CP Violation in the SUSY Seesaw: Leptogenesis and Low Energy

We suppose that the baryon asymmetry is produced by thermal leptogenesis (with flavour effects), at temperatures $\sim 10^{9} - 10^{10}$ GeV, in the supersymmetric seesaw with universal and real soft terms. The parameter space is restricted by assuming that $l_\alpha \to l_\beta \gamma$ processes will be seen in upcoming experiments. We study the sensitivity of the baryon asymmetry to the phases of the lepton mixing matrix, and find that leptogenesis can work for any value of the phases. We also estimate the contribution to the electric dipole moment of the electron, arising from the seesaw, and find that it is (just) beyond the sensitivity of next generation experiments (\lsim 10^{-29} e cm). The fourteen dimensional parameter space is efficiently explored with a Monte Carlo Markov Chain, which concentrates on the regions of interest.Comment: 30 pages, 7 figure

Insensitivity of flavoured leptogenesis to low energy CP violation

If the baryon asymmetry of the Universe is produced by leptogenesis, CP violation is required in the lepton sector. In the seesaw extension of the Standard Model with three hierarchical right-handed neutrinos, we show that the baryon asymmetry is insensitive to the PMNS phases: thermal leptogenesis can work for any value of the observable phases. This result was well-known when there are no flavour effects in leptogenesis; we show that it remains true when flavour effects are included.Comment: 4 pages, 1 figure; version accepted for publication, added explanations, notation clarifie

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer

Cancer stem cell metabolism

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets

Various definitions of Minimal Flavour Violation for Leptons

Neutrino masses imply the violation of lepton flavour and new physics beyond the Standard Model. However, flavour change has only been observed in oscillations. In analogy with the quark sector, we could deduce the existence of a principle of Minimal Flavour Violation also for Leptons. Such an extension is not straightforward, since the mechanisms generating neutrino masses are unknown and many scenarios can be envisaged. Thus, we explore some possible definitions of MFVL and propose a notion that can include many models. We build an R-parity violating neutrino mass model in agreement with our preferred definition of MFVL, and show that flavour violating processes are not neccessarily controlled by the MNS mixing matrix

Studies on the lepton mixing matrix and dark matter

Les oscillations des neutrinos et la matière noire sont deux évidences expérimentales importantes d une physique au-delà du Modèle Standard. Les oscillations des neutrinos impliquent l'existence d'une matrice de mélange leptonique, qui peut contribuer aux processus de violation de la saveur et de violation de la symétrie CP à une échelle d'énergie accessible aux prochaines expériences, et à la violation de CP à très haute énergie, ingrédient nécessaire pour expliquer l'asymétrie baryonique de l'Univers. Avec un point de vue phénoménologique, nous avons formulé une possible définition de violation minimale de la saveur chez les leptons et nous avons étudié les relations entre la violation de CP responsable de l asymétrie baryonique de l Univers et les phases de la matrice de mélange leptonique. Nous nous sommes également intéressés aux différents mécanismes de production de la matière noire, en particulier dans le cadre de la désintegration des particules scalaires chargéesNeutrino oscillations, the baryon asymmetry and dark matter are important evidences of new physics beyond the Standard Model. Neutrino oscillations imply neutrino masses and a lepton mixing matrix that can contribute to flavour violating processes and CP violation at low energies, accessible to next experiments, and to the CP violation necessary for baryogenesis. With a phenomenological point of view, we have proposed a definition of minimal flavour violation for leptons and we have studied the relations between the CP violation necessary to explain the baryon asymmetry of the Universe and the low energy phases of the leptonic mixing matrix. In relation to dark matter, we have studied different mechanisms of dark matter production through the decay of a charged long-lived scalar particleLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Measurements of temperature increase induced on a tissue-mimicking material by a clinical US-guided HIFU system

A framework for the evaluation of temperature increase in a tissue-mimicking material (TMM) induced by a clinical Ultrasound-guided High Intensity Focused Ultrasound (US-guided HIFU) system was developed. HIFU procedures are minimally invasive treatments that achieve deep tumor ablation, with the sparing of normal tissues, through thermal or mechanical effects induced by a HIFU beam generated with a focused transducer. Temperature evaluation is therefore crucial for the assurance of patient safety and treatment effectiveness. Nevertheless, it is a very difficult task on the US-guided systems, where high-pressure fields are involved. As far as we know, this study is the first attempt of temperature evaluation on a clinical US-guided HIFU system. Temperature evaluation was performed at typical clinical settings (between 80 W and 400 W, for 3s sonications) by the use of needle thermocouples connected to a voltmeter and inserted in a polyacrylamide gel phantom, prepared in-house to reproduce soft tissue behavior. Data sampling was performed with the use of acquisition software developed with LabView, while US-imaging was used to verify the position of the thermocouple. Typical rising curves of temperature were recovered, and rapid decrease was found when the HIFU field turned off. The highest temperature increases were concentrated inside the geometrical focus and were higher than 55 Celsius degrees at all power outputs. Repetition of measurements was not possible after sonications at the highest power outputs (400W). The absolute temperature of 98 Celsius degrees was never exceeded

Vitamin D Supplementation and Cancer Mortality: Narrative Review of Observational Studies and Clinical Trials

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association

Local dose analysis to predict acute and late urinary toxicities after prostate cancer radiotherapy: Assessment of cohort and method effects

International audiencePURPOSE:To perform bladder dose-surface map (DSM) analysis for (1) identifying symptom-related sub-surfaces (Ssurf) and evaluating their prediction capability of urinary toxicity, (2) comparing DSM with dose-volume map (DVM) (method effect), and (3) assessing the reproducibility of DSM (cohort effect).METHODS AND MATERIALS:Urinary toxicities were prospectively analyzed for 254 prostate cancer patients treated with IMRT/IGRT at 78/80 Gy. DSMs were generated by unfolding bladder surfaces in a 2D plane. Pixel-by-pixel analysis was performed to identify symptom-related Ssurf. Likewise, voxel-by-voxel DVM analysis was performed to identify sub-volumes (Svol). The prediction capability of Ssurf and Svol DVHs was assessed by logistic/Cox regression using the area under the ROC curve (AUC). The Ssurf localization and prediction capability were compared to (1) the Svol obtained by DVM analysis in the same cohort and (2) the Ssurf obtained from other DSM studies.RESULTS:Three Ssurf were identified in the bladder: posterior for acute retention (AUC = 0.64), posterior-superior for late retention (AUC = 0.68), and inferior-anterior-lateral for late dysuria (AUC = 0.73). Five Svol were identified: one in the urethra for acute incontinence and four in the posterior bladder part for acute and late retention, late dysuria, and hematuria. The overlap between Ssurf and Svol was moderate for acute retention, good for late retention, and bad for late dysuria, and AUCs ranged from 0.62 to 0.81. The prediction capabilities of Ssurf and Svol models were not significantly different. Among five symptoms comparable between cohorts, common Ssurf was found only for late dysuria, with a good spatial agreement.CONCLUSION:Spatial agreement between methods is relatively good although DVM identified more sub-regions. Reproducibility of identified Ssurf between cohorts is low

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results