Cold H2O and CO ice and gas toward the Galactic Center

We present observations of CO, 13CO and of H2O in the middle and far-infrared taken with the ISO-SWS and ISO-LWS spectrometers toward two positions in the Galactic Center region (Sgr A* and GCS-3). Both ice and gas phase molecules are detected. The ISO data have been complemented with observations of the J=3-2 and J=7-6 lines of CO carried out at the Caltech Submillimeter Observatory. The ISO and CSO data indicate that the absorbing gas is extremely cold, T_K ~ 10 K, suggesting that it is located in the dark clouds of the different spiral arms that intersect the line of sight towards the Galactic Center. From the analysis of the CO absorption we derive 13CO gas phase column densities of 1.1 and 0.7E17 cm-2 towards Sgr A* and GCS-3, respectively. The H2O gas column density in the direction of Sgr A* is ~ 2E16 cm-2. The derived CO/H2O and gas/solid abundance ratios corresponding to these cold clouds are remarkably similar along the two lines of sight. We find that nearly all the CO is in the gas phase, while the H2O is almost entirely frozen onto the surfaces of cold dust grains. Finally, the N_{gas+ice}(CO)/N_{gas+ice}(H2O) abundance ratio is ~5 implying that H2O formation processes are highly efficient.Comment: Accepted by ApJ Letter

Bioinspired Functional Catechol Derivatives through Simple Thiol Conjugate Addition

The combination of the surface-adhesive properties of catechol rings and functional moieties conveying specific properties is very appealing to materials chemistry, but the preparation of catechol derivatives often requires elaborate synthetic routes to circumvent the intrinsic reactivity of the catechol ring. In this work, functional catechols are synthesized straightforwardly by using the bioinspired reaction of several functional thiols with o-benzoquinone. With one exception, the conjugated addition of the thiol takes place regioselectively at the 3-position of the quinone, and is rationalized by DFT calculations. Overall, this synthetic methodology provides a general and straightforward access to functional and chain-extended catechol derivatives, which are later tested with regard to their hydro-/oleophobicity, colloidal stability, fluorescence, and metal-coordinating capabilities in proof-of-concept applications

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Biomarcadores; Eventos adversos relacionados con el sistema inmunitario; InmunoterapiaBiomarcadors; Esdeveniments adversos relacionats amb el sistema immunitari; ImmunoteràpiaBiomarkers; Immune related adverse events; ImmunotherapyImmune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response. We assembled a retrospective cohort of 262 NSCLC patients treated with ICIs, compiled relevant clinicopathological characteristics, and studied their associations with treatment outcome using Cox proportional-hazards survival models. Additionally, we investigated the interrelations between clinicopathological features and devised a method to create a compendium associated with ICIs response by selecting those that provide non-redundant information. In multivariate analyses, ECOG performance status (hazard ratio (HR) 1.37 (95% CI 1.11 to 1.68), p < 0.005), LDH (HR 1.24 (95% CI 1.03 to 1.48), p = 0.02)) and PD-L1 negativity were associated with decreased progression-free survival (PFS) (HR 1.92 (95% CI 1.03 to 3.58), p = 0.04), whereas presentation of immune-related adverse events (irAEs) (HR 0.35 (95% CI 0.22 to 0.55, p < 0.005) or females (HR 0.52 (95% CI 0.33 to 0.80, p < 0.005) had longer PFS. Additionally, numerous clinicopathological indicators were found to be interrelated. Thus, we searched for features that provide non-redundant information, and found the combination of LDH levels, irAEs, and gender to have a better association with ICIs treatment response (cross-validated c-index = 0.66). We concluded that several clinicopathological features showed prognostic value in our real-world cohort. However, some are interrelated, and compendiums of features should therefore consider these interactions. Joint assessment of LDH, irAEs, and gender may be a good prognostic compendium.None associated with this project

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Corticosteroids; Efficacy; Immune checkpoint inhibitorsCorticosteroides; Eficacia; Inhibidores del punto de control inmunitarioCorticoides; Eficàcia; Inhibidors del punt de control immunitariIn recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established. Immune checkpoint inhibitors (ICIs), block these interactions, and when administered not only as monotherapy but also as part of combination regimens, have shown to improve survival results in multiple advanced cancers leading to an increasing number of patients treated with ICI and, as a consequence, a rise in the number of patients developing immune-related adverse events (irAEs). Presence of irAEs has been associated with greater benefit from treatment, especially when blocking PD-L1. Recent data suggests that treatment benefit persists after discontinuation of ICIs due to a treatment related adverse event, regardless of the grade. Patients experiencing grade 3-4 irAEs are at risk of toxicity recurrence after reintroducing immunotherapy and therefore, the decision to resume the treatment is challenging. In these cases, a multidisciplinary approach is always needed and several factors should be considered. Management of severe toxicities may require systemic corticosteroids which can impact on T-cell function. Due to their immunosuppressive properties, it is necessary to deeper determine how corticosteroids influence responses. In terms of overall survival (OS), the use of steroids as therapy for irAEs seems not to reduce OS and several studies have reported durable responses in patients experiencing autoimmune toxicities treated with corticosteroids

Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort

Cancer therapy; MesotheliomaTerapia del cáncer; MesoteliomaTeràpia del càncer; MesoteliomaCheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d’Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan–Meier method. 189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95% CI 17.2–24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in non-epithelioid patients (HR 2.25 CI 95% 1.4–3.4; p < 0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in non-epithelioid (HR 1.5 CI 95% 1.0–2.3; p = 0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS = 0.09, p of interaction OS = 0.65). In our series, patients with non-epithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy

Ensayo de una tipología de las cuencas mediterráneas del proyecto GUADALMED siguiendo las directrices de la Directiva Marco del Agua

RESUMEN Utilizando la propuesta de tipología de ríos de la Directiva Marco del Agua en su anexo 2 se realiza un ensayo tipológico de los puntos de muestreo del proyecto GUADALMED. Según el sistema A, se presentan 16 ecotipos, lo que se juzga poco adecuado para la gestión de los mismos y sin una base ecológica que lo justifique. De acuerdo con la selección previa hecha por los miembros del grupo GUADALMED para 5 de estos ecotipos no habría estaciones de referencia. Con algunas variables medidas en los puntos de muestreo y otras de tipo geológico e hidromorfológico, se realiza un ensayo tipológico usando el sistema B. El método implica un análisis de la correlación entre variables, un cluster de las estaciones utilizando el método K-means y un análisis discriminante de cuáles son las variables que distinguen estos grupos. El estudio da como resultado la caracterización de 6 ecotipos que sin embargo, a juicio de los miembros del proyecto GUADALMED, no recogen la variedad de tipos de ríos mediterráneos. Valorando cualitativamente parámetros no introducidos (por falta de datos) en el análisis K-means, se propone una tipología provisional en 9 grupos. Un análisis de las comunidades de macroinvertebrados (a nivel taxonómico de familia) revela un grado importante de coherencia entre las familias asociadas a cada tipo y sus preferencias ecológicas conocidas. ABSTRACT A preliminary analysis was conducted of the river types in the GUADALMED project using the river typology proposed in the Water Framework Directive (WFD) in its annex 2. Using System A, 16 different types were found, a number too high for water management purposes and such typology lacks a supportive ecological basis. For 5 of these 16 ecotypes, no reference stations exist. Reference stations were selected a priori in project GUADALMED for each of the 12 basins sampled. An ecotypological analysis was performed using System B of the WFD using several variables measured during the study, and other variables obtained from maps or data bases (e.g., geology). The method included the analysis of the calibration between variables, the clustering of stations by the K-means method and a discriminant analysis. The latter revealed which factors were distinctive of each group. Six ecotypes were established for the GUADALMED study sites. These, however, do not include all the mediterranean-type streams of the region. This is mainly due to the absence in the data base of some important features of streams in the data base such as temporality or the dependence of flow on the presence of karstic aquifers, attribute

Expression of TILs and Patterns of Gene Expression from Paired Samples of Malignant Pleural Mesothelioma (MPM) Patients

Gene expression; Immunotherapy; Malignant pleural mesotheliomaExpresión génica; Inmunoterapia; Mesotelioma pleural malignoExpressió gènica; Immunoteràpia; Mesotelioma pleural maligneMPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors. The aim of our study is to identify the effect of treatment on immune cells and the immune gene profile in MPM. We investigated the changes in expression of TILs in 10 human MPM paired tumor tissues using immunohistochemistry and gene expression analysis from paired untreated and treated samples. In this small series, we demonstrated that during the evolution of disease without any treatment there was an increase in the inflammatory component in tumor samples. After systemic treatment there was a decrease in the number of TILs. We observed that after systemic treatment or disease progression immune gene signatures were suppressed. Our integrated analysis of paired samples with immune profile and genomic changes on MPM suggested that during the evolution of the disease the immune system tends to switch, turning off with treatment.The study was partially funded by Project PREDICT-Meso (GEACC19003CED), funded by Fundación AECC

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases : multicentre study of 80 patients

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis