Quantum Vacuum Excitation of a Quasinormal Mode in an Analog Model of Black Hole Spacetime.

Vacuum quantum fluctuations near horizons are known to yield correlated emission by the Hawking effect. We use a driven-dissipative quantum fluid of microcavity polaritons as an analog model of a quantum field theory on a black-hole spacetime and numerically calculate correlated emission. We show that, in addition to the Hawking effect at the sonic horizon, quantum fluctuations may result in a sizable stationary excitation of a quasinormal mode of the field theory. Observable signatures of the excitation of the quasinormal mode are found in the spatial density fluctuations as well as in the spectrum of Hawking emission. This suggests an intrinsic fluctuation-driven mechanism leading to the quantum excitation of quasinormal modes on black hole spacetimes.

Lack of association between obesity and aggressiveness of differentiated thyroid cancer.

PURPOSE: Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort. METHODS: Patients with DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score. RESULTS: The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman's ρ - 0.02; p = 0.71) and ATA Initial Risk Stratification System score (ρ 0.03; p = 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate-high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06). CONCLUSIONS: Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.

Thyroid nodule recurrence following lobo-isthmectomy: incidence, patient's characteristics, and risk factors.

PURPOSE: This study was aimed at assessing the incidence and timing of thyroid nodules recurrence, defined as appearance of new benign or malignant nodules in contralateral lobe in patients with benign thyroid nodules or thyroid microcarcinoma treated with lobo-isthmectomy. Patient's characteristics and risk factors associated with this phenomenon were also investigated. METHODS: A retrospective study was performed by evaluating 413 patients undergoing lobo-isthmectomy with a minimum follow-up of 1 year. Clinical characteristics, surgical interventions and complications, histological diagnosis, and thyroid function at last follow-up were collected. RESULTS: Single or multiple thyroid nodule recurrence equally occurred in 80 patients (23%) with a median time to relapse of ~ 5 years (range 0.3-34.5 years) after lobo-isthmectomy. Recurrence was significantly associated with younger age (< 46 years) and number of pregnancies in women. Development of hypothyroidism was not rare either (~ 10%) and appeared in 3-19 months; a preoperative TSH level > 2.43 mIU/L was associated with the need of l-thyroxin replacement therapy after surgery. The most frequent surgical complication was transient hypoparathyroidism (4.6%), while the rate of permanent hypoparathyroidism significantly increased in patients submitted to completion thyroidectomy (5.3%). CONCLUSIONS: Thyroid nodules recurrence following lobo-isthmectomy is not a rare event and occurs within 5 years after surgery, more frequently in younger patients with family history of nodular goiter and in women with multiple pregnancies. Pre-surgical TSH levels may predict the development of post-surgical hypothyroidism, possibly improving the management of patients addressed to surgery.

Reduced expression of THRß in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression.

PURPOSE: Down-regulation of thyroid hormone receptor beta (THRß) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRß mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical-biological features. METHODS: Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRß gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRß. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart. RESULTS: THRß transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRß expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression. CONCLUSIONS: Our results demonstrate that down-regulation of THRß is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis.

Diagnostic accuracy and interobserver agreement of Quasistatic Ultrasound Elastography in the diagnosis of thyroid nodules.

PURPOSE: To assess the best technique and the diagnostic accuracy of Quasistatic Ultrasound Elastography (QUE) in thyroid nodules. Interobserver agreement was also evaluated. MATERIALS AND METHODS: A preliminary study of 50 patients with 54 thyroid nodules was performed with quantitative software in order to define the best cut-off value of different imaging methods. All patients underwent total thyroidectomy and histopathology findings served as the standard of reference. Thereafter, 154 nodules in 137 consecutive patients were prospectively evaluated by three operators. Findings at fine-needle aspiration cytology and histopathology (N = 60) served as the standard of reference. RESULTS: The most accurate technique was the axial peri-intranodular measurement method which achieved an area under the ROC curve of 0.961 (95 %CI 0.848 - 1.00) and had an optimal cut-off value of 3.00. QUE in the differentiation of thyroid nodules showed for operator 1: sensitivity 90 % (95 %CI 73.5 - 97.9 %), specificity 92.7 % (95 %CI 86.7 - 96.6 %), LR+ 12.40 (6.54 - 23.50), LR- 0.11 (0.04 - 0.32) and accuracy 91.4 % (95 %CI 85.4 - 97.3 %); for operator 2: sensitivity 86.7 % (95 %CI 69.3 - 96.2 %), specificity 87.1 % (95 %CI 79.9 - 92.4 %), LR+ 6.72 (4.16 - 10.80), LR- 0.15 (0.06 - 0.38) and accuracy 86.9 % (95 %CI 80.0 - 93.7 %); for operator 3: sensitivity 80 % (95 %CI 61.4 - 92.3 %), specificity 83.9 % (95 %CI 76.2 - 89.9 %), LR+ 4.96 (3.20 - 7.70), LR- 0.24 (0.12 - 0.49) and accuracy 81.9 % (95 %CI 74.0 - 89.9 %). Interobserver agreement values between operator 1 and operator 2 (k = 0.79) (p < 0.05, 95 %CI 0.684 - 0.904), between operator 1 and operator 3 (k = 0.73, 95 %CI: 0.607 - 0.854) and between operator 2 and operator 3 (k = 0.71, 95 %CI: 0.584 - 0.835) were significant. CONCLUSION: QUE provides accurate quantitative evaluation of thyroid nodules with low interobserver variability.

The EGFR-mTOR pathway and laryngeal cancer angiogenesis.

Epidermal growth factor receptor (EGFR) is a trans-membrane tyrosine kinase taking part in cell transformation and tumor progression. One of the downstream pathways controlled by EGFR involves the mammalian target of rapamycin (mTOR), a proto-oncogene activated in several cell functions. Recent evidence seems to confirm that both EGFR and mTOR regulate angiogenesis. The aim of this study was to investigate the expression of EGFR and mTOR in laryngeal squamous cell carcinoma (LSCC) cells in a retrospective clinical setting and their correlation with tumor neo-angiogenesis, judged on the grounds of CD105-assessed microvascular density (MVD), and prognosis. We considered 76 consecutive patients with LSCC treated with surgery alone. Immunohistochemical expressions of EGFR, mTOR, and CD105 were measured using image analysis and findings underwent statistical analysis using univariate and multivariate models. We found that nodal status correlated significantly with patient prognosis in terms of disease-free survival (DFS) (p = 0.01). There was a strong direct correlation between mTOR and EGFR expression (p = 0.0003), and between mTOR and CD105-assessed MVD (p = 0.0025). Patients with a CD105-assessed MVD >5.28 % had a significantly higher recurrence rate (RR) (p = 0.026), and a significantly shorter DFS (p = 0.025). On multivariate analysis, only N stage [hazard ratio (HR) 3.54, p = 0.009] and CD105-assessed MVD (HR 2.87, p = 0.027) maintained their independent prognostic significance in terms of DFS. Judging from our promising findings, the EGFR-mTOR pathway should be investigated further to understand its role in LSCC neo-angiogenesis.

An unusual subcutaneous breast cancer metastasis in a 86-year-old woman.

The most common metastasis site of breast cancer are the local and distant lymph nodes, bone, lungs, liver and brain. We report a 86-year-old woman with an unusual abdominal subcutaneous metastasis of breast cancer. The patient was diagnosed with invasive lobular breast cancer and had been treated six months earlier with modified radical mastectomy. Later she presented a painless mass on the middle upper abdominal wall. She was subsequently admitted to the hospital to perform a whole body CT scan, confirming the presence of the abdominal mass in epigastric region, causing a partial compression of the stomach. Histopathological studies confirmed that the abdominal mass was a rare subcutaneous metastatic lesion of breast origin. The patient underwent a surgical intervention to remove the metastasis and she recovered fully.

A novel approach to study oxidative stress in thyroid diseases: a preliminary study.

BACKGROUND AND OBJECTIVES: Recently, several Authors have emphasized the relationship between oxidative stress and thyroid tumors. Several methods have been proposed in the literature for the measurement of oxidative stress in human tissues, although the high reactivity and short half life of reactive oxygen and nitrogen species make difficult their direct determination. Here we propose a novel approach for the determination of oxidative stress in human tissues, taking into account the relationship between free radicals and thyroid diseases. MATERIALS AND METHODS: Our goal in this preliminary study, was to demonstrate the opportunity to use the coupling of the EPR-spin trapping technique with the hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine, to detect oxidative stress in the human blood of patients with thyroid disease. RESULTS: Our preliminary findings confirm that this is a sensible, precise and valid method to study the oxidative stress and encourage us to continue the project. CONCLUSIONS: Our next goal will be to enroll patients affected by different thyroid diseases and to study the effect of some antioxidants in the management of the disease. This will allow to better understand the pathological path that binds the formation of reactive oxidizing species to the thyroid cancer and eventually to take into account the antioxidant therapy, as a possible additional "therapeutic weapon".

Mediastinal parathyroid adenoma: a case report.

Ectopic parathyroid adenomas represent a diagnostic challenge, since they are quite rare in clinical practice. We present a case of a 61 years old man with symptomatic hypercalcemia due to an ectopic parathyroid adenoma in the upper-anterior mediastinum that was not localized by the scintigraphy. Ultrasonography identified a nodule on the left upper-superior lobe of the thyroid gland, consistent with a parathyroid adenoma; scintigraphy showed two focuses of abnormal tracer uptake, one on the left upper-superior lobe of the gland and the other on the right inferior lobe of the gland. Patient underwent surgery to remove the adenoma on the left side, but postoperatively PTH and serum calcium level were still elevated. CT scan showed a mass of 27 x 22 mm in the upper anterior mediastinum, in front of the right emisoma of D2. The final surgery allowed us to remove the adenoma with a laterocervical approach. The histopathology was consistent with parathyroid adenoma.

A high-resolution neutron spectroscopic camera for the SPARC tokamak based on the Jet European Torus deuterium-tritium experience.

Dedicated nuclear diagnostics have been designed, developed, and built within EUROFUSION enhancement programs in the last ten years for installation at the Joint European Torus and capable of operation in high power Deuterium-Tritium (DT) plasmas. The recent DT Experiment campaign, called DTE2, has been successfully carried out in the second half of 2021 and provides a unique opportunity to evaluate the performance of the new nuclear diagnostics and for an understanding of their behavior in the record high 14 MeV neutron yields (up to 4.7 × 1018 n/s) and total number of neutrons (up to 2 × 1019 n) achieved on a tokamak. In this work, we will focus on the 14 MeV high resolution neutron spectrometers based on artificial diamonds which, for the first time, have extensively been used to measure 14 MeV DT neutron spectra with unprecedented energy resolution (Full Width at Half Maximum of ≈1% at 14 MeV). The work will describe their long-term stability and operation over the DTE2 campaign as well as their performance as neutron spectrometers in terms of achieved energy resolution and high rate capability. This important experience will be used to outline the concept of a spectroscopic neutron camera for the SPARC tokamak. The proposed neutron camera will be the first one to feature the dual capability to measure (i) the 2.5 and 14 MeV neutron emissivity profile via the conventional neutron detectors based on liquid or plastics scintillators and (ii) the 14 MeV neutron spectral emission via the use of high-resolution diamond-based spectrometers. The new opportunities opened by the spectroscopic neutron camera to measure plasma parameters will be discussed.

New method for time alignment and time calibration of the TOFOR time-of-flight neutron spectrometer at JET.

The TOFOR time-of-flight (TOF) neutron spectrometer at the Joint European Torus (JET) is composed of 5 start (S1) and 32 stop (S2) scintillation detectors. Recently, the data acquisition system (DAQ) of TOFOR was upgraded to equip each of the 37 detectors with its own waveform digitizer to allow for correlated time and pulse height analysis of the acquired data. Due to varying cable lengths and different pulse processing pathways in the new DAQ system, the 160 (5 · 32) different TOF pairs of start-stop detectors must be time-aligned to enable the proper construction of a summed TOF spectrum. Given the time (energy) resolution required by the entire spectrometer system to measure different plasma neutron emission components, it is of importance to align the detector pairs to each other with sub-nanosecond precision. Previously, the alignment partially depended on using fusion neutron data from Ohmic heating phases of JET experimental pulses. The dependence on fusion neutron data in the time alignment process is, however, unsatisfactory as it involves data one would wish to include in an independent analysis for physics results. In this work, we describe a method of time-aligning the detector pairs by using gamma rays. Given the known geometry and response of TOFOR to gamma rays, the time alignment of the detector pairs is found by examining gamma events interacting in coincidence in both S1-S1 and S1-S2 detector combinations. Furthermore, a technique for separating neutron and gamma events in the different detector sets is presented. Finally, the time-aligned system is used to analyze neutron data from Ohmic phases for different plasma conditions and to estimate the Ohmic fuel ion temperature.

Forward modeling of pile-up events in liquid scintillator detectors for neutron emission spectroscopy.

When using liquid scintillator detectors to measure the neutron emission spectrum from fusion plasmas, the problem of pile-up distortion can be significant. Because of the large neutron rates encountered in many fusion experiments, some pile-up distortion can remain even after applying traditional pile-up elimination methods, which alters the shape of the measured light-yield spectrum and influences the spectroscopic analysis. Particularly, pile-up events appear as a high-energy tail in the measured light-yield spectrum, which obfuscates the contribution that supra-thermal ions make to the energy spectrum. It is important to understand the behavior of such "fast ions" in fusion plasmas, and it is hence desirable to be able to measure their contribution to the neutron spectrum as accurately as possible. This paper presents a technique for incorporating distortion from undetected pile-up events into the analysis of the light-yield spectrum, hence compensating for pile-up distortion. The spectral contribution from undetected pile-up events is determined using Monte Carlo methods and is included in the spectroscopic study as a pile-up component. The method is applied to data from an NE213 scintillator detector at JET and validated by comparing with results from the time-of-flight spectrometer TOFOR, which is not susceptible to pile-up distortion. Based on the results, we conclude that the suggested analysis method helps counteract the problem of pile-up effects and improves the possibilities for extracting accurate fast-ion information from the light-yield spectrum.

Novel compact hard x-ray spectrometer with MCps counting rate capabilities for runaway electron measurements on DIII-D.

A novel compact spectrometer optimized for the measurement of hard x rays generated by runaway electrons is presented. The detector is designed to be installed in the fan-shaped collimator of the gamma-ray imager diagnostic at the DIII-D tokamak. The spectrometer is based on a 1 × 1 cm2 cerium doped yttrium aluminum perovskite scintillator crystal coupled with a silicon photomultiplier. The detector dynamic energy range is in excess of 10 MeV, with an energy resolution of ∼10% at 661.7 keV. The fast detector signal (≈70 ns full width at half maximum) allows for operation at counting rates in excess of 1 MCps. The gain stability of the system can be monitored in real time using a light-emitting diode embedded in the instrument. The detector is expected to be deployed in the forthcoming DIII-D runaway electron experimental campaign.

A new tangential gamma-ray spectrometer for fast ion measurements in deuterium and deuterium-tritium plasmas of the Joint European Torus.

A new tangential gamma-ray spectrometer has been developed for fast ion measurements in deuterium and deuterium-tritium plasmas of the Joint European Torus (JET). The instrument is based on a LaBr3 crystal with a photo-multiplier tube and replaces a pre-existing bismuth germanate detector, providing enhanced energy resolution and a counting rate capability in the MHz range. The line of sight is equipped with a LiH attenuator, which reduces the background due to 14 MeV neutron interactions with the crystal by more than two orders of magnitude and enables the observation of gamma-ray emission from confined α particles in JET deuterium-tritium plasmas. Thanks to its tangential line of sight, the detector can distinguish co- and counter-passing ions. The performance of the instrument is demonstrated through the results of recent JET fast ion experiments in deuterium plasmas.

First spatially resolved measurements of the D-3He α-particle source with the upgraded JET gamma-ray camera.

The Joint European Torus (JET) gamma-ray camera has been recently upgraded with the installation of new gamma-ray detectors, based on LaBr3(Ce) scintillation crystals, which add spectroscopic capability to the existing system allowing measurements with good energy resolution (5% at 0.622 MeV), a dynamic range from hundreds of keV up to about 30 MeV, and high counting rate capabilities of MCps. First gamma-ray measurements during the C38 campaign of the JET have been successfully carried out, in particular, in D-3He plasmas from three-ion ion cyclotron resonance heating experiments, where the detection of 16.4 MeV γ-rays from D + 3He → γ + 5Li reactions with the gamma-ray camera upgrade allowed determining the spatial profile of alpha particles born in D + 3He fusion reactions.

Regulation of sodium/iodide symporter and lactoperoxidase expression in four human breast cancer cell lines.

BACKGROUND: Agents capable of increasing radioiodine concentration by stimulating the sodium/iodide symporter (NIS) expression have been extensively investigated for the treatment of certain well-differentiated breast cancers. AIM: In this study, we analyzed the regulation of the NIS and lactoperoxidase (LPO) gene expression in 4 different human breast cancer cell lines, representative of different histotypes of breast cancer. METHODS: MCF-7, T-47D, MDA-MB231, and HCC-1937 (the latter carrying the BRCA-1 mutation) were exposed to different stimulators and the levels of NIS and LPO mRNA measured by a quantitative RT-PCR. RESULTS: All-trans-Retinoic Acid (RA), Dexamethasone (DEX), Trichostatin A (TSA), and Sodium Butyrate (NaB) induced the expression of NIS mRNA in MCF-7 and T-47D cell lines, whereas HCC-1937 and MBA-MB231 were slightly responsive only to the histone-deacetylase inhibitors TSA and NaB. Minor stimulatory effects were detected on LPO mRNA in MCF-7 and T-47D treated with TSA and NaB or RA only in MCF-7, while no effect was detectable in the other two cell lines. CONCLUSIONS: These data indicate that retinoic acid, alone or in combination with DEX, as well as HDAC-inhibitors are very promising agents for a radioiodine- based therapy in a large spectrum of breast cancers, including neoplasms from both basal and ductal cells, especially for the well-differentiated estrogen-dependent tumors. Other molecules or other drug combinations should be tested to extend the same strategy to the less differentiated and more aggressive tumor cells, including those carrying the BRCA mutation.

Sensorineural hearing loss in ankylosing spondylitis treated with TNF blockers.

OBJECTIVES: Sensorineural hearing loss (SNHL) in the uncommon disease ankylosing spondylitis (AS) has been previously reported. We analysed the relationships between AS, anti-TNF drug treatment, and SNHL. METHODOLOGY: We determined pure tone thresholds in 28 consecutive patients with AS who were treated with the TNFalpha inhibitors etanercept or infliximab, or with a TNFalpha inhibitor plus methotrexate (MTX). RESULTS: SNHL was diagnosed in 16 patients (57.1%): 7/7 (100%) of those treated with anti-TNFalpha plus MTX, and 9/21 (43%) of those treated with anti-TNFalpha alone. We found a significant association between SNHL and treatment modality (p = 0.011) or treatment time in months (p = 0.020). CONCLUSIONS: The SNHL rate was significantly higher in patients treated with anti-TNFalpha plus MTX than those treated with anti-TNFalpha alone. The culpability of anti-TNF therapy was supported by the association between SNHL and treatment time, which was longer for anti-TNFalpha plus MTX than for anti-TNFalpha alone. SNHL may be due not only to AS, but also to drug-induced vasculitis of the labyrinthine artery or its cochlear branch.

Analysis of prognostic factors for the indication of central lymphadenectomy in papillary thyroid carcinomas.

BACKGROUND: In this study we examined whether it was possible following preoperative parameters statistically significant correlation with the presence of metastatic lymph nodes in the papillary thyroid carcinoma. We conducted a retrospective study in a group of patients with a preoperative diagnosis of papillary carcinoma who underwent total thyroidectomy associated with routine lymphadenectomy of the central compartment (level VI). PATIENTS AND METHODS: The study group consisted of patients whose definitive histological lymph node examination was positive for metastasis (N1), and the control group comprised patients found negative for metastasis (N0). RESULTS: Tumour diameter had a significance at 10% level [Pr(>|z|): 0.056], thus indicating that increased tumour size results in a higher probability of being in group N1. The logistic regression revealed that variables with a significance at 5% level for the presence of metastatic lymph nodes in the central compartment (N1) were: sex [Pr(>|z|): 0.019], overall patient age [Pr(>|z|): 0.012] and age >45 [Pr(>|z|): 0.022]. We performed a statistical analysis with the association of three preoperative variables (presence of ultrasound-revealed microcalcifications, presence of solid hypoechogenic nodule and type III vascularisation on echocolour-Doppler); this was found to result in a highly significant probability of entering into group N1. CONCLUSIONS: We found variables statistically significant for the presence of metastatic central compartment lymph nodes, including female sex, age >45 yrs and tumour diameter >1.5 cm. The association of papillary carcinoma with microcalcifications, solid hypoechogenic nodule structure and type III vascularisation on echocolour-Doppler also resulted in a statistically significant increase in the probability of positive level VI lymph nodes.

Optimization of MAXED input parameters with applications to the unfolding of neutron diagnostics data from the Joint European Torus.

Organic NE213 liquid scintillator neutron detectors are commonly used at accelerator facilities for neutron beam diagnostics. In recent years, they have also been installed at nuclear fusion facilities to measure the neutron energy spectra from Deuterium (D) and Deuterium-Tritium plasmas, e.g., at the ASDEX Upgrade (Garching, Germany) and at the Joint European Torus (JET, Culham, UK). The NE213 equivalent scintillating material (now BC501A) of the detector is sensitive to neutron and gamma radiation, so pulse discrimination techniques are applied in order to obtain the measured neutron pulse height spectrum (PHS). If the neutron detector is stable, controlled, and well-characterized (i.e., its response function to incoming neutrons of known energy is determined with high accuracy), it can be used as a neutron spectrometer. The measured PHS can then be analyzed using standard techniques such as unfolding to determine the incoming neutron energy spectrum. This article focuses on the unfolding of neutron data measured in D plasma experiments at JET by a compact broadband neutron spectrometer using the maximum entropy unfolding code MAXED. A general method for optimizing MAXED input parameters is described and applied to the measured PHS to diagnose the effects of the auxiliary heating of JET D plasma on the neutron energy spectra.