Negative HER2/neu amplification using immunohistochemistry and chromogenic in situ hybridization techniques in skin melanoma cases

Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age 57.9±19.5 years were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/ neu was negative in 97.5 of patients with IHC and in 100 of patients with CISH technique. Only one case (2.5) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47 of cases were in Clark level III, while the mean of Breslow thickness was 3.56±2.87 mm. The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques

Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial

Objectives: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. Methods: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/−anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. Results: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. Conclusions: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number: NCT0243318

Detection of splenic microabscesses with ultrasound as a marker for extrapulmonary tuberculosis in patients with HIV: A systematic review

Background. In 2015, 1.2 million new cases of tuberculosis (TB) were diagnosed in patients with HIV. Diagnostic limitations and resource shortages in endemic areas can delay diagnosis and treatment, particularly with extrapulmonary TB (EPTB). Research suggests that ultrasound can identify splenic microabscesses caused by EPTB, but data are limited on the frequency of this finding in patients with culture-proven EPTB.Objectives. To estimate the frequency of splenic EPTB microabscesses detected with ultrasound in patients with HIV and TB co-infection.Methods. Studies published in six major databases as of November 2017 were systematically reviewed based on the PRISMA guidelines. Cohen’s kappa test was used to determine inter-rater agreement. Articles included for data abstraction passed the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) evaluation. Freeman-Tukey transformation was used to calculate weighted proportions. Heterogeneity was evaluated by Forest plot and I2 calculation.Results. After abstract screening, article review and QUADAS-2 evaluation, five studies were selected for data extraction. A total of 774 patients in these studies were infected with HIV. Splenic lesions were seen with ultrasound in 21.0% of patients with HIV (95% confidence interval (CI) 10.6 - 33.8). TB diagnosed by culture, biopsy, smear, or molecular methods was found to be the cause of 88.3% (95% CI 72.3 - 97.9) of splenic microabscesses seen on ultrasound in patients with HIV.Conclusions. Ultrasound evaluation of the spleen in patients with HIV and symptoms suggestive of TB in endemic regions is a viable diagnostic adjunct. Ultrasound detection of splenic microabscesses in HIV patients is probably sufficient indication to initiate TB treatment prior to obtaining culture data. Strong conclusions cannot be drawn owing to the high heterogeneity of this small number of studies.

First Detection of Polarization of the Submillimetre Diffuse Galactic Dust Emission by Archeops

We present the first determination of the Galactic polarized emission at 353 GHz by Archeops. The data were taken during the Arctic night of February 7, 2002 after the balloon--borne instrument was launched by CNES from the Swedish Esrange base near Kiruna. In addition to the 143 GHz and 217 GHz frequency bands dedicated to CMB studies, Archeops had one 545 GHz and six 353 GHz bolometers mounted in three polarization sensitive pairs that were used for Galactic foreground studies. We present maps of the I, Q, U Stokes parameters over 17% of the sky and with a 13 arcmin resolution at 353 GHz (850 microns). They show a significant Galactic large scale polarized emission coherent on the longitude ranges [100, 120] and [180, 200] deg. with a degree of polarization at the level of 4-5%, in agreement with expectations from starlight polarization measurements. Some regions in the Galactic plane (Gem OB1, Cassiopeia) show an even stronger degree of polarization in the range 10-20%. Those findings provide strong evidence for a powerful grain alignment mechanism throughout the interstellar medium and a coherent magnetic field coplanar to the Galactic plane. This magnetic field pervades even some dense clouds. Extrapolated to high Galactic latitude, these results indicate that interstellar dust polarized emission is the major foreground for PLANCK-HFI CMB polarization measurement.Comment: Submitted to Astron. & Astrophys., 14 pages, 12 Fig., 2 Table

Computer-aided dermoscopy for diagnosis of melanoma

BACKGROUND: Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients. METHODS: We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM(® )dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically. RESULTS: Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%. CONCLUSION: The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions

Fast-Response Calmodulin-Based Fluorescent Indicators Reveal Rapid Intracellular Calcium Dynamics

Faithful reporting of temporal patterns of intracellular Ca 2 + dynamics requires the working range of indicators to match the signals. Current genetically encoded calmodulin-based fluorescent indicators are likely to distort fast Ca 2 + signals by apparent saturation and integration due to their limiting fluorescence rise and decay kinetics. A series of probes was engineered with a range of Ca 2 + affinities and accelerated kinetics by weakening the Ca 2 + -calmodulin-peptide interactions. At 37 °C, the GCaMP3-derived probe termed GCaMP3 fast is 40-fold faster than GCaMP3 with Ca 2 + decay and rise times, t 1/2 , of 3.3 ms and 0.9 ms, respectively, making it the fastest to-date. GCaMP3 fast revealed discreet transients with significantly faster Ca 2 + dynamics in neonatal cardiac myocytes than GCaMP6f. With 5-fold increased two-photon fluorescence cross-section for Ca 2 + at 940 nm, GCaMP3 fast is suitable for deep tissue studies. The green fluorescent protein serves as a reporter providing important novel insights into the kinetic mechanism of target recognition by calmodulin. Our strategy to match the probe to the signal by tuning the affinity and hence the Ca 2 + kinetics of the indicator is applicable to the emerging new generations of calmodulin-based probe

Search for charginos in e+e- interactions at sqrt(s) = 189 GeV

An update of the searches for charginos and gravitinos is presented, based on a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by combining the chargino searches with neutralino searches at the Z resonance implies a limit on the mass of the lightest neutralino which, for a heavy sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure

Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV

The DELPHI detector at LEP has collected 54 pb^{-1} of data at a centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data were used to measure the average charged particle multiplicity in e+e- -> b bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183 GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85 (stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01 (syst). This result is consistent with QCD predictions, while it is inconsistent with calculations assuming that the multiplicity accompanying the decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio