Far-Ultraviolet Radiation from Elliptical Galaxies

Far-ultraviolet radiation is a ubiquitous, if unanticipated, phenomenon in elliptical galaxies and early-type spiral bulges. It is the most variable photometric feature associated with old stellar populations. Recent observational and theoretical evidence shows that it is produced mainly by low-mass, small-envelope, helium-burning stars in extreme horizontal branch and subsequent phases of evolution. These are probably descendents of the dominant, metal rich population of the galaxies. Their lifetime UV outputs are remarkably sensitive to their physical properties and hence to the age and the helium and metal abundances of their parents. UV spectra are therefore exceptionally promising diagnostics of old stellar populations, although their calibration requires a much improved understanding of giant branch mass loss, helium enrichment, and atmospheric diffusion.Comment: 46 pages; includes LaTeX text file, 9 PS figures, 1 JPG figure, 2 style files. Full resolution figures and PS version available at http://www.astro.virginia.edu/~rwo/araa99/. Article to appear in Annual Reviews of Astronomy & Astrophysics, 199

The primordial Helium-4 abundance determination: systematic effects

By extrapolating to O/H = N/H = 0 the empirical correlations Y-O/H and Y-N/H defined by a relatively large sample of ~ 45 Blue Compact Dwarfs (BCDs), we have obtained a primordial 4Helium mass fraction Yp= 0.2443+/-0.0015 with dY/dZ = 2.4+/-1.0. This result is in excellent agreement with the average Yp= 0.2452+/-0.0015 determined in the two most metal-deficient BCDs known, I Zw 18 (Zsun/50) and SBS 0335-052 (Zsun/41), where the correction for He production is smallest. The quoted error (1sigma) of < 1% is statistical and does not include systematic effects. We examine various systematic effects including collisional excitation of Hydrogen lines, ionization structure and temperature fluctuation effects, and underlying stellar HeI absorption, and conclude that combining all systematic effects, our Yp may be underestimated by ~ 2-4%. Taken at face value, our Yp implies a baryon-to-photon number ratio eta = 4.7x10^-10 and a baryon mass fraction Omega_b h^2_{100} = 0.017+/-0.005 (2sigma), consistent with the values obtained from deuterium and Cosmic Microwave Background measurements. Correcting Yp upward by 2-4% would make the agreement even better.Comment: 12 pages, 5 PS figures, to appear in "Matter in the Universe", ed P. Jetzer, K. Pretzl and R. von Steiger, Kluwer, Dordrecht (2002

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

BACKGROUND: High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. METHODS: Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m(2)/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m(2)/d IV 5 days/week × 4 weeks followed by 10 MU/m(2 )subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. RESULTS: The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m(2)/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m(2)/week) (p = 0.003). CONCLUSION: Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited

MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1

© 2018 The Author(s). Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking

Evaluation of a new arterial pressure-based cardiac output device requiring no external calibration

<p>Abstract</p> <p>Background</p> <p>Several techniques have been discussed as alternatives to the intermittent bolus thermodilution cardiac output (CO_PAC) measurement by the pulmonary artery catheter (PAC). However, these techniques usually require a central venous line, an additional catheter, or a special calibration procedure. A new arterial pressure-based cardiac output (CO_AP) device (FloTrac™, Vigileo™; Edwards Lifesciences, Irvine, CA, USA) only requires access to the radial or femoral artery using a standard arterial catheter and does not need an external calibration. We validated this technique in critically ill patients in the intensive care unit (ICU) using CO_PACas the method of reference.</p> <p>Methods</p> <p>We studied 20 critically ill patients, aged 16 to 74 years (mean, 55.5 ± 18.8 years), who required both arterial and pulmonary artery pressure monitoring. CO_PACmeasurements were performed at least every 4 hours and calculated as the average of 3 measurements, while CO_APvalues were taken immediately at the end of bolus determinations. Accuracy of measurements was assessed by calculating the bias and limits of agreement using the method described by Bland and Altman.</p> <p>Results</p> <p>A total of 164 coupled measurements were obtained. Absolute values of CO_PACranged from 2.80 to 10.80 l/min (mean 5.93 ± 1.55 l/min). The bias and limits of agreement between CO_PACand CO_APfor unequal numbers of replicates was 0.02 ± 2.92 l/min. The percentage error between CO_PACand CO_APwas 49.3%. The bias between percentage changes in CO_PAC(ΔCO_PAC) and percentage changes in CO_AP(ΔCO_AP) for consecutive measurements was -0.70% ± 32.28%. CO_PACand CO_APshowed a Pearson correlation coefficient of 0.58 (<it>p </it>< 0.01), while the correlation coefficient between ΔCO_PACand ΔCO_APwas 0.46 (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Although the CO_APalgorithm shows a minimal bias with CO_PACover a wide range of values in an inhomogeneous group of critically ill patients, the scattering of the data remains relative wide. Therefore, the used algorithm (V 1.03) failed to demonstrate an acceptable accuracy in comparison to the clinical standard of cardiac output determination.</p

Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction

Aims: A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (= renin-angiotensin-system inhibitors) and β-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women. Methods: This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected. Results: Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p 100% of the new hypothetical target dose would be 24% for β-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed. Conclusion: In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance

Stent tunnel technique to save thrombosed native hemodialysis fistula with extensive venous aneurysm

Introduction and purpose: The increasing number of patients undergoing hemodialysis and the limited number of access sites have resulted in an increasing number of techniques to maintain vascular access for hemodialysis. Thrombosed arteriovenous (AV) fistulas with large venous aneurysms have poor treatment results, with both endovascular and surgical techniques, leading to a high rate of definitive AV access loss. The purpose of this study was to review the feasibility and initial results of this novel endovascular treatment of thrombosed AV fistulas with large venous aneurysms. Materials and methods: A novel endovascular treatment technique of inserting nitinol auto-expandable uncovered stents stretching through the whole puncture site area, thus creating a tunnel inside the thrombus, was retrospectively analyzed and described. Results: A total of 17 stents were placed in 10 hemodialysis fistulas, with a mean venous coverage length of 17.8 cm. In all the cases, 100% technical success was achieved, with complete restoration of blood flow in all patients. There were no procedure-related complications. The mean follow-up was 167 days (range 60–420 days), with a primary and assisted patency of 80% and 100%, respectively. No multiple trans-stent struts-related complications were observed. Three stent fractures were diagnosed with plain films at the site of puncture without consequence in the venous access permeability. Conclusion: The “stent tunnel technique” is a feasible, safe and effective alternative to salvage native hemodialysis access, thus extending the function of the venous access with no signs of stent-related complications and a respectable midterm patency

Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy

INTRODUCTION: The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer. METHODS: Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy. RESULTS: Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression. CONCLUSION: Therapeutic targets enabling the appearance of an endocrine responsive disease may increase treatment options for patients with breast cancer. Furthermore, these clinical data suggest that an ER-negative phenotype is a multi-step process with a reversible repression modality, and that some ER-negative tumors may either revert to an ER-positive phenotype, allowing an endocrine treatment to be effective

Photon Reabsorption in Mixed CsPbCl3_{3}:CsPbI3_{3} Perovskite Nanocrystal Films for Light-Emitting Diodes

Cesium lead halide nanocrystals, CsPbX$_{3}$ (X = Cl, Br, I), exhibit photoluminescence quantum efficiencies approaching 100% without the core-shell structures usually used in conventional semiconductor nanocrystals. These high photoluminescence efficiencies make these crystals ideal candidates for light-emitting diodes (LEDs). However, because of the large surface area to volume ratio, halogen exchange between perovskite nanocrystals of different compositions occurs rapidly, which is one of the limiting factors for white-light applications requiring a mixture of different crystal compositions to achieve a broad emission spectrum. Here, we use mixtures of chloride and iodide CsPbX$_{3}$ (X = Cl, I) perovskite nanocrystals where anion exchange is significantly reduced. We investigate samples containing mixtures of perovskite nanocrystals with different compositions and study the resulting optical and electrical interactions. We report excitation transfer from CsPbCl$_{3}$ to CsPbI$_{3}$ in solution and within a poly(methyl methacrylate) matrix via photon reabsorption, which also occurs in electrically excited crystals in bulk heterojunction LEDs.N.J.L.K.D. thanks the Cambridge Commonwealth European and International Trust, Cambridge Australian Scholarships, and Charles K. Allen for financial support. M.T. thanks the Gates Cambridge Trust, EPSRC, and the Winton Programme for the Physics of Sustainability for financial support. J.R. thanks the Cambridge Commonwealth European and International Trust, EPSRC and the Winton Programme for the Physics of Sustainability for financial support. E.P.B. thanks the EPSRC Centre for Doctoral Training: New and Sustainable Photovoltaics. R.D.L. thanks the EPSRC for funding. S.M.M. acknowledges competitive research funding from King Abdullah University of Science and Technology (KAUST). F.W.R.R. gratefully thanks financial support from CNPq Grant No. 246050/2012-8. F.W.R.R. and C.D. acknowledge funding from the ERC under Grant No. 259619 PHOTO-EM. C.D. acknowledges financial support from the EU under Grant No. 312483 ESTEEM2. F.D. is thankful for the Herchel Smith fellowship. This work was supported by the EPSRC (Grant Nos. EP/M005143/1, EP/G060738/1, and EP/G037221/1)