A case report: retigabine induced oral mucosal dyspigmentation of the hard palate

Background Dyspigmentation of the oral mucosa has a multitude of aetiological causes. Retigabine, a new antiepileptic drug, has the potential side effect of inducing a blue/purple pigmentation of the oral mucosa in addition to the skin, lips, nails and retina of the eyes. This article presents a unique case of dyspigmentation present in the oral mucosa of the hard palate which has previously been unreported in the dental literature. Case presentation A 70 year old white male presented to a secondary care oral surgery department with an unusual asymptomatic pigmented lesion present in the hard palate of the oral cavity. The pigmentation was remarkable for its distinct blue/purple colouration which was associated with a similar discolouration of the nail beds of the hands. This is believed to be a side effect of the anti-epileptic medication retigabine. Conclusion The dental profession and wider healthcare community should be made fully aware of the potential side effect of oral dyspigmentation associated with the novel anti-epileptic medication retigabine. Enhanced knowledge of the causative role of retigabine in dyspigementation of the oral mucosa will allow the practitioner to make an appropriate diagnosis. As far the authors are aware this is reaction is unreported in the dental literature and should be disseminated to the wider oral health professional’s community

Mortality post inpatient alcohol detoxification: a descriptive case series

<br>Background: Individuals with alcohol dependence often die prematurely. Scotland in particular has high rates of alcohol misuse compared to the rest of the UK and Europe. Although there is some evidence that rates of alcoholrelated harm and alcohol-related deaths are reducing in Europe, there is little evidence of this trend occurring in Scotland. Inpatient detoxification is an important, but expensive, option in the management of alcohol dependence. Little work has been done with regard possible clinical characteristics associated with mortality post discharge in this cohort of patients.</br> <br>Methods: Retrospective electronic records were used to identify patients admitted electively for alcohol detoxification into a psychiatric ward in a district general hospital under the care of a single consultant addiction psychiatrist between 1/1/05 and 31/12/07 inclusively. Demographic and clinical factors were recorded. 5-year mortality data was obtained by linkage to the National Records of Scotland.</br> <br>Results: 25.2% of patients admitted for elective alcohol detoxification died during the 5-year follow up period. 42.9% of deaths (n=12) were due to alcoholic liver disease, one death (3.6%) was of undetermined intent. A higher proportion of the deceased cohort was likely to have continued disulfiram (93% vs. 80%) and acamprosate (81% vs. 60%) than those surviving. There was no statistically significant difference in survival between individuals on medication and those not on medications in our cohort. The average consumption of units of alcohol per week in the deceased cohort was significantly higher than that calculated for the surviving cohort (298.8 units vs. 233.3 units p=0.0137).</br> <br>Conclusion: Inpatient detoxification was associated with significant mortality at 5-year follow up post- discharge. The majority of deaths were due to liver disease while deaths due to accidents and of undetermined intent were relatively infrequent. Increased education and practical strategies such as “space and pace” aimed both at an individual and societal level to reduce alcohol consumption may help to reduce mortality associated with alcohol dependence post inpatient detoxification.</br&gt

Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies

Introduction: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ≥65 years. Methods: Safety/tolerability and efficacy data for patients aged ≥65 years were pooled from three randomized, double-blind, placebo-controlled, fixed-dose Phase III studies (NCT00490035, NCT00464269, and NCT01261325). Data were pooled by treatment group: placebo or the proposed therapeutic dose range of 50–200 mg/day: BRV 50, 100, 200 mg/day. Results: Thirty-two patients aged ≥65 years were randomized to placebo or BRV 50–200 mg/day. Of these, 30 patients (93.8%) completed their respective study. In the safety population (n = 32), 87.5% placebo- vs 73.3% BRV-treated patients reported treatment-emergent adverse events (TEAEs) during the treatment period; most commonly, headache (25.0% vs 12.5%), paresthesia (0% vs 12.5%), and somnolence (50.0% vs 12.5%) for placebo- vs BRV-treated patients, respectively. During the treatment period, drug-related TEAEs were reported by 62.5% of placebo- vs 53.3% of BRV-treated patients, and serious TEAEs (SAEs) were reported by 0% of placebo- and 4.2% of BRV-treated patients; there were no drug-related SAEs and no deaths. Three SAEs (placebo 1/8; BRV 2/24) and two deaths (placebo 1/8; BRV 1/24) occurred in the post-treatment period. In the efficacy population (n = 31), median percent reduction from baseline in focal seizure frequency/28 days was 14.0% for placebo vs 25.5%, 49.6%, and 74.9% for BRV 50, 100, and 200 mg/day, respectively. The ≥50% responder rate was 14.3% for placebo vs 25.0%, 50.0%, and 66.7% for BRV 50, 100, and 200 mg/day, respectively. Conclusions: Safety/tolerability and efficacy findings in this small subgroup of older patients treated with adjunctive BRV are consistent with those observed in the much larger overall pooled population. BRV may be a suitable adjunctive treatment for older patients with uncontrolled focal seizures. Further larger studies in this population are warranted

Epilepsy and learning disabilities—a challenge for the next millennium?

AbstractPeople with learning disabilities often have seizures in addition to other disorders. Precise diagnosis may be difficult, but accuracy can be improved using electroencephalographic and video investigations. Following the establishment of a diagnosis of epilepsy, individually tailored care is necessary taking into account other health, behavioural and therapeutic issues. Neuroimaging may indicate a need for surgery which should not be automatically excluded as a treatment option. Rational antiepileptic drug use is advised, with emphasis upon the newer agents due to their better tolerance and ease of use. A programme of regular review will prevent over-medicating. Drug therapy may be withdrawn in a seizure-free patient. Realistic goals should be established for each individual coupled with an optimistic approach to care. However, future developments require a solid evidence base combined with rationality in all aspects of management. The community learning disability epilepsy nurse specialist is the key health-care professional who can ensure that a learning disabled individual with epilepsy is able to take full advantage of all available services. Education, closer collaboration and the mutual recognition of skills will ensure more cohesive and comprehensive care for this disadvantaged patient population

A Multiwavelength View at the Heart of the Superwind in NGC 253

Here we present new optical data from the Hubble Space Telescope of the NGC 253 central region, which reveal numerous discrete sources in a ring--like structure. This is combined with data at infrared, millimeter, radio and X-ray wavelengths to examine the nature of these discrete sources and the nucleus itself. We find that the majority of optical/IR/mm sources are young star clusters which trace out a ~50 pc ring, that defines the inner edge of a cold gas torus. This reservoir of cold gas has probably been created by gas inflow from a larger scale bar and deposited at the inner Lindblad resonance. The family of compact radio sources lie interior to the starburst ring, and in general do not have optical or IR counterparts. They are mostly SNRs. The radio nucleus, which is probably an AGN, lies near the centre of the ring. The X-ray emission from the nuclear source is extended in the ROSAT HRI detector indicating that not all of the X-ray emission can be associated with the AGN. The lack of X-ray variability and the flat radio spectrum of the nucleus, argues against an ultraluminous SN as the dominant energetic source at the galaxy core. The diffuse emission associated with the outflowing superwind is present in the central region on a size scale consistent with the idea of collimation by the gas torus.Comment: 26 pages, Latex, 6 figures, 4 tables, submitted to MNRA

Black-hole-regulated star formation in massive galaxies

Super-massive black holes, with masses larger than a million times that of the Sun, appear to inhabit the centers of all massive galaxies. Cosmologically-motivated theories of galaxy formation need feedback from these super-massive black holes to regulate star formation. In the absence of such feedback, state-of-the-art numerical simulations dramatically fail to reproduce the number density and properties of massive galaxies in the local Universe. However, there is no observational evidence of this strongly coupled co-evolution between super-massive black holes and star formation, impeding our understanding of baryonic processes within galaxies. Here we show that the star formation histories (SFHs) of nearby massive galaxies, as measured from their integrated optical spectra, depend on the mass of the central super-massive black hole. Our results suggest that black hole mass growth scales with gas cooling rate in the early Universe. The subsequent quenching of star formation takes place earlier and more efficiently in galaxies hosting more massive central black holes. The observed relation between black hole mass and star formation efficiency applies to all generations of stars formed throughout a galaxy's life, revealing a continuous interplay between black hole activity and baryon cooling.Comment: Published in Nature, 1 January 201

Hubble Space Telescope survey of the Perseus Cluster -IV: Compact stellar systems in the Perseus Cluster core and Ultra Compact Dwarf formation in star forming filaments

We present the results of the first search for Ultra Compact Dwarfs (UCDs) in the Perseus Cluster core, including the region of the cluster around the unusual Brightest Cluster Galaxy (BCG) NGC 1275. Utilising Hubble Space Telescope Advanced Camera for Surveys imaging, we identify a sample of 84 UCD candidates with half-light radii 10 pc < r_e < 57 pc out to a distance of 250 kpc from the cluster centre, covering a total survey area of ~70 armin^2. All UCDs in Perseus lie in the same size-luminosity locus seen for confirmed UCDs in other regions of the local Universe. The majority of UCDs are brighter than M_R = -10.5, and lie on an extrapolation of the red sequence followed by the Perseus Cluster dwarf elliptical population to fainter magnitudes. However, three UCD candidates in the vicinity of NGC 1275 are very blue, with colours (B-R)_0 < 0.6 implying a cessation of star formation within the past 100 Myr. Furthermore, large blue star clusters embedded in the star forming filaments are highly indicative that both proto-globular clusters (GCs) and proto-UCDs are actively forming at the present day in Perseus. We therefore suggest star forming filaments as a formation site for some UCDs, with searches necessary in other low redshift analogues of NGC 1275 necessary to test this hypothesis. We also suggest that tidal disruption of dwarf galaxies is another formation channel for UCD formation in the core of Perseus as tidal disruption is ongoing in this region as evidenced by shells around NGC 1275. Finally, UCDs may simply be massive GCs based on strong similarities in the colour trends of the two populations.Comment: 18 pages, 20 figures, 3 tables. Accepted for publication in MNRA

Spatially Resolved Stellar Spectroscopy of the Ultra-diffuse Galaxy Dragonfly 44. III. Evidence for an Unexpected Star-Formation History

We use the Keck Cosmic Web Imager integral-field unit spectrograph to: 1) measure the global stellar population parameters for the ultra-diffuse galaxy (UDG) Dragonfly 44 (DF44) to much higher precision than previously possible for any UDG, and 2) for the first time measure spatially-resolved stellar population parameters of a UDG. We find that DF44 falls below the mass--metallicity relation established by canonical dwarf galaxies both in and beyond the Local Group. We measure a flat radial age gradient ($m_{\rm age} \sim +0.01_{-0.08}^{+0.07}$ log Gyr kpc$^{-1}$) and a flat-to-positive metallicity gradient ($m_{\rm [Fe/H]} \sim +0.08_{-0.11}^{+0.11}$ dex kpc$^{-1}$), which are inconsistent with the gradients measured in similarly pressure-supported dwarf galaxies. We also measure a flat-to-negative [Mg/Fe] gradient ($m_{\rm [Mg/Fe]} \sim -0.18_{-0.17}^{+0.17}$ dex kpc$^{-1}$) such that the central $1.5$ kpc of DF44 has stellar population parameters comparable to metal-poor globular clusters. Overall, DF44 does not have internal properties similar to other dwarf galaxies and is inconsistent with it having been puffed up through a prolonged, bursty star-formation history, as suggested by some simulations. Rather, the evidence indicates that DF44 experienced an intense epoch of "inside-out" star formation and then quenched early and catastrophically, such that star-formation was cut off more quickly than in canonical dwarf galaxies.Comment: Accepted to Ap

Brane inflation and the WMAP data: a Bayesian analysis

The Wilkinson Microwave Anisotropy Probe (WMAP) constraints on string inspired ''brane inflation'' are investigated. Here, the inflaton field is interpreted as the distance between two branes placed in a flux-enriched background geometry and has a Dirac-Born-Infeld (DBI) kinetic term. Our method relies on an exact numerical integration of the inflationary power spectra coupled to a Markov-Chain Monte-Carlo exploration of the parameter space. This analysis is valid for any perturbative value of the string coupling constant and of the string length, and includes a phenomenological modelling of the reheating era to describe the post-inflationary evolution. It is found that the data favour a scenario where inflation stops by violation of the slow-roll conditions well before brane annihilation, rather than by tachyonic instability. Concerning the background geometry, it is established that log(v) > -10 at 95% confidence level (CL), where "v" is the dimensionless ratio of the five-dimensional sub-manifold at the base of the six-dimensional warped conifold geometry to the volume of the unit five-sphere. The reheating energy scale remains poorly constrained, Treh > 20 GeV at 95% CL, for an extreme equation of state (wreh ~ -1/3) only. Assuming the string length is known, the favoured values of the string coupling and of the Ramond-Ramond total background charge appear to be correlated. Finally, the stochastic regime (without and with volume effects) is studied using a perturbative treatment of the Langevin equation. The validity of such an approximate scheme is discussed and shown to be too limited for a full characterisation of the quantum effects.Comment: 65 pages, 15 figures, uses iopart. Shortened version, updated references. Matches publication up to appendix B kept on the arXi

Still at Odds with Conventional Galaxy Evolution: The Star Formation History of Ultra-Diffuse Galaxy Dragonfly 44

We study the star formation history (SFH) of the ultra-diffuse galaxy (UDG) Dragonfly 44 (DF44) based on the simultaneous fit to near-ultraviolet to near-infrared photometry and high signal-to-noise optical spectroscopy. In fitting the observations we adopt an advanced physical model with a flexible SFH, and we discuss the results in the context of the degeneracies between stellar population parameters. Through reconstructing the mass-assembly history with a prior for extended star formation (akin to methods in the literature) we find that DF44 formed 90 per cent of its stellar mass by $z\sim 0.9$ ($\sim 7.2$ Gyr ago). In comparison, using a prior that prefers concentrated star formation (as informed by previous studies of DF44's stellar populations) suggests that DF44 formed as early as $z\sim 8$ ($\sim 12.9$ Gyr ago). Regardless of whether DF44 is old or very old, the SFHs imply early star formation and rapid quenching. This result, together with DF44's large size and evidence that it is on its first infall into the Coma cluster, challenges UDG formation scenarios from simulations that treat all UDGs as contiguous with the canonical dwarf population. While our results cannot confirm any particular formation scenario, we can conclude from this that DF44 experienced a rare quenching event.Comment: 25 pages, 15 figures. Accepted for publication in MNRA