A DETAILED PHOTOMETRIC AND SPECTROSCOPIC STUDY OF THE 2011 OUTBURST OF THE RECURRENT NOVA T Pyxidis FROM 0.8 TO 250 DAYS AFTER DISCOVERY

We investigated the optical light curve of T Pyx during its 2011 outburst through compiling a database of Solar Mass Ejection Imager (SMEI) and AAVSO observations. The SMEI light curve, providing unprecedented detail covering t=1.5-49 days post-discovery, was divided into four phases based on the idealised nova optical light curve; the initial rise (1.5-3.3 days), the pre-maximum halt (3.3-13.3 days), the final rise (14.7-27.9 days), and the early decline (27.9 days - -). The SMEI light curve contains a strongly detected period of 1.44_0.05 days during the pre-maximum halt phase. These oscillations resemble those found in recent TNR models arising from instabilities in the expanding envelope. No spectral variations that mirror the light curve periodicity were found however. The marked dip at t_22-24 days just before light curve maximum at t=27.9 days may represent the same (shorter duration) phenomenon seen in other novae observed by SMEI and present in some model light curves. The spectra from the 2m Liverpool Telescope and SMARTS 1.5m telescope were obtained from t=0.8-80.7 and 155.1-249.9 days, covering the major phases of development. The nova was observed very early in its rise where a distinct high velocity ejection phase was evident with derived Vej_4000 km

Spectroscopic and Photometric Development of T Pyxidis (2011) from 0.8 to 250 Days After Discovery

We investigated the optical light curve of T Pyx during its 2011 outburst through compiling a database of SMEI and AAVSO observations. The SMEI light curve, providing unprecedented detail with high cadence data during t=1.5-49 days post-discovery, was divided into four phases based on the idealised nova optical light curve; the initial rise, the pre-maximum halt (or the 'plateau'), the final rise, and the early decline. Variation in the SMEI light curve reveals a strongly detected period of 1.44\pm0.04 days before the visual maximum. The spectra from the LT and SMARTS telescopes were investigated during t=0.8-80.7 and 155.1-249.9 days. The nova was observed very early in its rise and a distinct high velocity ejection phase was evident. A marked drop and then gradual increase in derived ejection velocities were present. Here we propose two different stages of mass loss, a short-lived phase occurring immediately after outburst followed by a more steadily evolving and higher mass loss phase. The overall spectral development follows that typical of a Classical Nova and comparison to the photometric behaviour reveals consistencies with the simple evolving pseudo-photosphere model of the nova outburst. The optical spectra are also compared to X-ray and radio light curves. Weak [Fe X] 6375A emission was marginally detected before the rise in X-ray emission. The middle of the plateau in the X-ray light curve is coincident with the appearance of high ionization species detected in optical spectra and the peak of the high frequency radio flux

Nova light curves from the Solar Mass Ejection Imager (SMEI) - II. The extended catalog

We present the results from observing nine Galactic novae in eruption with the Solar Mass Ejection Imager (SMEI) between 2004 and 2009. While many of these novae reached peak magnitudes that were either at or approaching the detection limits of SMEI, we were still able to produce light curves that in many cases contained more data at and around the initial rise, peak, and decline than those found in other variable star catalogs. For each nova, we obtained a peak time, maximum magnitude, and for several an estimate of the decline time (t2). Interestingly, although of lower quality than those found in Hounsell et al. (2010a), two of the light curves may indicate the presence of a pre-maximum halt. In addition the high cadence of the SMEI instrument has allowed the detection of low amplitude variations in at least one of the nova light curves

No neon, but jets in the remarkable recurrent nova M31N 2008-12a? - Hubble Space Telescope spectroscopy of the 2015 eruption

The 2008 discovery of an eruption of M31N 2008-12a began a journey on which the true nature of this remarkable recurrent nova continues to be revealed. M31N 2008-12a contains a white dwarf close to the Chandrasekhar limit, accreting at a high rate from its companion, and undergoes thermonuclear eruptions which are observed yearly and may even be twice as frequent. In this paper, we report on Hubble Space Telescope STIS UV spectroscopy taken within days of the predicted 2015 eruption, coupled with Keck spectroscopy of the 2013 eruption. Together, this spectroscopy permits the reddening to be constrained to E(B-V) = 0.10 +/- 0.03. The UV spectroscopy reveals evidence for highly ionized, structured, and high velocity ejecta at early times. No evidence for neon is seen in these spectra however, but it may be that little insight can be gained regarding the composition of the white dwarf (CO vs ONe)

No neon, but jets in the remarkable recurrent nova M31N 2008-12a? - Hubble Space Telescope spectroscopy of the 2015 eruption

The 2008 discovery of an eruption of M31N 2008-12a began a journey on which the true nature of this remarkable recurrent nova continues to be revealed. M31N 2008-12a contains a white dwarf close to the Chandrasekhar limit, accreting at a high rate from its companion, and undergoes thermonuclear eruptions which are observed yearly and may even be twice as frequent. In this paper, we report on Hubble Space Telescope STIS UV spectroscopy taken within days of the predicted 2015 eruption, coupled with Keck spectroscopy of the 2013 eruption. Together, this spectroscopy permits the reddening to be constrained to E(B-V) = 0.10 +/- 0.03. The UV spectroscopy reveals evidence for highly ionized, structured, and high velocity ejecta at early times. No evidence for neon is seen in these spectra however, but it may be that little insight can be gained regarding the composition of the white dwarf (CO vs ONe)

Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol

Gene therapy is a potential method of treating cancer with a greater degree of targeting than conventional therapies. In addition, therapy can be directed towards cells within the tumour population that are traditionally resistant to current treatment schedules. Horseradish peroxidase (HRP) can oxidise paracetamol to N-acetyl-p-benzoquinoneimine via a one-electron pathway. Incubation of human cells expressing HRP with 0.5–10 mm paracetamol reduced clonogenic survival, but had little effect on control cells. A small increase in apoptosis was seen and a decrease in the number of cells undergoing mitosis, consistent with reports in hepatocytes using higher paracetamol concentrations. The cytotoxicity was also seen under conditions of severe hypoxia (catalyst induced anoxia), indicating that the HRP/paracetamol combination may be suitable for hypoxia-targeted gene therapy

Premature Decline of Serum Total Testosterone in HIV-Infected Men in the HAART-Era

BackgroundTestosterone (T) deficiency remains a poorly understood issue in men with Human Immunodeficiency Virus (HIV). We investigated the gonadal status in HIV-infected men in order to characterize T deficiency and to identify predictive factors for low serum T.Methodology/Principal FindingsWe performed a cross-sectional, observational study on 1325 consecutive HIV male outpatients, most of them having lipodystrophy. Serum total T<300 ng/dL was used as the threshold for biochemical T deficiency. Morning serum total T, luteinizing hormone (LH), estradiol, HIV parameters, and body composition parameters by CT-scan and Dual-Energy-X-ray-Absorptiometry were measured in each case. Sexual behavior was evaluated in a subset of 247 patients. T deficiency was found in 212 subjects, especially in the age range 40\u201359, but was frequent even in younger patients. T deficiency occurred mainly in association with low/normal serum LH. Adiposity was higher in subjects with T deficiency (p<0.0001) and both visceral adipose tissue and body mass index were the main negative predictors of serum total T. Osteoporosis and erectile dysfunction were present in a similar percentage in men with or without T deficiency.Conclusions/SignificancePremature decline of serum T is common (16%) among young/middle-aged HIV-infected men and is associated with inappropriately low/normal LH and increased visceral fat. T deficiency occurs at a young age and may be considered an element of the process of premature or accelerated aging known to be associated with HIV infection. The role of HIV and/or HIV infection treatments, as well as the role of the general health state on the gonadal axis, remains, in fact, to be elucidated. Due to the low specificity of signs and symptoms of hypogonadism in the context of HIV, caution is needed in the diagnosis of hypogonadism in HIV-infected men with biochemical low serum T levels

Urban signals in high-resolution weather and climate simulations: role of urban land-surface characterisation

Two urban schemes within the Joint UK Land Environment Simulator (JULES) are evaluated offline against multi-year flux observations in the densely built-up city centre of London and in suburban Swindon (UK): (i) the 1-tile slab model, used in climate simulations, (ii) the 2-tile canopy model MORUSES (Met Office–Reading Urban Surface Exchange Scheme), used for numerical weather pre- diction over the UK. Offline, both models perform better at the suburban site, where differences between the urban schemes are less pronounced due to larger vegetation fractions. At both sites, the outgoing short- and longwave radiation is more accurately represented than the turbulent heat fluxes. The seasonal varia- tions of model skill are large in London, where the sensible heat flux in autumn and winter is strongly under-predicted if the large city-centre magnitudes of anthro- pogenic heat emissions are not represented. The delayed timing of the sensible heat flux in the 1-tile model in London results in large negative bias in the morning. The partitioning of the urban surface into canyon and roof in MORUSES improves this as the roof-tile is modelled with a very low thermal inertia, but phase and amplitude of the gridbox-averaged flux critically depend on accurate knowledge of the plan-area fractions of streets and buildings. Not representing non-urban land- cover (e.g. vegetation, inland water) in London results in severely under-predicted latent heat fluxes. Control runs demonstrate that the skill of both models can be greatly improved by providing accurate land-cover and morphology information and using representative anthropogenic heat emissions, which is essential if the model output is intended to inform integrated urban services

Core outcome domains for early-phase clinical trials of sound-, psychology-, and pharmacology-based interventions to manage chronic subjective tinnitus in adults: the COMIT'ID study protocol for using a Delphi process and face-to-face meetings to establish consensus

Background: The reporting of outcomes in clinical trials of subjective tinnitus indicates that many different tinnitus-related complaints are of interest to investigators, from perceptual attributes of the sound (e.g. loudness) to psychosocial impacts (e.g. quality of life). Even when considering one type of intervention strategy for subjective tinnitus, there is no agreement about what is critically important for deciding whether a treatment is effective. The main purpose of this observational study is therefore to develop Core Outcome Domain Sets for the three different intervention strategies (sound, psychological, and pharmacological) for adults with chronic subjective tinnitus that should be measured and reported in every clinical trial of these interventions. Secondary objectives are to identify the strengths and limitations of our study design for recruiting and reducing attrition of participants, and to explore uptake of the core outcomes. Methods: The ‘Core Outcome Measures in Tinnitus: International Delphi’ (COMIT’ID) study will use a mixed methods approach that incorporates input from healthcare users at the pre-Delphi stage, a modified three round Delphi survey and final consensus meetings (one for each intervention). The meetings will generate recommendations by stakeholder representatives on agreed Core Outcome Domain Sets specific to each intervention. A subsequent step will establish a common cross-cutting Core Outcome Domain Set by identifying the common outcome domains included in all three intervention-specific Core Outcome Domain Sets. To address the secondary objectives, we will gather feedback from participants about their experience of taking part in the Delphi process. We aspire to conduct an observational cohort study to evaluate uptake of the core outcomes in published studies at 7 years following core outcome set publication. Discussion: The COMIT’ID study aims to develop a Core Outcome Domain Set that are agreed as critically important for deciding whether a treatment for subjective tinnitus is effective. Such a recommendation would help to standardise future clinical trials worldwide and so we will determine if participation increases use of the core outcome set in the long term. Trial registration: This project has been registered in the database of the Core Outcome Measures in Effectiveness Trials (COMET) initiative

Serotonin regulates prostate growth through androgen receptor modulation

Serotonin regulates prostate growth through androgen receptor modulationAging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT's inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT's inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.Projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and Bolsa de Investigação GSK Inovação em Urologia 2012info:eu-repo/semantics/publishedVersio