Advances in targeted Alpha therapy for prostate cancer

BACKGROUND: Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. DESIGN: In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. RESULTS: A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor (AR)-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. CONCLUSIONS: The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment

Time Budget in Two Desert Gerbils: is the Diet Important?

We studied time budgets and dietary intake in two desert gerbillids, Psammomys obesus, a diurnal herbivore, and Meriones crassus, a nocturnal granivore feeding three different types of diet (millet seeds together with leaves of Atriplex halimus for M. crassus, fresh leaves of A. halimus or fresh stems of Anabasis syriaca for P. obesus). M. crassus spent the lowest proportion of its time budget for feeding compared to P. obesus. Number of feeding sessions in M. crassus was approximately the same but each separate feeding session was almost three times shorter than those in P. obesus. No difference in temporal pattern of feeding was found between P. obesus fed different plants, in spite of sharp differences in chemical composition of food. P. obesus fed A. halimus was active significantly less time than M. crassus, whereas P. obesus fed A. syriaca stayed active the same time as M. crassus. Dry matter intake of P. obesus fed A. halimus was much higher than that of M. crassus and dry matter intake of P. obesus fed A. syriaca was lower than even that in M. crassus

Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136004/1/em22071.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136004/2/em22071_am.pd

La recherche expérimentale en aérodynamique à l’ONERA – L’exemple du buffet transsonique

International audienceThe paper reviews research conducted at ONERA over the last thirty years on the transonic buffet. We first present the transonic buffet phenomenon and we explain its importance for aeronautical applications. Then, a distinction is made between the 2D buffet produced by an airfoil and the 3D buffet that characterizes swept wings of finite span. The 2D buffet amounts to a pure oscillation of the shock phase-locked with the detachment and reattachment of the boundary layer downstream, whereas the 3D buffet takes the form of a pocket of broadband perturbations located in a limitedportion of the wing. We recall that these mechanisms were first studied in the 1980s through a series of tests conducted in the transonic wind tunnel ONERA T2 at Toulouse and in the large transonic wind tunnel ONERA S2Ma at Modane. Since this pioneering work, progress in the measurement techniques has led to the constitution of a comprehensive database of the 2D buffet that we describe. This database, obtained in the wind tunnel ONERA S3Ch at Meudon, has been extensively used to validate various CFD tools, with the latter being used in turn to investigate the buffet physics. We illustrate this collaboration between simulation and physics by recalling that a linear stability analysis of accurate Reynolds-Averaged-Navier-Stokes (RANS) solutions made it possible to prove that the buffet on a 2D airfoil stems from a global instability mechanism.We also review more recent tests done in the case of a laminar airfoil, which reveal very distinct behaviors of the buffet flow. This illustrates how sensitive the buffet is to the nature of the boundary layer. The last section of the paper gives a short overview of advanced simulations for these different test cases. In the conclusion, we list research perspectives, which include some more general topics such as data assimilation.L'article passe en revue les recherches menées à l'ONERA au cours des trente dernières années sur le buffet transsonique. Nous présentons d'abord le phénomène du buffet transsonique et nous expliquons son importance pour les applications aéronautiques. On distingue ensuite le buffet 2D produit par une aile bidimensionnelle et le buffet 3D qui caractérise les ailes en flèches d’envergure finie. Le buffet 2D se présente sous la forme d’une oscillation d’ensemble de tout l’écoulement couplant un déplacement de l’onde de choc et le décollement de la couche limite en aval de ce choc. Le buffet 3D prend quant à lui la forme d'une poche de perturbations localisées dans une portion limitée de l'aile. Nous rappelons que ces mécanismes ont d'abord été étudiés à l’ONERA dans les années 80 à travers une série de tests réalisés dans la soufflerie transsonique T2 à Toulouse et dans la grande soufflerie transsonique S2 de Modane. Ces travaux pionniers ont ensuite été approfondis dans la soufflerie S3Ch de Meudon de manière à élaborer une base de données complète du buffet 2D sur une aile 2D en régime turbulent, que nous décrivons. Cette base de données a été utilisée de façon extensive, à l’ONERA et dans d’autres institutions pour valider différents outils de simulation, ces derniers étant alors utilisés à leur tour pour étudier la physique du buffet. Nous illustrons cette collaboration entre la simulation et la physique en rappelant qu'une analyse de stabilité linéaire de solutions précises des équations de Navier-Stokes moyennées au sens de Reynolds (RANS) a permis de prouver que le buffet 2D provient d'un mécanisme d'instabilité globale. Nous passons également en revue des essais plus récents réalisés dans la soufflerie S3Ch sur le cas d'une aile 2D laminaire qui révèlent des comportements très distincts par rapport au cas turbulent. Cela illustre la sensibilité du buffet à la nature de la couche limite. Le dernier paragraphe du document donne un bref aperçu des simulations avancées de ces différents cas tests. Dans la conclusion, nous énumérons les perspectives de recherche sur le sujet, qui incluent aussi des thématiques méthodologiques plus générales telles que l'assimilation de données

Impact assessment of an education course on vaccinations in a population of pregnant women: A pilot study

Introduction. Although the benefits of vaccinations have been extensively demonstrated, vaccination coverage remains unsatisfactory as result of many people's poor knowledge and negative perception of vaccination. We evaluated the impact of an education course on vaccinations in a population of pregnant women. Methods. A total of 214 pregnant women were invited to participate in this project, which was undertaken at the Obstetrics and Gynaecology Department of Careggi University Hospital in Florence (Italy). Anonymous questionnaires were administered to women before and after the intervention. A descriptive and statistical analysis was carried out in order to compare the responses obtained before and after the intervention. Results. Adherence to the initiative was good (98%): Initially, the respondents were not hostile to vaccinations, though many (43%) were poorly or insufficiently informed. The educational intervention had a positive impact. After the intervention, the number of women who rated their level of knowledge of vaccinations as poor or insufficient had decreased by 30% and the number of "hesitant" respondents had decreased with respect to all aspects of the study, especially the decision to be vaccinated during pregnancy. Conclusions. Hesitancy stems from a lack of accurate information. Healthcare professionals need to improve their communication skills. Appropriate education during pregnancy, when women are more receptive, may have a highly positive impact. These observations need to be considered in the planning of courses to prepare pregnant women for delivery also in other maternal-foetal centres in Italy

Environmental influences predominate in remission from alcohol use disorder in young adult twins

Background. Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission