Telomere length predicts for outcome to FCR chemotherapy in CLL

We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0.0001; HR = 2.17) and shorter overall survival (OS) (P = 0.0002; HR = 2.44). Bifurcation of the IGHV-mutated and unmutated subsets according to telomere length revealed that patients with TL-IFR in each subset had shorter PFS (HR = 4.35 and HR = 1.48, respectively) and shorter OS (HR = 3.81 and HR = 2.18, respectively). In addition, the OS of the TL-OFR and TL-IFR subsets were not significantly altered by IGHV mutation status (P = 0.61; HR = 1.24 and P = 0.41; HR = 1.47, respectively). In multivariate modeling, telomere length was the dominant co-variable for PFS (P = 0.0002; HR = 1.85) and OS (P = 0.05; HR = 1.61). Taken together, our data suggest that HT-STELA is a powerful predictor of outcome to FCR-based treatment and could be used to inform the design of future risk-adapted clinical trials

Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

© 2014 John Wiley & Sons Ltd. Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P  <  0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI]  = 11·6-106·4) and this was preserved in early-stage disease patients (P  <  0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL

Annealing of irradiated n+p InP buried homojunctions

At the last SPRAT conference, the Naval Research Laboratory (NRL) presented results from two experiments. One studied n+p diffused junction (DJ) InP solar cells, and the other studied n+p shallow homojunction (SHJ) InP mesa diodes grown by metalorganic chemical vapor deposition (MOCVD). The former work showed that a DJ solar cell in which the maximum power P(sub max) had been degraded by nearly 80 percent under irradiation recovered completely under short circuit illumination at 450K. The recovery was accompanied by the removal of all but one of the radiation-induced defect levels. The latter work, on the other hand, showed that the radiation-induced defects in the SHJ diodes did not anneal until the temperature reached 650K. These results suggest that an irradiated DJ solar cell, under illumination, will anneal at a temperature 200K lower than an irradiated SHJ cell. This is an unexpected result considering the similarity of the devices. The goal of the present research is to explain this different behavior. This paper investigates two points which arose from the previous studies. The first point is that the DJ cells were annealed under illumination while the SHJ diodes were annealed without bias. The second point investigated here is that the emitters of the DJ and SHJ devices were significantly different

Prostanoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [644]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial

UNLABELLED: Graves Orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up. METHODS: 3 year follow-up of a subset of the CIRTED trial (N=68) which randomized patients to receive high dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. RESULTS: Data were available at 3 years from 68 of 126 randomised subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a Binary Clinical Composite Outcome Measure, modified EUGOGO score or Ophthalmopathy Index.Clinical Activity Score (CAS), Ophthalmopathy Index and Total Eye Score improved over 3 years (p<0.001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24/64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery OR=16.8 (95%CI 2.95, 95.0) p=0.001. Higher baseline levels of CAS, Ophthalmopathy Index and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery. CONCLUSION: In this long-term follow-up from a clinical trial, 3 year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes

A miniaturized 4 K platform for superconducting infrared photon counting detectors

We report on a miniaturized platform for superconducting infrared photon counting detectors. We have implemented a fibre-coupled superconducting nanowire single photon detector in a Stirling/Joule–Thomson platform with a base temperature of 4.2 K. We have verified a cooling power of 4 mW at 4.7 K. We report 20% system detection efficiency at 1310 nm wavelength at a dark count rate of 1 kHz. We have carried out compelling application demonstrations in single photon depth metrology and singlet oxygen luminescence detection

Prostanoid receptors (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [661]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Differences and similarities between human and rodent prostanoid receptor orthologues, and their specific roles in pathophysiologic conditions are reviewed in [423]. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

Prostanoid receptors (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [659]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

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