La fotografía de Nigel Henderson y la escuela en Hunstanton de A+P Smithson: una instantánea de la posguerra inglesa

Alison and Peter Smithson were great lovers of art and also were very interested in its evolution throughout history. After World War II, as certain functionalist reasonings from the architecture of the Modern Movement began to be questioned, from an artistic point of view the evolution of the dadaist material inside the surrealist movement started to be also questioned. In its multidisciplinary affiliation to the “Independent Group”, the Smithson met several artists who shared the same creative philosophy, among which was Nigel Henderson (1917-1985). Nigel Henderson can be considered a forgotten British pop culture pioneer whose work was focused on the photographic experimentation. When he moved to Bethnal Green (East London) he found a social reality more genuine and characteristic of postwar Britain and decided to turn it into his artistic theme. The two-dimensional imagery of Henderson is expanded by the Smithson’s three-dimensional space projected through its facade. The building skin has managed to continue exposing the school reality, so this establishes a new set of moving images. Each facade module is a sort of changing frame that converts the big surfaces in a video-sequence. Hunstanton School symbolises a real architectural event, a “snapshot” of its time, and reaffirms the importance the image as a document in the art world began to have. Despite the changes occurred in the building in order to adapt to the new programmatic requirements, flexibility of space and the “hologramic” capacity of its facade allow to develop a set of updated contents and images, perverting the definition of the initial temporality.Alison y Peter Smithson fueron unos grandes amantes del arte y, además, estaban muy interesados en la evolución del mismo a lo largo de la Historia. Tras la Segunda Guerra Mundial, al igual que se comenzaron a poner en duda determinados razonamientos funcionalistas característicos de la arquitectura del Movimiento Moderno, desde el punto de vista artístico se empezó a cuestionar el devenir dadaísta del material procedente del Movimiento Surrealista. En su filiación multidisciplinar al Independent Group, los Smithson conocieron a varios artistas que participaban de su misma filosofía creativa, entre los que destacaba Nigel Henderson (1917- 1985). Nigel Henderson puede considerarse un pionero olvidado de la cultura pop británica cuyo trabajo giraba en torno a la experimentación fotográfica. Cuando se mudó al barrio de Bethnal Green descubrió una realidad social que participaba de una cotidianeidad más genuina y característica de la Gran Bretaña de posguerra y decidió convertirla en material de estudio. El imaginario bidimensional de Henderson se extiende sobre el espacio tridimensional proyectado por los Smithson a través de su fachada. La piel del edificio ha conseguido seguir exponiendo la realidad docente constituyendo un nuevo conjunto de imágenes en movimiento. Cada módulo de cerramiento constituye una suerte de frame cambiante que convierte la fachada en video-secuencia. La escuela en Hunstanton simboliza un verdadero acontecimiento arquitectónico, una “instantánea” del momento en que fue engendrada y corrobora la importancia que comienza a tener la imagen como documento en el mundo del arte. A pesar de las modificaciones acaecidas en el edificio con el fin de adaptarse a los nuevos requerimientos programáticos, la flexibilidad del espacio y la capacidad “holográmica” de su envolvente permiten desenvolver un juego de actualización de contenidos e imágenes, pervirtiendo la definición de temporalidad inicial

A comprehensive hydrodynamic analysis of a full-scale oxidation ditch using Population Balance Modelling in CFD simulation

This work exhibits the importance of the experimental validation when full-scale computational fluid dynamics (CFD) models are developed to provide a detailed analysis of the spatial variations in 3D of the fluid flow inside aerated tanks. Single-phase and two-phase CFD models were performed to study the fluid behaviour carefully by means of the velocity profiles and the aeration pattern in a full-scale oxidation ditch. Air hold-up, bubble size distribution and interfacial area density were calculated by polydisperse models where Population Balance Model (PBM) was governed by break-up and coalescence; the free-surface approach allowed the CFD model to describe the three-dimensional effect of bubbly plumes in large scales in detail. Tracer tests were carried out to obtain the flow pattern and the hydraulic distribution of the flow into two wastewater treatment lanes in order to define the boundary conditions for the model correctly. Despite the difficulty of performing velocity measurements of the fluid in 3D, with and without air bubbles, these provided essential information to validate the CFD model. From this analysis, several simulations were performed to improve the hydrodynamics and the operation of the process by relocating the propellers

Early imaging and molecular changes with neoadjuvant bevacizumab in stage ii/iii breast cancer

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)-and18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre-and post-bevacizumab vascular changes were evaluated using dynamic contrastenhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p = 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Disminución de la reserva de flujo coronario en pacientes con insuficiencia cardíaca no isquémica

Introduction and objectives. Coronary flow reserve (CFR) is impaired not only in ischemic heart disease, but also in cardiac diseases that may or may not course with heart failure. The aim of the present study was to determine if the severity of heart failure can influence CFR impairment. Methods. Forty patients with non-ischemic heart disease and heart failure were studied 41 times. Four groups were established: 1. 10 patients in functional class III-IV; 2. 10 patients in functional class II not taking beta-blockers; 3. 11 patients in class II treated with carvedilol, and 4. 10 patients in class I. These patients had a history of heart failure and systolic dysfunction. Myocardial blood flow (MBF) was measured with positron emission tomography (PET) and N-13 ammonia at rest (r) and during adenosine triphosphate (ATP) infusion. Results. MBF and CFR were significantly higher in group 4 (1.95 ± 0.58 and 2.40 ± 0.95 ml/min/g) than in group 1 (1.02 ± 0.52 and 1.46 ± 0.48 ml/min/g). CFR tended to be higher in groups 2 (1.73 ± 0.72), and 3 (1.89 ± 0.75) vs group 1. No significant correlation was found between CFR and the following variables: age, systolic blood pressure, ventricular mass index, ventricular volume indexes, and ejection fraction. Conclusions. Coronary microvascular function is impaired in non-ischemic heart failure, and the impairment is related to functional class, regardless of the underlying responsible heart disease

Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome

To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high-resolution comparative genomic hybridization (CGH) to bacterial artificial chromosome (BAC) microarrays in 68 patients and 9 MCL-derived cell lines. Array CGH defined an MCL genomic signature distinct from other B-cell lymphomas, including deletions of 1p21 and 11q22.3-ATM gene with coincident 10p12-BMI1 gene amplification and 10p14 deletion, along with a previously unidentified loss within 9q21-q22. Specific genomic alterations were associated with different subgroups of disease. Notably, 11 patients with leukemic MCL showed a different genomic profile than nodal cases, including 8p21.3 deletion at tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55% versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015). Additionally, leukemic MCL exhibited frequent IGVH mutation (64% versus 21%; P = .009) with preferential VH4-39 use (36% versus 4%; P = .005) and followed a more indolent clinical course. Blastoid variants, increased number of genomic gains, and deletions of P16/INK4a and TP53 genes correlated with poorer outcomes, while 1p21 loss was associated with prolonged survival (P = .02). In multivariate analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival (hazard ratio [HR], 6; confidence interval [CI], 2.3 to 15.7). Our study highlights the genomic profile as a predictor for clinical outcome and suggests that "genome scanning" of chromosomes 1p21, 9q21-q22, 9p21.3-P16/INK4a, and 17p13.1-TP53 may be clinically useful in MCL

Expert recommendations on the management of patients with metastatic castration-resistant prostate cancer who progress after CHAARTED or LATITUDE

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ¿7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms

Evaluation of spacial resolution of a PET scanner through the simulation and experimental measurement of the Recovery coefficient

Purpose: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures. Methods: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources. Results: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure. Conclusion: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.The Spanish Ministerio de Ciencia e Innovacion, ´ Programa Retos en Investigacion ´ (grant number PID2019-104406RB-100) to MJC provided the financial support for the conduct of the research included in this manuscript. Garantia Juvenil program from Comunidad de Madrid contributed with the research assistant contract to M-R, O

Recommendations by the Spanish Society of Hospital Pharmacy, the Spanish Society of Oncology Nursing and the Spanish Society of Medical Oncology for the safe management of antineoplastic medication in cancer patients

Aim: To define recommendations that permit safe management of antineoplastic medication, minimise medication errors and improve the safety of cancer patients undergoing treatment. Methods: By reviewing the literature and consulting the websites of various health organisations and agencies, an expert committee from the Spanish Society of Hospital Pharmacy and the Spanish Society of Medical Oncology defined a set of safe practices covering all stages of providing cancer therapy to patients. The Spanish Society of Oncology Nursing revised and endorsed the final list. Results: In total, 68 recommendations arranged in five sections were defined. They include issues concerning the training of health professionals, the technological resources needed, treatment planning, informing the patient and his/her family, the processes of prescribing, preparing, dispensing and administering cancer therapy (orally, parenterally or intrathecally), assessing patient adherence and treatment toxicity. Conclusions: It is essential for healthcare establishments to implement specific measures designed to prevent medication errors, in order to ensure the safety of cancer patients treated with antineoplastic medication

Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling

Although conventional therapies for acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) are effective in inducing remission, many patients relapse upon treatment. Hence, there is an urgent need for novel therapies. PIM kinases are often overexpressed in AML and DLBCL and are therefore an attractive therapeutic target. However, in vitro experiments have demonstrated that intrinsic resistance to PIM inhibition is common. It is therefore likely that only a minority of patients will benefit from single agent PIM inhibitor treatment. In this study, we performed an shRNA-based genetic screen to identify kinases whose suppression is synergistic with PIM inhibition. Here, we report that suppression of p38α (MAPK14) is synthetic lethal with the PIM kinase inhibitor AZD1208. PIM inhibition elevates reactive oxygen species (ROS) levels, which subsequently activates p38α and downstream AKT/mTOR signaling. We found that p38α inhibitors sensitize hematological tumor cell lines to AZD1208 treatment in vitro and in vivo. These results were validated in ex vivo patient-derived AML cells. Our findings provide mechanistic and translational evidence supporting the rationale to test a combination of p38α and PIM inhibitors in clinical trials for AML and DLBCL