuarios para que puedan acceder a la información con mayor velocidad y permanencia

Boletín NUESTRA AMÉRICA XXI - Desafíos y alternativas, num.7, mayo 2017

Una excelente iniciativa del Grupo de Trabajo Crisis y economía mundial, coordinado por María Josefina Morales y Gabriela Roffinelli

A low-mass triple system with a wide L/T transition brown dwarf component: NLTT 51469AB/SDSS 2131-0119

We demonstrate that the previously identified L/T transition brown dwarf SDSS J213154.43-011939.3 (SDSS 2131-0119) is a widely separated (82 ''.3, similar to 3830 au) common proper motion companion to the low-mass star NLTT 51469, which we reveal to be a close binary itself, separated by 0 ''.64 +/- 0 ''.01 (similar to 30 au). We find the proper motion of SDSS 2131-0119 of mu(alpha) cos delta = -100 +/- 20 mas yr(-1) and mu(delta) = -230 +/- 20 mas yr(-1) consistent with the proper motion of the primary provided by Gaia DR2: mu(alpha) cos delta = -95.49 +/- 0.96 mas yr(-1) and mu(delta) = -239.38 +/- 0.96 mas yr(-1). Based on optical and near-infrared spectroscopy, we classify the primary NLTT 51469A as an M3 +/- 1 dwarf, estimate photometrically the spectral type of its close companion NLTT 51469B at similar to M6, and confirm the spectral type of the brown dwarf to be L9 +/- 1. Using radial velocity, proper motion, and parallax, we derived the UVW Galactic space velocities of NLTT 51469A, showing that the system does not belong to any known young stellar moving group. The high V, W velocities, lack of a 670.8 nm Li I absorption line, and absence of H alpha emission, detected X-rays, or UV excess, indicate that the system is likely a member of the thin disc population and is older than 1 Gyr. For the parallactic distance of 46.6 +/- 1.6 pc from Gaia DR2, we determined luminosities of -1.50(-0.04)(+0.02) and -4.4 +/- 0.1 dex of the M3 and L9, respectively. Considering the spectrophotometric estimation, which yields a slightly lower distance of 34(-13)(+10) pc, the obtained luminosities are -1.78(-0.04)(+0.02) and -4.7(-0.5)(+0.3) dex. We also estimated their effective temperatures and masses, and obtained 3410(-210)(+140) K and 0.42 +/- 0.02 M-circle dot for the primary, and 1400-1650K and 0.05-0.07 M-circle dot for the wide companion. For the similar to M6 component, we estimated T-eff = 2850 +/- 200 K and m = 0.10(-0.01)(+0.06) M-circle dot.BG acknowledges support from the CONICYT through FONDECYT Postdoctoral Fellowship grant no. 3170513. This work is partly financed by the Spanish Ministry of Economy and Competitiveness through the project AYA2016-79425-C3-2-P. NL and VJSB acknowledge support from the SpanishMinistry of Economy and Competitivity through the project AYA2015-69350-C3-2-P. AP acknowledges support from the Spanish Ministry of Economy and Competitivity through the project AYA2015-69350-C3-3-P. Based on observations obtained as part of the VHS, ESO programme, 179.A-2010 (PI: McMahon). Based on observations collected at the European Organisation for Astronomical Research in the Southern hemisphere under ESO programme 092.C-0874(B). Based on observations made with the NOT, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This paper includes data obtained using the 6.5 m Magellan Clay Telescope at Las Campanas Observatory, Chile. This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. This publication makes use of data products from the Wide-field Infrared Survey Explorer, which is a joint project of the University of California, Los Angeles, and the Jet Propulsion Laboratory/California Institute of Technology, funded by the National Aeronautics and Space Administration. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. This research has made use of NASA's Astrophysics Data System. We have made use of the ROSAT Data Archive of the Max-Planck-Institut fur extraterrestrische Physik (MPE) at Garching, Germany. This research has made use of theWashington Double Star Catalog maintained at the U.S. Naval Observatory

Memoria del XVIII Seminario de Economía Mexicana. La economía en el Segundo año del gobierno de Fox

Fundado por el maestro José Luis Ceceña Gámez en 1983, el Seminario de Economía Mexicana se ha convertido en un importante espacio de reflexión económica para los investigadores de la UNAM y de otras instituciones, a través de diecisiete reuniones anuales orientadas a examinar temas relevantes de —y para— la economía mexicana. En su dieciochoava edición, que ahora iniciamos, el Seminario tendrá como tema general: La economía mexicana durante el segundo año del gobierno de Fox. Evaluación y alternativas. Será un ejercicio académico orientado a examinar el estado en que se encuentra la economía mexicana, las condiciones del entorno económico internacional, las políticas económicas desplegadas por el gobierno del presidente Fox, y las propuestas viables de política económica alternativa capaces de superar el pobre y errático desempeño mostrado por la economía mexicana durante las dos últimas décadas

Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1 Mutant Myelodysplastic Syndromes With Ringed Sideroblasts

View full abstracthttps://openworks.mdanderson.org/leading-edge/1025/thumbnail.jp

SF3B1-mutant MDS as a distinct disease subtype:a proposal from the International Working Group for the Prognosis of MDS

The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDSas a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overtMDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement. (Blood. 2020;136(2):157-170)

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features

TOI-2285b: A 1.7 Earth-radius planet near the habitable zone around a nearby M dwarf

We report the discovery of TO1-2285b, a sub-Neptune-sized planet transiting a nearby (42 pc) M dwarf with a period of 27.3 d. We identified the transit signal from the Transiting Exoplanet Survey Satellite photometric data, which we confirmed with ground-based photometric observations using the multiband imagers MuSCAT2 and MuSCAT3. Combining these data with other follow-up observations including high-resolution spectroscopy with the Tillinghast Reflector Echelle Spectrograph, high-resolution imaging with the SPeckle Polarimeter, and radial velocity (RV) measurements with the InfraRed Doppler instrument, we find that the planet has a radius of 1.74 +/- 0.08 R-circle plus, a mass of &lt;19.5 M-circle plus + (95% c.I.), and an insolation flux of 1.54 +/- 0.14 times that of the Earth. Although the planet resides just outside the habitable zone for a rocky planet, if the planet harbors an H2O layer under a hydrogen-rich atmosphere, then liquid water could exist on the surface of the H2O layer depending on the planetary mass and water mass fraction. The bright host star in the near-infrared (K-s = 9.0) makes this planet an excellent target for further RV and atmospheric observations to improve our understanding of the composition, formation, and habitability of sub-Neptune-sized planets