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We investigate the current-phase relations of Al/InAs-quantum well planar Josephson junctions fabricated using nanowire shadowing technique. Based on several experiments, we conclude that the junctions exhibit an unusually large second-order Josephson harmonic, the $\sin(2\varphi)$ term. First, superconducting quantum interference devices (dc-SQUIDs) show half-periodic oscillations, tunable by gate voltages as well as magnetic flux. Second, Josephson junction devices exhibit kinks near half-flux quantum in supercurrent diffraction patterns. Third, half-integer Shapiro steps are present in the junctions. Similar phenomena are observed in Sn/InAs quantum well devices. We perform data fitting to a numerical model with a two-component current phase relation. Analysis including a loop inductance suggests that the sign of the second harmonic term is negative. The microscopic origins of the observed effect remain to be understood. We consider alternative explanations which can account for some but not all of the evidence.

Abstract Polariton lasers are coherent light sources based on the condensation of exciton-polaritons in semiconductor microcavities, which occurs either in the kinetic or thermodynamic (Bose-Einstein) regime. Besides their fundamental interest, polariton lasers have the potential of extremely low operating thresholds. Here, we demonstrate ultra-low threshold polariton lasing at room temperature, using an all-dielectric, GaN membrane-based microcavity, with a spontaneously-formed zero-dimensional trap. The microcavity is fabricated using an innovative method, which involves photo-electrochemical etching of an InGaN sacrificial layer and allows for the incorporation of optimally-grown GaN active quantum wells inside a cavity with atomically-smooth surfaces. The resulting structure presents near-theoretical Q-factors and pronounced strong-coupling effects, with a record-high Rabi splitting of 64 meV at room-temperature. Polariton lasing is observed at threshold carrier densities 2.5 orders of magnitude lower than the exciton saturation density. Above threshold, angle-resolved emission spectra reveal an ordered pattern in k-space, attributed to polariton condensation at discrete levels of a single confinement site. This confinement mechanism along with the high material and optical quality of the microcavity, accounts for the enhanced performance of our polariton laser, and pave the way for further developments in the area of robust room temperature polaritonic devices.

Telecommunications are one of the fastest growing industries in the world and this brings serious challenges in industry technological and market development. It is very important to enable sustainable development of telecommunication networks and services to enable fast and sustainable growth at the same time. This chapter presents the model for the consolidation on telecommunication markets which derived from principles of theory of systems. Methodology has been researched through case study in a real telecommunication market environment in small country. Authors conducted time series analysis on all four telecommunication products and aggregate economic parameters on major market competitors to test rationale for consolidation action which should bring sustainable growth of the telecommunication services in country by creating stable economic environment to provide quality of service and technological development. [ABSTRACT FROM AUTHOR]

Majorana zero modes are predicted to emerge in semiconductor/superconductor interfaces, such as InAs/Al. Majorana modes could be utilized for fault tolerant topological qubits. However, their realization is hindered by materials challenges. The coupling between the superconductor and the semiconductor may be too strong for Majorana modes to emerge, due to effective doping of the semiconductor by the metallic contact. This could be mediated by adding a tunnel barrier of controlled thickness. We use density functional theory (DFT) with Hubbard U corrections, whose values are machine-learned via Bayesian optimization (BO), to assess ZnTe and CdSe as prospective tunnel barriers for the InAs/Al interface. The results of DFT+U(BO) for ZnTe are validated by comparison to angle resolved photoemission spectroscopy (ARPES). We then study bilayer interfaces of the three semiconductors with each other and with Al, as well as trilayer interfaces with a varying number of ZnTe or CdSe layers inserted between InAs and Al. We find that 16 atomic layers of either material completely insulate the InAs from metal induced gap states (MIGS). However, ZnTe and CdSe differ significantly in their band alignment, such that ZnTe forms an effective barrier for electrons, whereas CdSe forms a barrier for holes. Because of Fermi level pinning in the conduction band at the interface, only electron transport is relevant for InAs-based Majorana devices. Therefore, ZnTe is the better choice. Based on the results of our simulations, we suggest conducting experiments with ZnTe barriers in the thickness range of 6-18 atomic layers.

Background: Minimally invasive parathyroidectomy is the treatment of choice in patients with primary hyperparathyroidism (PHP), but it needs a reliable preoperative localization method to detect hyperfunctioning parathyroid tissue. Higher sensitivity and lower radiation exposure was demonstrated for [ 18 F]fluorocholine PET/CT (FCh-PET/CT) in comparison to [ 99m Tc]sestamibi (MIBI) scintigraphy. However, data of its efficiency in resource use and patient outcomes is lacking. The aim of our study was to determine the resource efficiency and patient outcomes of FCh-PET/CT in comparison to conventional MIBI scintigraphy., Patients and Methods: A group of 234 patients who underwent surgery after MIBI scintigraphy was compared to a group of 163 patients who underwent surgery after FCh-PET/CT. The whole working process from the implementation of imaging to the completion of surgical treatment was analyzed. The economic burden was expressed in the time needed for the required procedures., Results: The time needed to perform imaging was reduced by 83% after FCh-PET/CT in comparison to MIBI scintigraphy. The time needed to perform surgery was reduced by 41% when intraoperative parathyroid hormone monitoring was not used. There was no significant difference in the time of surgery between FCh-PET/CT and MIBI scintigraphy., Conclusions: FCh-PET/CT reduces the time of imaging, the time of surgery and potentially reduces the number of reoperations for persistent disease., (© 2024 Sebastijan Rep et al., published by Sciendo.)

Aim: To compare the efficacy of a postoperative continuous adductor canal block (cACB) with and without a steroid adjuvant to that of epidural analgesia (EA)., Methods: Patients who underwent primary total TKA at a single institution between July 2011-November 2017 were included for retrospective analysis. TKA patients were stratified into one of the three analgesia approaches: EA, cACB without steroid adjuvant, and cACB with steroid adjuvant. Hospital length of stay (LOS), discharge disposition, incidence of postoperative adverse events, and total milligram morphine equivalents (MME) requirements were compared between strata. Logistic regressions were performed to assess the independent effect of analgesia approach on prolonged LOS greater than 3 days (pLOS), non-home discharge, and total and daily MME requirements (tMME and dMME) following TKA., Results: Of the 4345 patients undergoing TKA, 1556 (35.83%) received EA, 2087 (48.03%) received cACB without steroids, and 702 (16.13%) cACB with steroids. cACB patients experienced lower rates of pLOS, higher rates of discharge to home than EA patients, and lower tMME and dMME. On multivariable analysis, cACB groups were at a lower odds of experiencing a pLOS compared to EA patients without steroids (OR = 0.64; 95% CI 0.49-0.84; with steroids: OR = 0.54; 95% CI 0.38-0.76). cACB groups had lower odds of a non-home discharge when compared to EA patients (without steroids OR = 0.42; 95% CI 0.36-0.48; with steroids: OR 0.22; 95% CI 0.18-0.27). On multivariable analysis, cACB groups required less tMME compared to the EA group (without steroids β=-290 mmE; 95% CI: -313 to -268 mmE; with steroids: β=-261 mmE; 95% CI: -289 to -233 mmE) as well as lower dMME (without steroids: β=-66 mmE/day; 95% CI -72 to -60 mmE/day; with steroids: β=-48 mmE/day; 95% CI -55 to -40 mmE/day)., Conclusion: cACB was associated with greater discharge to home rates, lower rates of pLOS, and lower tMME and dMME consumption., Level of Evidence: Level III., Competing Interests: The following disclosures have been collected and reported per International Committee of Medical Journal Editors (ICMJE) reporting standards. Dr. Isaac G. Freedman has nothing to disclose. Dr. Michael R. Mercier has nothing to disclose. Dr. Anoop R. Galivanche has nothing to disclose. Dr. Mani Ratnesh S. Sandhu has nothing to disclose. Mr. Mark Hocevar has nothing to disclose. Dr. Harold G. Moore has nothing to disclose. Dr. Jonathan N. Grauer reports personal fees from TIDI products, personal fees from the North American Spine Society, is the Editor-in-Chief of the North American Spine Society Journal outside the submitted work. Dr. Jinlei Li has nothing to disclose. Dr. Lee E. Rubin reports personal fees from DePuy Synthes, personal fees from ConvaTec, personal fees from Innovative Medical Products, personal fees from Thompson Surgical Instruments, personal fees from SLACK, Inc. Publishers, personal fees from Johns Hopkins University Press, other from 3D Surgical, Inc., outside the submitted work. None pertaining to the subject or content of this work., (© 2024 Freedman et al.)

Study objective The purpose of this study is to investigate the analgesic efficacy of ultrasound-guided fascial plane blocks (FPBs) versus local infiltration in patients undergoing laparoscopic non-donor nephrectomy. This study specifically compares the efficacy of FPBs with liposomal bupivacaine (LB) versus FPBs with dexamethasone sodium phosphate (DXP) and methylprednisolone acetate (MPA) versus surgical site local anesthetic infiltration without FPBs.  Design This is a retrospective cohort study conducted over a five-year period (January 2018-December 2022). Setting The study was conducted in a tertiary care, academic, multi-hospital healthcare system.  Participants Patients who underwent elective radical or partial laparoscopic non-donor nephrectomy were included in the study. Intervention Patients either received preoperative FPBs without intraoperative surgical site local anesthetic infiltration or received surgical site local anesthetic infiltration without FPBs (n = 141) at participating hospitals. Measurements The primary endpoint of this study was postoperative opioid use, measured as oral milligram morphine equivalents (MME). Secondary endpoints included postoperative pain scores, length of hospital stays, and significant adverse events within 30 days. The impact of medications utilized in FPBs was determined by univariate and multivariable analyses with covariates balancing propensity score weighting. Main results Patients undergoing non-donor laparoscopic radical or partial nephrectomy who received FPBs with bupivacaine or ropivacaine plus glucocorticoids DXP and MPA were more likely to be opioid-free 24-48 hours postoperatively compared to those who received FPBs with LB or surgical site local anesthetic infiltration without FPBs (40.5% vs. 30% vs. 13.9%, respectively; p = 0.017). Patients who received FPBs with glucocorticoids also reported the lowest pain scores at rest and with activity 0-12 hours postoperatively as compared to patients who received LB or local infiltration (p = 0.006 and p = 0.014, respectively). Additionally, patients who received FPBs with glucocorticoids received over 30% fewer opioids during the first 48 hours postoperatively compared to patients who received surgical site local anesthetic infiltration alone (30 MME vs. 44 MME, respectively). However, there was no significant difference in total opioid use during the first 48 hours postoperatively between patients who received FPBs with bupivacaine plus glucocorticoids and those who received FPBs with bupivacaine plus LB (mean ratio: 0.91, (95% CI: 0.05 ~ 15.97); p = 0.948). There was also no difference in the length of hospital stays or rate of adverse events between the groups. Conclusion Perioperative FPBs for non-donor laparoscopic nephrectomy using glucocorticoids as an adjuvant to long-acting local anesthetics may decrease postoperative opioid use and reduce pain scores as compared to FPBs with LB or surgical site local anesthetic infiltration. Bupivacaine or ropivacaine combined with DXP and MPA is a safe and effective alternative to LB for FPBs in laparoscopic nephrectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Yale School of Medicine Institutional Review Board (IRB) issued approval (2000029282). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sobhani et al.)

Background: The most common route of opioid delivery is nurse-administered pills. However, there are numerous challenges such as nursing burden, opioid diversion, medication delay, and patient dissatisfaction. In this study, we conducted two surveys, first to assess patients' and nurses' opinions on the current administration of opioids in pill form, followed by their attitudes towards an innovative concept of oral medication delivery based on a medical device currently undergoing research and development within the University, patient-controlled dispenser and deactivator (PCDD) that allows patients to self-administer liquid oral opioids on demand based on physician prescription., Methods: Questionnaires were developed, verified and deployed to assess nurse and post-surgical patient opinions on the current administration of opioids in pill form, as well as the proposed new concept of patient -controlled administration of oral liquid medication via an illustration of PCDD, from September 2022 through July 2023 at a major academic tertiary care center. Quantitative and qualitative data were collected from postoperative patients and nurses from surgical specialties including General Surgery, Surgical Oncology, Trauma Surgery, Orthopedics, and Neurosurgery., Results: Forty-three patients and 53 nurses were interviewed. Seventy percent of patients frequently called nurses for pain medication post-surgery 1-4 times daily, and 32% of patients were told each day by nurses that they could not receive medication because they were not due yet. Medication delay caused 24% of patients to worry about nursing availability for medication delivery. Likewise, nurses reported that half of patients receive delayed medication (22 minutes median delay time) and half of nursing time was spent administering pain medication. Nurses expressed moderate satisfaction with their current delivery of medication (median satisfaction score 6.5 out of 10). When being introduced to the concept of PCDD via a product illustration, 15% of patients said that they prefer liquid medication and 51% said they prefer PCDD or were interested in trying it., Conclusion: Nurse-administered pills are a common but suboptimal method for postoperative pain management. Based on patient and nurse feedback, patient controlled self-administered liquid oral opioid delivery is conceptually innovative, practically viable and potentially a preferred alternative for timely and less nurse-exhaustive pain management., Competing Interests: Daniel Wiznia, Jinlei Li, and Claudia See report a patent “Patient-controlled liquid oral medicine dispenser and deactivation system (US11857504B1)” issued. All authors report no other conflicts of interest relevant to this manuscript., (© 2024 Mirza et al.)

Background: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique., Methods: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations., Results: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training., Conclusion: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP., Competing Interests: Declaration of competing interest Angela Märten works as a consultant for Belpharma SA., (© 2024 Published by Elsevier Ltd.)

Metal deposition with cryogenic cooling is a common technique in the condensed matter community for producing ultra-thin epitaxial superconducting layers on semiconductors. However, a significant challenge arises when these films return to room temperature, as they tend to undergo dewetting. This issue can be mitigated by capping the films with an amorphous layer. In this study, we investigate the influence of different in situ fabricated caps on the structural characteristics of Sn thin films deposited at 80 K on InSb substrates. Regardless of the type of capping, we consistently observe that the films remain smooth upon returning to room temperature and exhibit epitaxy on InSb in the cubic Sn ( α -Sn) phase. Notably, we identify a correlation between alumina capping using an electron beam evaporator and an increased presence of tetragonal Sn ( β -Sn) grains. This suggests that heating from the alumina source may induce a partial phase transition in the Sn layer. The existence of the β -Sn phase induces superconducting behavior of the films by percolation effect. This study highlights the potential for tailoring the structural properties of cryogenic Sn thin films through in situ capping. This development opens avenues for precise control in the production of superconducting Sn films, facilitating their integration into quantum computing platforms., (© 2023 IOP Publishing Ltd.)

Abstract: The purpose of this report was to estimate the additional annual cost to the U.S. healthcare system attributable to preventable medication errors (MEs) in the operating room. The ME types were iteratively grouped by their associated harm (or potential harm) into 13 categories, and we determined the incidence of operations involving each ME category (number of operations involving each category/total number of operations): (1) delayed or missed required perioperative antibiotic (1.4% of operations); (2) prolonged hemodynamic swings (7.6% of operations); (3) untreated postoperative pain >4/10 (18.9% of operations); (4) residual neuromuscular blockade (2.9% of operations); (5) oxygen saturation <90% due to ME (1.8% of operations); (6) delayed emergence (1.1% of operations); (7) untreated new onset intraoperative cardiac arrhythmia (0.72% of operations); (8) medication documentation errors (7.6% of operations); (9) syringe swaps (5.8% of operations); (10) presumed hypotension with inability to obtain a blood pressure reading (2.2% of operations); (11) potential for bacterial contamination due to expired medication syringes (8.3% of operations); (12) untreated bradycardia <40 beats/min (1.1% of operations); and (13) other (13.0% of operations). Through a PubMed search, we determined the likelihood that the ME category would result in downstream patient harm such as surgical site infection or acute kidney injury, and the additional fully allocated cost of care (in 2021 U.S. dollars) for each potential downstream patient harm event. We then estimated the cost of the MEs across the U.S. healthcare system by scaling the number of MEs to the total number of annual operations in the United States (N = 19,800,000). The total estimated additional fully allocated annual cost of care due to perioperative MEs was $5.33 billion U.S. dollars., Competing Interests: M.E.L. reports stock options from Guided Clinical Solutions (Boston, Massachusetts). K.C.N. reports author royalties from UpToDate, Inc (Waltham, Massachusetts), equity from Guided Clinical Solutions (Boston, Massachusetts), and consulting fees from NORC at the University of Chicago. The remaining authors disclose no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Majorana zero modes, with prospective applications in topological quantum computing, are expected to arise in superconductor/semiconductor interfaces, such as β-Sn and InSb. However, proximity to the superconductor may also adversely affect the semiconductor's local properties. A tunnel barrier inserted at the interface could resolve this issue. We assess the wide band gap semiconductor, CdTe, as a candidate material to mediate the coupling at the lattice-matched interface between α-Sn and InSb. To this end, we use density functional theory (DFT) with Hubbard U corrections, whose values are machine-learned via Bayesian optimization (BO) [ npj Computational Materials 2020, 6, 180]. The results of DFT+U(BO) are validated against angle resolved photoemission spectroscopy (ARPES) experiments for α-Sn and CdTe. For CdTe, the z -unfolding method [ Advanced Quantum Technologies 2022, 5, 2100033] is used to resolve the contributions of different k z values to the ARPES. We then study the band offsets and the penetration depth of metal-induced gap states (MIGS) in bilayer interfaces of InSb/α-Sn, InSb/CdTe, and CdTe/α-Sn, as well as in trilayer interfaces of InSb/CdTe/α-Sn with increasing thickness of CdTe. We find that 16 atomic layers (3.5 nm) of CdTe can serve as a tunnel barrier, effectively shielding the InSb from MIGS from the α-Sn. This may guide the choice of dimensions of the CdTe barrier to mediate the coupling in semiconductor-superconductor devices in future Majorana zero modes experiments.

Background: In the setting of primary hyperparathyroidism (PHPT), [ 18 F]fluorocholine PET/CT (FCH-PET) has excellent diagnostic performance, with experienced practitioners achieving 97.7% accuracy in localising hyperfunctioning parathyroid tissue (HPTT). Due to the relative triviality of the task for human readers, we explored the performance of deep learning (DL) methods for HPTT detection and localisation on FCH-PET images in the setting of PHPT., Patients and Methods: We used a dataset of 93 subjects with PHPT imaged using FCH-PET, of which 74 subjects had visible HPTT while 19 controls had no visible HPTT on FCH-PET. A conventional Resnet10 as well as a novel mPETResnet10 DL model were trained and tested to detect (present, not present) and localise (upper left, lower left, upper right or lower right) HPTT. Our mPETResnet10 architecture also contained a region-of-interest masking algorithm that we evaluated qualitatively in order to try to explain the model's decision process., Results: The models detected the presence of HPTT with an accuracy of 83% and determined the quadrant of HPTT with an accuracy of 74%. The DL methods performed statistically worse (p < 0.001) in both tasks compared to human readers, who localise HPTT with the accuracy of 97.7%. The produced region-of-interest mask, while not showing a consistent added value in the qualitative evaluation of model's decision process, had correctly identified the foreground PET signal., Conclusions: Our experiment is the first reported use of DL analysis of FCH-PET in PHPT. We have shown that it is possible to utilize DL methods with FCH-PET to detect and localize HPTT. Given our small dataset of 93 subjects, results are nevertheless promising for further research., (© 2022 Leon Jarabek, Jan Jamsek, Anka Cuderman, Sebastijan Rep, Marko Hocevar, Tomaz Kocjan, Mojca Jensterle, Ziga Spiclin, Ziga Macek Lezaic, Filip Cvetko, Luka Lezaic, published by Sciendo.)

Purpose: Lateral neck nodal metastases are common in patients with differentiated thyroid cancer (DTC) and usually have an indolent nature. They may be detected via neck palpation or preoperative ultrasound (US) of the neck. We hypothesized that preoperative neck metastases detected with US did not affect regional recurrence or long-term survival., Methods: A retrospective analysis of patients' records treated for DTC at our institution between January 2006 and December 2016 was performed. Information about preoperative US of the neck, treatment, demographics, staging, and histopathology was obtained. The endpoints for the study were nodal recurrence and survival. Differences in survival were analyzed between three groups of patients divided by presence or lack of preoperative US and/or palpable cervical lymph nodes (PLN). Furthermore, the prognostic value of multiple variables was tested by univariate and multivariate analysis., Results: There were 1108 patients with DTC, 221 males and 887 females. The median age was 48.3 years (range 3 to 86), the median time of observation was 68 months (range 0 to 142). Eight hundred sixty-two patients without PLN or preoperative US represented group 1, 112 patients with PLN were in group 2, and 134 patients without PLN and with preoperative US were in group 3. Only five patients had a regional recurrence, one died due to distant metastases. There was no statistically significant difference in survival between the groups (p = 0.841) and neck US was not significantly associated with overall survival neither in univariate nor in multivariate analysis., Conclusion: In patients with DTC, the benefits of preoperative US of cervical lymph nodes are probably limited and "less is more" approach is advised., (© 2021. The Author(s).)

Introduction: Hypercalcaemia is most commonly a sign of primary hyperparathyroidism but can also be a sign of an active granulomatous disease. Standard treatment for primary hyperparathyroidism caused by a solitary parathyroid gland adenoma identified by localisation studies is minimally invasive focused parathyroidectomy. If unsuccessful, bilateral neck exploration is recommended., Case Presentation: We report the case of hypercalcaemia and ostheoporosis in a 63-year -old woman with a history of sarcoidosis and suspected primary hyperparathyroidism. Localisation studies for parathyroid adenoma were inconclusive due to active cervical and mediastinal granulomatous lymph nodes. Sarcoidosis was treated with corticosteroids but hypercalcaemia persisted. Focused parathyroidectomy was attempted with intraoperative parathyroid hormone measurement but an increase in parathyroid hormone levels was observed. However, with high clinical probability of a successfully removed adenoma and frozen section evaluation, we decided not to proceed with bilateral neck exploration. Serum parathyroid hormone and calcium levels dropped accordingly the following day., Clinical Discussion: We explored all possible underlying mechanisms for persistent elevated parathyroid hormone level described in literature., Conclusion: We conclude that Wisconsin Criteria with intraoperative parathyroid hormone measured 20 minutes after adenoma removal should be applied in such cases., Competing Interests: None declared., (© 2021 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Improving materials used to make qubits is crucial to further progress in quantum information processing. Of particular interest are semiconductor-superconductor heterostructures that are expected to form the basis of topological quantum computing. We grew semiconductor indium antimonide nanowires that were coated with shells of tin of uniform thickness. No interdiffusion was observed at the interface between Sn and InSb. Tunnel junctions were prepared by in situ shadowing. Despite the lack of lattice matching between Sn and InSb, a 15-nanometer-thick shell of tin was found to induce a hard superconducting gap, with superconductivity persisting in magnetic field up to 4 teslas. A small island of Sn-InSb exhibits the two-electron charging effect. These findings suggest a less restrictive approach to fabricating superconducting and topological quantum circuits., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: Medullary thyroid cancer (MTC) is a challenging neuroendocrine malignancy where the role of nuclear medicine imaging is currently limited. This paper investigates the potential diagnostic value of [ 18 F]Fluorocholine PET/CT in primary MTC., Methods: We prospectively enrolled 25 patients (10 male, 15 female) with suspicion for primary MTC based on fine-needle aspiration biopsy (FNAB). All patients had a baseline three phase [ 18 F]Fluorocholine PET/CT (2.5 MBq/kg): two regional head and neck and upper mediastinum studies at 5 min (first phase) and 120 min (third phase) and a whole-body PET/CT (from the skull vertex to mid-thighs) at 60 min (second phase). Any non-physiological radiotracer uptake was regarded as MTC positive. All patients referred to surgery had a preoperative neck-US. True lesion status was assessed using either histopathology, FNAB results or follow-up imaging and laboratory (calcitonin, CEA) results. Results with p < 0.05 were considered statistically significant., Results: Nineteen of 25 patients (76%) were surgically treated and histopathology reports were obtained. Patient-based sensitivity and positive predictive value for detection of any MTC lesion using [ 18 F]Fluorocholine PET/CT were both 100%. Neck-US was more specific (100% vs 70%; p = 0.002) and had a higher positive predictive value than [ 18 F]Fluorocholine PET/CT (100% vs 55%; p = 0.018) for N1a and N1b staging. [ 18 F]Fluorocholine PET/CT had a higher sensitivity (100% vs 50%; p = 0.025) and higher negative predictive value (100% vs 81%; p = 0.026) than neck-US for N1b staging. The optimal SUV max cut-off to differentiate malignant from benign neck lesions at 60 and 120 min was 2.56. Patients with M1 stage on PET/CT had higher calcitonin (median of 5,372 vs 496.6 pg/ml; p = 0.005) and CEA concentrations (median of 95.8 vs 18.65 µg/l; p = 0.034) compared to patients with M0 disease., Conclusion: [ 18 F]Fluorocholine PET/CT appears to be a promising radiotracer for primary staging of MTC by increasing diagnostic accuracy for N staging and detecting possible distant metastatic sites at initial presentation of disease.

Background: Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients' treatment from Slovenian national CM register to leading international clinical guidelines., Patients and Methods: Since 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests., Results: Positive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs . 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs . 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs . 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs . 47%; p = 0.280)., Conclusions: Stage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III., (© 2021 Barbara Peric, Sara Milicevic, Andraz Perhavec, Marko Hocevar, Janez Zgajnar, published by Sciendo.)

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18 F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18 F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99m Tc-sestamibi SPECT/CT, 99m Tc-sestamibi/pertechnetate subtraction imaging, and 99m Tc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18 F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%-56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%-34% (44% combined). Conclusion: 18 F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background Primary hyperparathyroidism is the third most common endocrine disorder for which surgical procedure called parathyroidectomy is the most effective treatment. Since the early 20th century, parathyroid surgery has improved extensively. With the advances in preoperative imaging and with understanding the causes of disease, new and minimally invasive surgical approaches overrode the standard bilateral exploratory operations. Directed parathyroidectomy is currently the standard technique for treatment of primary hyperparathyroidism worldwide. Conclusions Surgery is the only definitive treatment of primary hyperparathyroidism. The most appropriate type of surgical procedure depends on the number and localization of the hyperactive parathyroid glands, availability of modern imaging techniques, limitation of each type of procedure and expertise.

We perform tunneling measurements on indium antimonide nanowire-superconductor hybrid devices fabricated for the studies of Majorana bound states. At finite magnetic field, resonances that strongly resemble Majorana bound states, including zero-bias pinning, become common to the point of ubiquity. Since Majorana bound states are predicted in only a limited parameter range in nanowire devices, we seek an alternative explanation for the observed zero-bias peaks. With the help of a self-consistent Poission-Schrödinger multiband model developed in parallel, we identify several families of trivial subgap states that overlap and interact, giving rise to a crowded spectrum near zero energy and zero-bias conductance peaks in experiments. These findings advance the search for Majorana bound states through improved understanding of broader phenomena found in superconductor-semiconductor systems.

We present a comprehensive study of the performance of GaN single-nanowire photodetectors containing an axial p-n junction. The electrical contact to the p region of the diode is made by including a p + /n + tunnel junction as cap structure, which allows the use of the same metal scheme to contact both ends of the nanowire. Single-nanowire devices present the rectifying current-voltage characteristic of a p-n diode but their photovoltaic response to ultraviolet radiation scales sublinearly with the incident optical power. This behavior is attributed to the dominant role of surface states. Nevertheless, when the junction is reverse biased, the role of the surface becomes negligible in comparison to the drift of photogenerated carriers in the depletion region. Therefore, the responsivity increases by about 3 orders of magnitude and the photocurrent scales linearly with the excitation. These reverse-biased nanowires display decay times in the range of ∼10 μs, limited by the resistor-capacitor time constant of the setup. Their ultraviolet/visible contrast of several orders of magnitude is suitable for applications requiring high spectral selectivity. When the junction is forward biased, the device behaves as a GaN photoconductor with an increase of the responsivity at the price of a degradation of the time response. The presence of leakage current in some of the wires can be modeled as a shunt resistance which reacts to the radiation as a photoconductor and can dominate the response of the wire even under reverse bias.

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved., Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics., Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance., Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling., (Copyright © 2019 American Academy of Dermatology, Inc. All rights reserved.)

Paclitaxel induces microglial activation and production of proinflammatory mediators in the dorsal horn, which contribute to the development and maintenance of central sensitization and pain behavior. MDA7, 1-([3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl]carbonyl) piperidine, is a novel highly selective cannabinoid type 2 (CB2) agonist. We tested the hypothesis that activation of CB2 receptor by MDA7 modulates microglial dysregulation, suppresses the overexpression of brain-derived neurotrophic factor (BDNF) in microglia in the dorsal horn, and attenuates the central sensitization and pain behavior induced by paclitaxel. For 4 consecutice days, groups of rats randomly received saline or 1.0 mg/kg of paclitaxel daily intraperitoneally for a total cumulative dose of 4 mg/kg. MDA7 15 mg/kg intraperitoneally or vehicle were administered 15 min before administering paclitaxel for 4 days and then continued for another 10 days. Behavioral and molecular studies were performed. Paclitaxel induced the expression of CB2 receptors and production of interleukin (IL)-6 in microglia in the dorsal horn. MDA7 attenuated the expression of IL-6 and promoted the expression of IL-10. Paclitaxel induced epigenetic upregulation of IRF8 and P2X purinoceptor 4 (P2X4) in microglia and subsequently increased the expression of alpha isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIα), transcriptional factors p-CREB and ΔFosB, leading to the overproduction of BDNF in microglia. Paclitaxel also upregulated the expression of glutamate receptor subunits GluR1 and NR2B, decreased the expression of K + -Cl - cotransporter, and induced mechanical allodynia in rats. All of the aforementioned molecular changes were attenuated by MDA7. Our data show that MDA7 attenuated paclitaxel-induced molecular and behavioral changes in rats. Perspective: This study provides evidence that paclitaxel induced microglia dysregulation and epigenetically upregulated the microglial expression of BDNF, which led to sensitization of dorsal horn neurons and mechanical allodynia in rats. The CB2 agonist MDA7 alleviated these pathological processes. MDA7 represents an innovative therapeutic approach for treatment of chemotherapy-induced neuropathy., (Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: High-grade serous ovarian cancer is a detrimental disease. Treatment options in patients with a recurrent disease are dependent on BRCA1/2 mutation status since only patients with known BRCA mutation are eligible for treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). The aim of this study was to compare concordance of BRCA mutation analyses from cytological samples (CS) with BRCA mutation analyses from histological formalin fixed paraffin embedded (FFPE) samples., Methods: Mutation analysis of BRCA1 and BRCA2 genes was performed in 44 women diagnosed with primary or recurrent high-grade ovarian cancer from three different samples: blood, cytological sample (ascites, pleural effusion and enlarged lymph nodes) and tumor tissue. Results from all three samples were compared., Results: Among 44 patients, there were 15 germline mutations and two somatic mutations. A 100% concordance was found between cytological and histologic samples., Conclusion: There is a 100% concordance in BRCA mutation testing between cytological and histologic samples. BRCA mutation testing from CS could replace testing from FFPE tissue in clinical decision making in ovarian cancer patients., Trial Registration: The study was retrospectively registered at ISRCTN registry on 24/11/2015 - ISRCTN42408038 .

Detecting nanomechanical motion has become an important challenge in science and technology. Recently, electromechanical coupling to focused electron beams has emerged as a promising method adapted to ultralow scale systems. However the fundamental measurement processes associated with such complex interaction remain to be explored. Here we report a highly sensitive detection of the Brownian motion of μm-long semiconductor nanowires (InAs). The measurement imprecision is found to be set by the shot noise of the secondary electrons generated along the electromechanical interaction. By carefully analyzing the nanoelectromechanical dynamics, we demonstrate the existence of a radial backaction process that we identify as originating from the momentum exchange between the electron beam and the nanomechanical device, which is also known as radiation pressure.

Background: A significant disparity regarding survival outcome for melanoma among European regions is well recognized and access to high quality care for European melanoma patients needs to be improved. There is an unmet need for the implementation of minimal standard of care within defined clinical pathways and Quality Assurance (QA) indicators., Objective: The EU-MELACARE study aims to identify shared variables for cutaneous melanoma cases recorded in melanoma registries across Europe., Material and Methods: Opinion leaders involved in melanoma data registration and care quality analysis in 34 European countries were invited to respond to an expert survey covering questions regarding the melanoma registration practice in their countries and the characteristics, coverage and variables collected by the relevant melanoma registries., Results: Data regarding 13 melanoma registries from 11 European countries contributed to the study. The majority (61,5%) were population based registries and more than half (62%) had national coverage. The included registries collected a median of 38 variables (Interquartile Range, IRQ 21-76). We identified 24 shared variables available in >70% of registries., Conclusions: This study provides valuable specific information on information recorded for melanoma cases are registered within Europe. A core of shared variables has been identified, which will constitute the basis for a standardized set of QA indicators for assessing and monitoring melanoma care across European countries., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

We study transport mediated by Andreev bound states formed in InSb nanowire quantum dots. Two kinds of superconducting source and drain contacts are used: epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple times at increasing source-drain bias voltages. In both devices, a mirage of a crowded spectrum is created. To describe the observations a model is developed that combines the effects of a soft induced gap and of additional Andreev bound states both in the quantum dot and in the finite regions of the nanowire adjacent to the quantum dot. Understanding of Andreev spectroscopy is important for the correct interpretation of Majorana experiments done on the same structures.

Background: Parathyroid subtraction scintigraphy (PSS) is the most commonly used imaging method for localisation of hyperfunctioning parathyroid glands (HPGs) in primary hyperparathyroidism (PHP), a common endocrine disorder. Hybrid (SPECT/CT) imaging with 99m Tc-sestaMIBI (MIBI) at an early and delayed phase (dual-phase imaging) may be the most accurate conventional imaging approach, but includes additional radiation exposure due to added CT imaging. Recently, 18 F-choline (FCH) PET/CT was introduced for HPG imaging, which can also be performed using the dual-phase approach. To date, no studies have compared organ doses and the effective dose (ED) from conventional subtraction scintigraphy, dual-phase MIBI SPECT/CT, and FCH PET/CT in the localisation of HPGs., Aim: In addition to the comparison of the diagnostic performance of FCH PET/CT and conventional scintigraphic imaging methods, the aim of the study was to measure the organ doses and the ED for conventional subtraction parathyroid imaging protocols, using dual-phase MIBI SPECT/CT as a potential conventional imaging method of choice and FCH dual-phase PET/CT as a potential future imaging method of choice for the localisation of HPGs. Materials, methods. Thirty-six patients referred for parathyroid imaging with a clinical indication of PHP underwent preoperative PSS and dual-phase SPECT/CT imaging with the addition of FCH PET/CT. The diagnostic performance of the imaging modalities was assessed by using histology results as a gold standard. Radiation exposure was calculated for the administered activities of radiopharmaceuticals using ICRP80 weighting factors and for CT exposure at hybrid imaging using dose-length products and the ImPACT CT Patient Dosimetry Calculator., Results: The diagnostic performance of FCH PET/CT was significantly better than that of conventional imaging modalities (sensitivity of 97% vs 64% and 46% for MIBI SPECT/CT and PSS, respectively, with comparable specificity of over 95% for all modalities). The highest radiation exposure was caused by conventional PSS (7.4 mSv), followed by dual-phase MIBI SPECT/CT (6.8 mSv). The radiation exposure was the lowest for dual-phase FCH PET/CT imaging (2.8 mSv). The added CT imaging for both hybrid approaches did not cause significant additional radiation exposure (1.4 mSv for MIBI SPECT/CT, additional 26.4% to overall exposure; 0.8 mSv for FCH PET/CT, additional 42.4% to overall exposure)., Conclusion: In comparison to conventional scintigraphic imaging of HPGs, emerging hybrid (SPECT/CT, PET/CT) imaging techniques combine superior diagnostic performance with lower radiation exposure to patients.

Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18-2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92-1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94-1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75-4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Chains of quantum dots coupled to superconductors are promising for the realization of the Kitaev model of a topological superconductor. While individual superconducting quantum dots have been explored, control of longer chains requires understanding of interdot coupling. Here, double quantum dots are defined by gate voltages in indium antimonide nanowires. High transparency superconducting niobium titanium nitride contacts are made to each of the dots in order to induce superconductivity, as well as probe electron transport. Andreev bound states induced on each of dots hybridize to define Andreev molecular states. The evolution of these states is studied as a function of charge parity on the dots, and in magnetic field. The experiments are found in agreement with a numerical model.Quantum dots in a nanowire are one possible approach to creating a solid-state quantum simulator. Here, the authors demonstrate the coupling of electronic states in a double quantum dot to form Andreev molecule states; a potential building block for longer chains suitable for quantum simulation.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuroinflammation, extensive deposits of amyloid-β aggregates, and loss of memory and cognitive abilities. The brains of patients with AD show increased expression of cannabinoid receptor type 2 (CB 2 ) receptors and glial markers. CB 2 receptors act as a negative feedback regulator; when activated by a CB 2 agonist, they can help limit the extent of the neuroinflammatory response and the subsequent development of neuronal damage in the central nervous system. In a double transgenic APP/PS1 mice model of AD, we evaluated the effect of MDA7, a CB2 agonist, on several neuropathological conditions of AD including amyloid deposition, inflammatory reaction, Sox2 (sex-determining region Y-box 2) expression, and spatial memory. Activation of microglia CB 2 receptors by MDA7 suppressed neuroinflammation, demonstrated by decreased immunosignal of Iba1 in the hippocampal CA1 and dentate gyrus (DG) areas, promoted clearance of amyloid plaques in the DG area, restored Sox2 expression, and promoted recovery of the neuronal synaptic plasticity in hippocampal CA1. In addition, treatment with MDA7 improved the behavioral performance in the Morris water maze in APP/PS1mice. Collectively, these findings suggest that MDA7 has a potential therapeutic effect in the setting of AD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Topological superconductivity is an exotic state of matter characterized by spinless p-wave Cooper pairing of electrons and by Majorana zero modes at the edges. The first signature of topological superconductivity is a robust zero-bias peak in tunneling conductance. We perform tunneling experiments on semiconductor nanowires (InSb) coupled to superconductors (NbTiN) and establish the zero-bias peak phase in the space of gate voltage and external magnetic field. Our findings are consistent with calculations for a finite-length topological nanowire and provide means for Majorana manipulation as required for braiding and topological quantum bits.

We report on the growth of axial InAs-on-GaAs nanowire heterostructures on silicon by molecular beam epitaxy using 20 nm diameter Au catalysts. First, the growth parameters of the GaAs nanowire segment were optimized to achieve a pure wurtzite crystal structure. Then, we developed a two-step growth procedure to enhance the yield of vertical InAs-on-GaAs nanowires. We achieved 90% of straight InAs-on-GaAs nanowires by further optimizing the growth parameters. We investigated the composition change at the interface by energy dispersive x-ray spectroscopy and the nanowire crystal structure by transmission electron microscopy. The composition of the nominal InAs segment is found to be In x Ga 1-x As with x = 0.85 and corresponds to 6% of lattice mismatch with GaAs. Strain mapping performed by the geometrical phase analysis of high-resolution images revealed a dislocation-free GaAs/In 0.85 Ga 0.15 As interface. In conclusion, we successfully fabricated highly mismatched heterostructures, confirming the prediction that axial GaAs/In 0.85 Ga 0.15 As interfaces are pseudomorphic in nanowires with a diameter smaller than 40 nm.

Background: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years., Patients and Methods: All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities., Results: Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected., Conclusions: The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered., Competing Interests: Disclosure: No potential conflicts of interest were disclosed.

A focused surgical approach based on pre-operative localization replaced the classical four-gland exploration in patients with primary hyperparathyroidism (PHP). Sestamibi scanning and ultrasound are most often used localization modalities with reported sensitivity of 54-100% for identification of single gland disease. The aim of this study was to analyze the results of pre-operative localization with 18 F-Fluorocholine PET/CT (FCh-PET) in patients with PHP. A retrospective review of 151 patients with PHP who underwent surgery after pre-operative localization with FCh-PET was performed. Only a focused parathyroidectomy without ioPTH testing had been done in patients with single adenoma on FCh-PET. Primary outcome was operative failure, defined as persistent PHP. According to pre-operative FCh-PET 126 (83,4%) patients had single adenoma, 22 (14,5%) multiglandular disease and the test was negative in only two patients. Intraoperative failure experienced 4/126 patients (3,3%) with single adenoma. Removed parathyroid glands were normal in three and hyperplastic in one patient with intraoperative failure. A limited bilateral neck exploration with ioPTH testing was used in 14/22 patients with double adenoma and a classical four-gland exploration without ioPTH testing was used in 8/22 patients with more than two pathological glands according to pre-operative FCh-PET. Intraoperative failure experienced 2/22 patients (9,1%). In two patients with negative FCh-PET a classical four-gland exploration without ioPTH testing was used and one experienced intraoperative failure. A preoperative localization with FCh-PET is a reliable test in patients with PHP. Patients with a single adenoma on FCh-PET can safely undergo a focused parathyroidectomy without ioPTH testing., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Competing Interests: The authors state no conflict of interest.

Background: Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [(18)F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism., Patients and Methods: 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated., Results: Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05)., Conclusions: According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.

Purpose: Primary hyperparathyroidism is a common endocrine disorder which is diagnosed biochemically and for which therapy is surgical. A prerequisite for minimally invasive surgery, which minimizes morbidity and cost, is accurate localization of the involved gland(s). The aim of this study was to evaluate the usefulness of (18)F-fluorocholine PET/CT for preoperative localization of hyperfunctioning parathyroid tissue., Methods: (18)F-Fluorocholine PET/CT and conventional parathyroid scintigraphic imaging consisting of (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI dual-phase imaging and (99m)Tc-sestaMIBI/pertechnetate subtraction imaging were performed in 24 patients. The diagnostic performance of the imaging methods was compared against histology as the gold standard and postoperative serum Ca(2+) and iPTH values., Results: The sensitivity and specificity of (18)F-fluorocholine PET/CT were 92% and 100%, respectively, in contrast to 49% and 100%, 46% and 100%, and 44% and 100% for (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI/pertechnetate subtraction imaging and (99m)Tc-sestaMIBI dual-phase imaging, respectively. Combined conventional scintigraphic imaging had a sensitivity and specificity of 64% and 100%, respectively. The performance of (18)F-fluorocholine PET/CT was superior particularly in patients with multiple lesions or hyperplasia., Conclusion: (18)F-Fluorocholine PET/CT appears to be a promising, effective imaging method for localization of hyperfunctioning parathyroid tissue.

Unlabelled: The aim of this study was to evaluate the effect of a residual melanoma after an excisional biopsy on prognosis of patients with cutaneous melanoma., Patients and Methods: Between 2000 and 2007 sentinel lymph node biopsy with wide reexcision of a primary melanoma site was successfully performed in 692 patients (315 male and 377 female; mean age 55.7 years) at the Institute of Oncology Ljubljana, Slovenia. Clinicopathological data of all patients were extracted from a prospective institutional melanoma database and the frequency of local recurrences and survival were compared between patients with residual melanoma and those without it. For a statistical analysis univariate and multivariate analyses were used., Results: Only 25 (3.6%) patients had a residual melanoma. There was no difference in mean tumor thickness (3.9 and 2.8 mm) and ulceration (40% and 34%) of the primary melanoma between patients with and without residual melanoma. However, a number of local recurrences (16% versus 2.7%) and a number of metastases in sentinel lymph nodes (44% versus 22%) were significantly higher and a 5-year survival was significantly lower (64% versus 87.5%) in patients with residual melanoma. Breslow thickness, ulceration, positive SLNB and residual melanoma were independent prognostic factors for overall survival., Conclusions: Residual melanoma is very rare after an excisional biopsy of the primary melanoma. However, when present it indicates a higher probability of local recurrence and a worse overall survival., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Carotid paragangliomas are usually slowly enlarging and painless lateral neck masses. These mostly benign lesions are recognized due to their typical location, vessel displacement and specific blood supply, features that are usually seen on different imaging modalities. Surgery for carotid paraganglioma can be associated with immediate cerebrovascular complications or delayed neurological impairment.We are reporting the case of a 36-year-old man who presented with a painless mass on the right side of his neck 11 months after being treated for testicular cancer. After a fine-needle aspiration biopsy, he was diagnosed with a testicular cancer lymph node metastasis. Neck US and fluorine [F-18]-fluorodeoxy-D-glucose (FDG) PET-CT showed no signs of hypervascularity or vessel displacement. The patient underwent a level II to V functional neck dissection. During the procedure, suspicion of a carotid paraganglioma was raised and the tumour was carefully dissected from the walls of the carotid arteries with minimal blood loss and no cranial nerve dysfunction.The histology report revealed carotid paraganglioma with no metastasis in the rest of the lymph nodes. The patient's history of testicular germ cell tumour led to a functional neck dissection during which a previously unrecognized carotid paraganglioma was removed.Surgery for carotid PG can be associated with complications that have major impact on quality of life. A thorough assessment of the patient and neck mass must therefore be performed preoperatively in order to perform the surgical procedure under optimal conditions.