On combining the beam path of similar wavelength lasers for dual-laser Thomson scattering.

A novel method for the path combination of two lasers with very similar wavelengths has been implemented to enable the evaluation of a dual-laser calibration Thomson scattering (TS) technique. The first experimental test of this TS technique has been performed in a RFX-mod plasma device, where, due to experimental constraints, the combination of a Nd:YAG (λ = 1064 nm) and a Nd:YLF (λ = 1053 nm) laser system was the only viable choice available. The method requires that the beam path of both lasers be combined into a single path with the same polarization. This presents a unique challenge due to the small difference between the two laser wavelengths. In this paper, we describe two methods for beam combination: first via a prism, eventually dismissed as unpractical, and second via a polarizing beam splitter in reverse with a dual-wavelength waveplate. We detail the optical setup, waveplate design, and successful implementation of this second method.

Design of JT-60SA core Thomson scattering diagnostic system.

An incoherent Thomson scattering diagnostic will be installed in the JT-60SA tokamak to measure electron temperature and electron density profiles. The target radial spatial resolution is 25 mm with 46 spatial channels. The accuracy in electron temperature and density is a few percent at ne = 7.5 × 1019 m-3, which is the expected value in the plasma core. This paper presents the designs of collection optics, fibers with their alignment system, and polychromators. The collection optics overcomes unique issues for superconducting fusion devices, i.e., limited design space, high-temperature measurements, and harsh radiation condition. When in several years the more performing plasma will generate intense nuclear radiation, the lens materials of the optics can be replaced by radiation resistant glasses without major changes in the lens holder. It will prevent transmission degradation and keep stable measurement accuracy.

CRISP: A compact RF ion source prototype for emittance scanner testing.

A movable Allison type emittance scanner is being developed to characterize the phase-space distribution of the beamlets of spectral phase interferometry for direct electric-field reconstruction, the prototype RF negative ion source of the ITER heating neutral beam injector. To test the electronics and verify the capability of the device to resolve nearby beamlets, a compact RF ion source prototype has been set up, capable of accelerating 1 mA of helium ions up to a voltage of 2 kV. A commercial 100 W RF generator creates a plasma inside a Pyrex tube, with a density between 1015 and 1016 m-3 and an electron temperature up to 15 eV. Three multi-aperture grids in accel-decel configuration extract and accelerate the ions, which are measured with a Faraday cup. We present in this paper the characterization of the ion source and its first operation, showing that it is suitable for the commissioning of the Allison scanner.

Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer.

Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22-0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.

Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. DESIGN: Retrospective cohort study with stepwise forward logistic regression analysis of results. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. RESULTS: Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

Internal Transport Barrier Broadening through Subdominant Mode Stabilization in Reversed Field Pinch Plasmas.

The reversed field pinch (RFP) device RFX-mod features strong internal transport barriers when the plasma accesses states with a single dominant helicity. Such transport barriers enclose a hot helical region with high confinement whose amplitude may vary from a tiny one to an amplitude encompassing an appreciable fraction of the available volume. The transition from narrow to wide thermal structures has been ascribed so far to the transport reduction that occurs when the dominant mode separatrix, which is a preferred location for the onset of stochastic field lines, disappears. In this Letter we show instead that the contribution from the separatrix disappearance, by itself, is marginal and the main role is instead played by the progressive stabilization of secondary modes. The position and the width of the stochastic boundary encompassing the thermal structures have been estimated by applying the concept of a 3D quasiseparatrix layer, developed in solar physics to treat reconnection phenomena without true separatrices and novel to toroidal laboratory plasmas. Considering the favorable scaling of secondary modes with the Lundquist number, these results open promising scenarios for RFP plasmas at temperatures higher than the presently achieved ones, where lower secondary modes and, consequently, larger thermal structures are expected. Furthermore, this first application of the quasiseparatrix layer to a toroidal plasma indicates that such a concept is ubiquitous in magnetic reconnection, independent of the system geometry under investigation.

A feasibility study of a NBI photoneutralizer based on nonlinear gating laser recirculation.

The neutralization efficiency of negative ion neutral beam injectors is a major issue for future fusion reactors. Photon neutralization might be a valid alternative to present gas neutralizers, but still with several challenges for a valid implementation. Some concepts have been presented so far but none has been validated yet. A novel photoneutralization concept is discussed here, based on an annular cavity and a duplicated frequency laser beam (recirculation injection by nonlinear gating). The choice of lithium triborate as the material for the second harmonic extractor is discussed and a possible cooling method via crystal slicing is presented; laser intensity enhancement within the cavity is evaluated in order to quantify the achievable neutralization rate. Mockups of the critical components are proposed as intermediate steps toward system realization.

Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

An analysis of different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia: a single-centre experience.

CONTEXT: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of Cushing's syndrome (CS). A variety of in vivo tests to identify aberrant receptor expression have been proposed to guide medical treatment. Unilateral adrenalectomy (UA) may be effective in selected patients, but little is known about recurrence during follow-up. OBJECTIVE: To describe a series of patients with BMAH and CS treated by different approaches, with a particular focus on the benefit of UA. DESIGN AND PATIENTS: We retrospectively assessed 16 patients with BMAH and CS (11 females, five males), analysing the in vivo cortisol response to different provocative tests. Twelve of the 16 patients underwent UA and were monitored over the long term. RESULTS: Based on in vivo test results, octreotide LAR or propranolol was administered in one case of food-dependent CS and two patients with a positive postural test. A significant improvement in biochemical values was seen in all patients but with limited clinical response. UA was performed in 12 patients, producing long-term remission in three (106 ± 28 months; range: 80-135), recurrence in eight (after 54 ± 56 months; range 12-180) and persistence in one other. Four patients subsequently underwent contralateral adrenalectomy for overt CS, one received ketoconazole, and four other patients remain under observation for subclinical CS. CONCLUSIONS: Medical treatment based on cortisol response to provocative tests had a limited role in our patients, whereas UA was useful in some of them. Although recurrence is likely, the timing of onset is variable and close follow-up is mandatory to identify it.

Dual-angle, self-calibrating Thomson scattering measurements in RFX-MOD.

In the multipoint Thomson scattering (TS) system of the RFX-MOD experiment the signals from a few spatial positions can be observed simultaneously under two different scattering angles. In addition the detection system uses optical multiplexing by signal delays in fiber optic cables of different length so that the two sets of TS signals can be observed by the same polychromator. Owing to the dependence of the TS spectrum on the scattering angle, it was then possible to implement self-calibrating TS measurements in which the electron temperature Te, the electron density ne and the relative calibration coefficients of spectral channels sensitivity Ci were simultaneously determined by a suitable analysis of the two sets of TS data collected at the two angles. The analysis has shown that, in spite of the small difference in the spectra obtained at the two angles, reliable values of the relative calibration coefficients can be determined by the analysis of good S/N dual­angle spectra recorded in a few tens of plasma shots. This analysis suggests that in RFX-MOD the calibration of the entire set of TS polychromators by means of the similar, dual-laser (Nd:YAG/Nd:YLF) TS technique, should be feasible.

Edge Thomson scattering diagnostic on COMPASS tokamak: installation, calibration, operation, improvements.

The core Thomson scattering diagnostic (TS) on the COMPASS tokamak was put in operation and reported earlier. Implementation of edge TS, with spatial resolution along the laser beam up to ∼1/100 of the tokamak minor radius, is presented now. The procedure for spatial calibration and alignment of both core and edge systems is described. Several further upgrades of the TS system, like a triggering unit and piezo motor driven vacuum window shutter, are introduced as well. The edge TS system, together with the core TS, is now in routine operation and provides electron temperature and density profiles.

Experimental observation of microtearing modes in a toroidal fusion plasma.

Experimental evidences of short wavelength electromagnetic modes are found in the reversed-field-pinch configuration device RFX-mod by means of in-vessel magnetic probes. The modes are revealed during the helical states of the plasma. Their amplitude is well correlated to the electron temperature gradient strength in the core. On the basis of linear gyrokinetic calculations we interpret these instabilities as microtearing modes.

The UEMS section/board of pathology, chapter 6: requirement for recognition of postgraduate training in pathology: a presentation of the paris document.

After more than five years discussion the UEMS Section/Board of Pathology agreed a specification of requirements for recognition of post-graduate training in pathology, which is the key to the future of our discipline. The document published here, subject to ratification by UEMS Council, was voted on and accepted by the Pathology Board at the UEMS Paris meeting of 9 June 2012. Cytopathology is regarded as integral part of pathology: in general, training in pathology takes five years and maintains a common trunk of four (minimum three) years where surgical pathology, autopsy pathology and basic knowledge of neuropathology, dermatopathology and cytopathology are adequately trained and assessed. Training in so-called 'areas of interests' covers the remaining 12-24 months. Certificates of 'advanced level of competence' remain within the authority of national boards. As senior members of its Executive Board, we believe that the European Federation of Cytology Societies (EFCS) should take responsibility for establishing 1) standards in the quality of cytopathology training, 2) training guidelines and qualification for advanced levels of competence in cytopathology, 3) manpower planning, 4) tutorials for pathologists and cytotechnologists and 4) standards of cytotechnologist training.

Fine needle aspiration of non-small cell lung cancer: current state and future perspective.

AThe emerging treatment revolution determined by the advent of new targeted therapies requires accurate tumour subtyping as a mandatory step in the clinical workup of patients with non-small cell lung carcinoma (NSCLC). As a result of advanced and inoperable disease or poor performance status, in many patients, minimally invasive procedures must be employed to obtain diagnostic material. Fine needle aspiration (FNA) is a valid and widely employed alternative to either tru-cut or open-sky biopsy. Indeed, cytological specimens are suitable for techniques such as immunocytochemistry, mutation and microRNA analysis, and may present advantages over small biopsies especially if cell blocks are prepared and attention is paid to cytomorphology and pre-analytic management of specimens at the time they are collected. These will allow the adequate stratification of patients into different diagnostic and prognostic classes.

The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells.

Somatic mutations in the GNAS1 gene, encoding the α-subunit of the heterotrimeric stimulatory G protein (Gαs), occur in approximately 40% of growth hormone (GH)-secreting pituitary tumours. By altering the adenylate cyclase-cAMP-protein kinase A pathway, they unequivocally give somatotroph cells a growth advantage. Hence, the pathogenesis of somatotropinomas could be linked to anomalies in receptors coupled to the cAMP second-messenger cascade. Among them, the glucose-dependent insulinotropic polypeptide receptor (GIPR) is already known to play a primary role in the impaired cAMP-dependent cortisol secretion in patients affected by food-dependent Cushing's syndrome. In the present study, 43 somatotropinomas and 12 normal pituitary glands were investigated for GIPR expression by quantitative reverse transcriptase-polymerase chain reaction, western blotting and immunohistochemistry. Tumoural specimens were also evaluated for GNAS1 mutational status. The effect of GIPR overexpression on cAMP levels and GH transcription was evaluated in an in vitro model of somatotropinomas, the GH-secreting pituitary cell line GH3. GIPR was expressed at higher levels compared to normal pituitaries in 13 GNAS1 mutation-negative somatotropinomas. GIP stimulated adenylyl cyclase and GH-promoter activity in GIPR-transfected GH3 cells, confirming a correct coupling of GIPR to Gαs. In a proportion of acromegalic patients, GIPR overexpression appeared to be associated with a paradoxical increase in GH after an oral glucose tolerance test. Whether GIPR overexpression in acromegalic patients may be associated with this paradoxical response or more generally involved in the pathogenesis of acromegaly, as suggested by the mutually exclusive high GIPR levels and GNAS1 mutations, remains an open question.