Investment and Abandonment Decisions in the Presence of Imperfect Aggregation of Information

The traditional marshallian rule of investing when the value of the investment is greater than its installment cost is modified in the presence of irreversibility and uncertainty, giving rise to an option component. Additionally, the interaction of participants holding each one a right to invest can give rise under imperfect information to situations of deviations from the optimal timing of exercise of the investment and to herd behavior or informational cascades given that the agents take into account when deciding not only their private set of information but also the information released to the market by the decisions made by the other agents. In the present paper we develop a model that tries to capture these effects and dynamics by showing revision of conditional expectations of the agents, and with considerations regarding the degree of dispersion of information in the economy and the effect of the number of participants and their effect into their behavior

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Geoarchaeology and paleontology of the Late Pleistocene deposits at the former Abroñigal Stream (Manzanares Basin, Madrid): the Puente de Los Tres Ojos

RESUMEN: La excavación arqueológica del yacimiento del Puente de los Tres Ojos, próximo a la calle Cerro Negro (Madrid), ha aportado nuevos datos para profundizar en el conocimiento de la ocupación humana y en la reconstrucción paleoambiental del valle del antiguo arroyo Abroñigal, cuyo curso fluvial funcionó como afluente del río Manzanares posiblemente desde antes del Pleistoceno Superior hasta la segunda mitad del siglo XX. En el presente artículo se incluyen los aspectos geomorfológicos y cronoestratigráficos de los niveles excavados, documentándose varias secuencias fluviales y aluviales de relleno de la margen derecha del fondo de valle del Abroñigal en su tramo inferior. Durante la excavación se registró un amplio conjunto lítico, formado en su mayoría por piezas recuperadas en niveles de arenas y gravas correspondientes a episodios fluviales de media energía, a las que hay que añadir un porcentaje menor localizado en niveles de limos arcillosos y arenas finas. La mayor parte del conjunto lítico responde a sistemas técnicos propios del Paleolítico Medio, aunque destaca la presencia testimonial de piezas del Paleolítico Superior, además derestos de fauna de mamíferos correspondientes al Pleistoceno Superior, todo ello en niveles datados por OSL entre 14.400 y 11.170 años BP aproximadamente.ABSTRACT: The archaeological excavation of the Puente de los Tres Ojos site, next to Cerro Negro Street (Madrid), has provided new data that has allowed us to go in depth into the human settlement and the palaeoenvironmental reconstruction of the old Abroñigal stream valley, whose fluvial course worked as a tributary of the Manzanares River probably from before the Late Pleistocene up to the second half of the XXth century. In this paper we present the geomorphological and chronostratigraphic data of the excavated layers, documenting the various sequences of the fluvial and alluvial deposits that have filled the right bank of the Abroñigal valley bottom within its lower stretch. A large collection of lithic pieces has been obtained during the excavation works, most of which have been found within medium energy deposits of sands and gravels, being the rest associated to argillaceous slimes and thin sand deposits. The majority of the lithic collection responds to technical systems of the Middle Palaeolithic, although it is noteworthy the testimonial presence of pieces belonging to the Upper Palaeolithic, as well as mammal faunal remains from the Late Pleistocene. The dates obtained through OSL place the chronology of the deposit between approximately 14,400 and 11,170 years BP.Peer reviewe

Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP)

Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non‐haematological toxicity. The 12‐month overall survival and event‐free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab

The relapsed acute lymphoblastic leukemia network (ReALLNet) : a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP)

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL

Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER).Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of NOTCH1, FBXW7, PTEN, and RAS mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients