On the Inner Horizon Instability of Non-Singular Black Holes

Regular black holes represent a conservative model in which the classical singularity is replaced by a non-singular core without necessarily modifying the spacetime outside the trapping horizon. Given the possible lack of phenomenological signatures, it is crucial to study the consistency of the model. In this short work, we review the physical mechanism leading to the instability of the central core, arguing that that non-perturbative backreation is non-negligible and must be taken into account to provide a meaningful description of physical black holes

Inner horizon instability and the unstable cores of regular black holes

Regular black holes with nonsingular cores have been considered in several approaches to quantum gravity, and as agnostic frameworks to address the singularity problem and Hawking’s information paradox. While in a recent work we argued that the inner core is destabilized by linear perturbations, opposite claims were raised that regular black holes have in fact stable cores. To reconcile these arguments, we discuss a generalization of the geometrical framework, originally applied to Reissner-Nordtsröm black holes by Ori, and show that regular black holes have an exponentially growing Misner-Sharp mass at the inner horizon. This result can be taken as an indication that stable nonsingular black hole spacetimes are not the definitive endpoint of a quantum gravity regularization mechanism, and that nonperturbative backreation effects must be taken into account in order to provide a consistent description of the quantum-gravitational endpoint of gravitational stellar collapse

Laparoscopic distal pancreatectomy in Italy: A systematic review and meta-analysis

Background The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed. Data Source A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs). Results From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status. Conclusions LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy

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

Natural and CVD type diamond detectors as dosimeters in hadrontherapy applications

Abstract Diamond is potentially a suitable material for use as radiation dosimeter; the wide band gap results in low dark currents and low sensitivity to visible light, the high carrier mobility can give rapid response, the very high density of strong bonds in the crystal structure make diamond very resistent to radiation damage; moreover it is tissue equivalent. The more recent advances in the synthesis of polycrystalline diamond by chemical vapour deposition (CVD) techniques have allowed the synthesis of material with electronic properties suitable for dosimetric application. In this paper we will report the results obtained in the study of the response of a natural diamond dosimeter and a CVD one irradiated with 62 AMeV proton beams to demonstrate their possible application in protontherapy

Immunoscintigraphy for Therapy Decision Making and Follow-Up of Biological Therapies

With the availability of new biological therapies there is the need of more accurate diagnostic tools to non-invasively assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients affected by cancer and other pathological conditions

lba14_prthe hoboe 2 multicenter randomized phase iii trial in premenopausal patients with hormone receptor positive early breast cancer comparing triptorelin plus either tamoxifen or letrozole or letrozole zoledronic acid

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On the viability of regular black holes

The evaporation of black holes raises a number of conceptual issues, most of them related to the final stages of evaporation, where the interplay between the central singularity and Hawking radiation cannot be ignored. Regular models of black holes replace the central singularity with a nonsingular spacetime region, in which an effective classical geometric description is available. It has been argued that these models provide an effective, but complete, description of the evaporation of black holes at all times up to their eventual disappearance. However, here we point out that known models fail to be self-consistent: the regular core is exponentially unstable against perturbations with a finite timescale, while the evaporation time is infinite, therefore making the instability impossible to prevent. We also discuss how to overcome these difficulties, highlighting that this can be done only at the price of accepting that these models cannot be fully predictive regarding the final stages of evaporation

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability

Objective. The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. Method. In a multicenter study, a phantom with spheres of different diameters (6.5–57.4 mm) was filled with 18F-FDG at different target-to-background ratios (TBR: 2.5–70) and scanned for different acquisition periods (2–5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. Results. The goodness of the model fit was high (R2: 0.74–0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. Conclusions. Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration