Time-dependent modeling of TeV-detected, young pulsar wind nebulae

The increasing sensitivity of instruments at X-ray and TeV energies have revealed a large number of nebulae associated with bright pulsars. Despite this large data set, the observed pulsar wind nebulae (PWNe) do not show a uniform behavior and the main parameters driving features like luminosity, magnetization, and others are still not fully understood. To evaluate the possible existence of common evolutive trends and to link the characteristics of the nebula emission with those of the powering pulsar, we selected a sub-set of 10 TeV detections which are likely ascribed to young PWNe and model the spectral energy distribution with a time-dependent description of the nebulae's electron population. In 9 of these cases, a detailed PWNe model, using up-to-date multiwavelength information, is presented. The best-fit parameters of these nebula are discussed, together with the pulsar characteristics. We conclude that TeV PWNe are particle-dominated objects with large multiplicities, in general far from magnetic equipartition, and that relatively large photon field enhancements are required to explain the high level of Comptonized photons observed. We do not find significant correlations between the efficiencies of emission at different frequencies and the magnetization. The injection parameters do not appear to be particularly correlated with the pulsar properties either. We find that a normalized comparison of the SEDs (e.g., with the corresponding spin-down flux) at the same age significantly reduces the spectral distributions dispersion.Comment: 38 pages, 20 figures, 8 tables. Accepted for publication in the Journal of High Energy Astrophysics (JHEAp

Is there room for highly magnetized pulsar wind nebulae among those non-detected at TeV?

We make a time-dependent characterization of pulsar wind nebulae (PWNe) surrounding some of the highest spin-down pulsars that have not yet been detected at TeV. Our aim is assessing their possible level of magnetization. We analyze the nebulae driven by J2022+3842 in G76.9+1.0, J0540-6919 in N158A (the Crab twin), J1400--6325 in G310.6--1.6, and J1124--5916 in G292.0+0.18, none of which have been found at TeV energies. For comparison we refer to published models of G54.1+0.3, the Crab nebula, and develop a model for N157B in the Large Magellanic Cloud (LMC). We conclude that further observations of N158A could lead to its detection at VHE. According to our model, a FIR energy density of 5 eV cm$^{-3}$ could already lead to a detection in H.E.S.S. (assuming no other IC target field) within 50 hours of exposure and just the CMB inverse Compton contribution would produce VHE photons at the CTA sensitivity. We also propose models for G76.9+1.0, G310.6--1.6 and G292.0+1.8 which suggest their TeV detection in a moderate exposure for the latter two with the current generation of Cherenkov telescopes. We analyze the possibility that these PWNe are highly magnetized, where the low number of particles explains the residual detection in X-rays and their lack of detection at TeV energies.Comment: Accepted for publication in MNRA

The effects of magnetic field, age, and intrinsic luminosity on Crab-like pulsar wind nebulae

We investigate the time-dependent behavior of Crab-like pulsar wind nebulae (PWNe) generating a set of models using 4 different initial spin-down luminosities ($L_0 =\{1,0.1,0.01,0.001\} \times L_{0, {\rm Crab}}$), 8 values of magnetic fraction ($\eta =$ 0.001, 0.01, 0.03, 0.1, 0.5, 0.9, 0.99, and 0.999, i.e., from fully particle dominated to fully magnetically dominated nebulae), and 3 distinctive ages: 940, 3000, and 9000 years. We find that the self-synchrotron Compton (SSC) contribution is irrelevant for $L_{SD}$=0.1, 1, and 10% of the Crab power, disregarding the age and the magnetic fraction. SSC only becomes relevant for highly energetic ($\sim 70$ of the Crab), particle dominated nebulae at low ages (of less than a few kyr), located in a FIR background with relatively low energy density. Since no pulsar other than Crab is known to have these features, these results clarify why the Crab Nebula, and only it, is SSC dominated. No young PWN would be detectable at TeV energies if the pulsar's spin-down power is 0.1% Crab or lower. For 1% of the Crab spin-down, only particle dominated nebulae can be detected by H.E.S.S.-like telescopes when young enough (with details depending on the precise injection and environmental parameters). Above 10% of the Crab's power, all PWNe are detectable by H.E.S.S.-like telescopes if they are particle dominated, no matter the age. The impact of the magnetic fraction on the final SED is varied and important, generating order of magnitude variations in the luminosity output for systems that are otherwise the same (equal $P$, $\dot P$, injection, and environment).Comment: Accepted for publication in MNRA

Meeting patient expectations in migraine treatment: what are the key endpoints?

Clinical outcomes of migraine treatment are generally based on two major endpoints: acute pain resolution and effects on quality of life (QOL). Resolution of acute pain can be evaluated in a number of ways, each increasingly challenging to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF plus no adverse events (SNAE, the most challenging). QOL questionnaires help assess the burden of migraine and identify optimal treatments. Pain resolution and improved QOL form the basis of the ultimate target-meeting patient expectations, to achieve patient satisfaction. To achieve this, it is crucial to choose appropriate endpoints that reflect realistic treatment goals for individual patients. Moreover, SNAE can help discriminate between triptans, with almotriptan having the highest SNAE score. Kaplan-Meier plots are also relevant when evaluating migraine treatments. The use of symptomatic medication may lead to the paradoxical development of medication-overuse headache. In general practice, patients should use simple tools for pain measurement (e.g. headache diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL restoration would constitute a step forward in migraine management

Decision Support System for target prostate biopsy outcome prediction: Clustering and FP-growth algorithm for fuzzy rules extraction

An automated and data-driven rules extraction is crucial for the construction of Fuzzy Inference Systems (FIS). This work presents a method for extracting fuzzy rules based on clustering and association mining through the FP-growth algorithm. First, Self Organizing Maps are used to identify subsets of elements with similar characteristics, separately for each class. Then, the FP-Growth algorithm is applied to each cluster. Elements matching each rule are subdivided in the corresponding classes and only rules showing a predominance of elements belonging to one class are used as fuzzy rules. The method was applied to the construction of a Decision Support System based on FIS for the target prostate biopsy outcome prediction based on six pre-bioptic variables. A dataset containing 1447 patients (824 with positive outcome, 623 with negative outcome) was used. Four and six clusters were identified for the positive and the negative class, respectively. A total of 151 rules were extracted with FP-Growth algorithm and 29 were included in the FIS. The system was able to classify 927 patients out of 1447. On the classi-fied subjects, it reached a sensitivity of 87.5% and a specificity of 58.8%

Large-scale plant production of lycium barbarum l. By liquid culture in temporary immersion system and possible application to the synthesis of bioactive substance

Goji (Lycium barbarum L.) has recognized nutritive and antioxidant properties and many products are commercialized for health in food market. Besides its food use, goji has been the subject of more than 2000 years of traditional Chinese medicine, using berries, root bark, and leaves. Here, the potential of the liquid culture in temporary immersion system (TIS) by using the bioreactor Plantform™ was tested for the large-scale production of high-quality goji shoots and the subsequent production of total phenols and flavonoids. The three tested immersion cycles differently influenced the shoot quality in terms of proliferation and hyperhydricity. The best immersion cycle (time and frequency) was proven to have the shortest daily immersion time (6 min every 24 h) which ensured good levels of relative growth and multiplication rate, very limited onset of hyperydricity, and the longest shoots, promoting direct rooting after only 30 days of culture. In comparison with the semisolid culture, the TIS culture resulted in an increase of the total phenolic content (TPC) and in a lower value of the total flavonoid content (TFC). However, considering the higher quantity of biomass produced in the Plantform™ bioreactor, the difference in terms of TFC productivity between semisolid medium and TIS liquid culture was proven to be statistically equivalent

Magna Graecia transcatheter aortic valve implantation registry: data on contrast medium osmolality and postprocedural acute kidney injury

A comprehensive description of baseline characteristics, procedural features and outcomes related to the development of acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is reported in our research paper (Impact of contrast medium osmolality on the risk of acute kidney injury after transcatheter aortic valve implantation: insights from the Magna Graecia TAVI registry. Int J Cardiol. DOI: 10.1016/j.ijcard.2020.12.049). Three Italian heart centers were involved in this multicentric observational study. Between March 2011 and February 2019, a total of 888 patients underwent TAVI; according to the inclusion and exclusion criteria, 697 patients were included in the post-hoc analysis. This Data in Brief paper aims to report demographic, clinical, laboratory, echocardiographic, intraprocedural, periprocedural, postprocedural and follow-up data; all of them were prospectively collected from each patient's health record, whereas the analysis was performed retrospectively. Targets of this data analysis were: 1) to evaluate the impact of contrast medium (CM) osmolality on TAVI-related AKI; 2) to identify the most of risk factors involved in the development of such complication, and consequently in the occurrence of 1-year mortality; 3) to estimate the impact of CM osmolality on AKI in specific patient subgroups

Impact of contrast medium osmolality on the risk of acute kidney injury after transcatheter aortic valve implantation: insights from the Magna Graecia TAVI registry

Background: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is frequent and associated with adverse outcomes and mortality; to date, in such setting of patients there is no consistent evidence that either low-osmolar contrast media (LOCM) or iso‐osmolar contrast medium (IOCM) are superior to the other in terms of renal safety. Methods: 697 consecutive patients not in hemodialysis treatment who underwent TAVI (327 males, mean age 81.01 ± 5.75 years, mean european system for cardiac operative risk evaluation II 6.17 ± 0.23%) were enrolled. According to osmolality of the different iodinated CM, the population was divided in 2 groups: IOCM (n = 370) and LOCM group (n = 327). Preoperatively, 40.54% of patients in IOCM vs 39.14% in LOCM group (p = 0.765) suffered from chronic kidney disease (CKD). Results: The incidence of AKI was significantly lower with IOCM (9.73%) than with LOCM (15.90%; p = 0.02), and such significant difference (p < 0.001) in postprocedural change of renal function parameters persisted at discharge too. The incidence of AKI was also significantly lower with IOCM in younger patients, without diabetes, anemia, coronary artery disease history, CKD, chronic or persistent atrial fibrillation, left ventricular ejection fraction ≤35%, and in patients with low operative mortality risk scores, receiving lower amounts of dye (p < 0.05 for all). Importantly, multivariate analysis identified LOCM administration as an independent risk factor for both AKI (p = 0.006) and 1-year mortality (p = 0.001). Conclusions: The use of IOCM have a favorable impact on renal function with respect to LOCM, but it should be considered especially for TAVI patients at lower AKI risk

Crown Detectors to Observe Horizontal and Upward Air-Showers

Cerenkov Telescopes and Scintillators set on a Crown-like arrays facing the Horizons may reveal far Cosmic Rays Showers, nearer Anti-Neutrino-Electron + Electron --> W- shower in air and upgoing Tau Neutrino + N--> tau + X, --> Shower, Earth-Skimming tau air-showers. Even UHE SUSY Chi + e--> Selectron--> Chi + e at tens PeVs-EeV energy may blaze at Horizons, as anti-neutrino electron at Glashow peak - Burst shower. We show first estimate on down and up-going Horizontal Showers traces for present and future Magic-like Crown Arrays and their correlated Scintillator-like twin Crown Arrays. The one mono or stereo-Magic elements facing the Horizons are already comparable to present Amanda underground neutrino detector.Comment: 11 pages, 5 figures, COSPAR 200

Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer

Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa