In-Situ Particle Acceleration in Extragalactic Radio Hot Spots: Observations Meet Expectations

We discuss, in terms of particle acceleration, the results from optical VLT observations of hot spots associated with radio galaxies. On the basis of observational and theoretical grounds, it is shown that: 1. relatively low radio-radio power hot spots are the optimum candidates for being detected at optical waves. This is supported by an unprecedented optical detection rate of 70% out of a sample of low radio power hot spots. 2. the shape of the synchrotron spectrum of hot spots is mainly determined by the strength of the magnetic field in the region. In particular, the break frequency, related to the age of the oldest electrons in the hot spots, is found to increase with decreasing synchrotron power and magnetic field strength. Both observational results are in agreement with an in-situ particle acceleration scenario.Comment: 5 pages, TeX (or Latex, etc), 4 figures, to appear in MNRAS Letter, Updated reference

THE ROLE OF THE B CELL ANTIGEN RECEPTOR IN A MOUSE MODEL OF NON-HODGKIN LYMPHOMA

The B cell antigen receptor (BCR) plays a central role both in early B-cell development and in mature B cells, where it controls survival and allows the organism to mount protective immune responses against foreign antigens. Surface BCR expression is retained in most types of Non-Hodgkin B-cell lymphomas (NHL), where it has been proposed to participate to tumor initiation, maintenance and progression. This study has provided for the first time an in vivo genetic proof for the role of the BCR in B-cell lymphomagenesis. Using the \u3bb-MYC Burkitt lymphoma (BL) mouse model, in which conditional ablation of the BCR can be induced in c-MYC transformed B cells through the Cre/loxP recombination system, I provide evidence for the essential role of the BCR in tumor maintenance. Acute BCR ablation in \u3bb-MYC lymphomas delayed cell cycle progression and augmented apoptosis, causing the rapid disappearance of BCR- tumor cells when these cells were grown both in vitro and in vivo in competition with their BCR+ counterparts. Similar results were obtained using the human Burkitt lymphoma cell line, RAMOS. This study has also elucidated crucial effectors of tonic BCR signalling that influence the survival and growth of BL cells. BCR inactivation led to a reduction in GSK3\u3b2 phosphorylation, leading to an increase in its enzymatic activity. Importantly, treatment of lymphoma cells with a GSK3\u3b2 small molecule inhibitor restored the ability of BCR-deficient lymphomas to compete with their BCR+ counterparts. I could also show that c-MYC transformed B cells acquired exquisite sensitivity to the mTOR inhibitor rapamycin upon BCR inactivation. Using a combination of quantitative proteome and whole transcriptome analyses we have started to shed light on the contribution of the BCR to the maintenance of c-MYC transformed B cells. In \u3bb-MYC lymphomas, the BCR regulated a substantial number of MYC targets genes. Notably, the majority of these shared targets were normalized in BCR- tumor cells upon pharmacological inhibition of GSK3\u3b2. These result point to the tempting hypothesis that the BCR supports MYC-driven lymphomagenesis, by the inhibition of GSK3\u3b2-mediated phosphorylation and hence degradation of c-MYC protein. Finally, our study demonstrates that the failure of c-MYC transformed B cells to grow in vivo is strictly dependent on the concomitant presence of their BCR+ counterparts. This result has important implications for the design of clinical trials limited to the use of inhibitors of the BCR signalling pathway for the treatment of BL and other forms of aggressive NHL. To avoid the outgrowth of BCR- escape variants in response to such treatments, we propose the integration in the therapeutic protocol of the mTOR inhibitor rapamacyin that showed high efficacy in the killing Ig receptor-less lymphoma cells

Chandra detection of the radio and optical double hot spot of 3C 351

In this letter we report a Chandra X-ray detection of the double northern hot spot of the radio quasar 3C 351. The hot spot has also been observed in the optical with the Hubble Space Telescope (R-band) and with the 3.5m. Telescopio Nazionale Galileo (B-band). The radio-to-optical and X-ray spectra are interpreted as the results of the synchrotron and synchrotron-self-Compton (SSC) mechanisms, respectively, with hot-spot magnetic field strengths ~3 times smaller than the equipartition values. In the framework of shock acceleration theory, we show that the requirement for such a relatively small field strength is in agreement with the fitted synchrotron spectral models and with the sizes of the hot spots. Finally, we show that the combination of a lower magnetic field strength with the high frequencies of the synchrotron cut-off in the fitted synchrotron spectra provides strong evidence for electron acceleration in the hot spots.Comment: 16 pag. + 2 .PS figures (fig.2 color), ApJ Letter in pres

Laser thermal ablation to treat a recurrent soft-tissue sarcoma of the leg : A case report

We present the case of a 52-year-old male patient with recurrence of a soft-tissue sarcoma of the left leg treated with percutaneous laser ablation. The patient received the diagnosis of sarcoma for the first time in 2011; further local recurrences and a pulmonary metastatic spread occurred during follow-up, so the patient has been treated several times with chemotherapy, limb-sparing surgery and radiotherapy. In September 2017, a new local recurrence of sarcoma occurred, for which limb amputation was proposed but refused by the patient. Laser ablation with ultrasound guidance was performed, with complete ablation at 6 months and limb salvage

Image-guided laser ablation in the treatment of recurrence of renal tumours : technique and preliminary results

Abdominal recurrences of renal cell carcinoma (RCC) after surgery might represent a challenge for treatment, often requiring difficult surgeries or anticipated systemic therapy. Our aim is to illustrate a novel application of laser ablation for the treatment of abdominal recurrences of RCC. Patients with abdominal recurrences of renal cancer were treated under ultrasound/computed tomography guidance with a diode laser inserted into the lesion through a thin 21-G needle. A fixed 3-W power protocol was used, changing the illumination time according to lesion dimension and shape. Also, technical success, technical efficacy, local tumour progression, and major and minor complications were retrospectively analysed. Three patients were treated with image-guided laser ablation for abdominal recurrences of RCC. In all cases, it was possible to perform ablation as preoperatively planned and all three nodules (size of 6, 8, and 12 mm) were completely ablated with no evidence of residual enhancement after 6 weeks at contrast-enhanced CT. No minor or major complications were observed. No local tumour progression was reported up to 12 months from ablation. Image-guided laser ablation holds the potential to offer a minimally invasive treatment to patients with abdominal recurrence of RCC. Further studies are needed to evaluate the clinical role of this technique

Pancreatic ablation : minimally invasive treatment options

Despite the significant improvement of knowledge and technologies in tumor treatments, pancreatic tumor remains a complex disease still characterized by a poor prognosis. The increasing role of minimally invasive techniques started to drive the effort of scientific medicine to evaluate the possibilities of application of these techniques to pancreatic cancer. The purpose of this paper is to present a brief summary of the different ablative techniques available and proposed for pancreatic tumor treatment considering invasive, noninvasive, thermal and non-thermal techniques

Ultrasound and cone beam CT fusion for liver ablation : technical note

Purpose: To assess the feasibility of fusion imaging between intraprocedural ultrasound (US) and contrast-enhanced cone-beam CT (CBCT) for small (< 2 cm) hepatocellular carcinoma (HCC). Materials and methods: Six patients (five males, one female, age range 58\u201380, mean 69 years), with small (mean diameter 16.8 mm) HCC poorly visible at US underwent percutaneous microwave ablation under US/CBCT fusion guidance. During general anesthesia with apnea control, a contrast- enhanced CBCT was acquired with an active tracker. Subsequently, real time US images were fused with CBCT images, and treatment performed under fusion imaging guidance. Feasibility of fusion imaging and percutaneous ablation were assessed, correct targeting (distance from center of tumor and center of ablation area <5 mm) and one-month primary technical efficacy were evaluated. Major and minor complications as well as overall procedural time were recorded. Results: US/CBCT fusion was feasible in all cases, allowing for completion of the treatment as previously planned (technical success 100%). Correct targeting was achieved in 4/6 cases (66%), while in two cases, center of tumor and center of ablated area were respectively 7 and 8 mm distant. At 1 month CT scan, all tumors were completely ablated (primary technical efficacy 100%). No major or minor complications occurred. Mean overall procedure time was 127 min. Conclusions: US/CBCT fusion is a feasible technique for liver ablation, and might represent a useful tool to increase the correct targeting of poorly US-visible HCC nodules in the angio suite

Left atrial trajectory impairment in hypertrophic cardiomyopathy disclosed by geometric morphometrics and parallel transport

The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction

OLIMPIC : a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV). Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab. Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22\u201385 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03\u2013124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55\u2013513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39\u2013222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1\u20139. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively. Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings. Trial registration: www.ClinicalTrials.Gov (NCT No: NCT02034006)

Focused ultrasound : tumour ablation and its potential to enhance immunological therapy to cancer

Various kinds of image-guided techniques have been successfully applied in the last years for the treatment of tumours, as alternative to surgical resection. High intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image-guided technique that allows for achieving tissue destruction with the application of focused ultrasound at high intensity. This technique has been successfully applied for the treatment of a large variety of diseases, including oncological and non-oncological diseases. One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected \u201csystemic\u201d response to treatments designed to be \u201clocal\u201d. In the present article the mechanisms of action of HIFU are described, and the main clinical applications of this technique are reported, with a particular focus on the immune-stimulation process that might originate from tumour ablations