Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Effects of a museum-based social-prescription intervention on quantitative measures of psychological wellbeing in older adults

Aims: To assess psychological wellbeing in a novel social prescription intervention for older adults called Museums on Prescription, and to explore the extent of change over time in six self-rated emotions (‘absorbed, ‘active’, ‘cheerful’, ‘encouraged’, ‘enlightened’ and ‘inspired’). Methods: Participants (n=115) aged 65-94 were referred to museum-based programmes comprising 10, weekly sessions, by healthcare and third sector organisations using inclusion criteria (e.g. socially isolated; able to give informed consent; not in employment; not regularly attending social or cultural activities) and exclusion criteria (e.g. unable to travel to the museum; unable to function in a group situation; unlikely to be able to attend all sessions; unable to take part in interviews and complete questionnaires). In a within-participants design, the Museum Wellbeing Measure for Older Adults (MWM-OA) was administered pre-post session at start- mid- and end-programme. Twelve programmes, facilitated by museum staff and volunteers, were conducted in seven museums in central London and across Kent. In addition to the quantitative measures, participants, carers where present, museum staff and researchers kept weekly diaries following guideline questions, and took part in end programme in-depth interviews. Results: Multivariate analyses of variance showed significant participant improvements in all six MWM-OA emotions, pre-post session at start- mid- and end-programme. Two emotions, ‘absorbed’ and ‘enlightened’, increased pre-post session disproportionately to the others; ‘cheerful’ attained the highest pre-post session scores whereas ‘active’ was consistently lowest. Conclusions: Museums can be instrumental in offering museum-based programmes for older adults to improve psychological wellbeing over time. Participants in the study experienced a sense of privilege, valued the opportunity to liaise with curators, visit parts of the museum closed to the public, and handle objects normally behind glass. Participants appreciated opportunities afforded by creative and co-productive activities to acquire learning and skills, and get to know new people in a different context

Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1

We investigate the evolution in the distribution of surface brightness, as a function of size, for elliptical and S0 galaxies in the two clusters RDCS J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging with the Advanced Camera for Surveys on the Hubble Space Telescope to determine these sizes and surface brightnesses. Using three different estimates of the surface brightnesses, we find that we reliably estimate the surface brightness for the galaxies in our sample with a scatter of < 0.2 mag and with systematic shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type morphologies in both clusters. For each cluster, we use a magnitude limit in a band which closely corresponds to the rest-frame B, to magnitude limit of M_B = -18.8 at z=0, and select only those galaxies within the color-magnitude sequence of the cluster or by using our spectroscopic redshifts. We measure evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15) z mag. Our statistical errors are dominated by the observed scatter in the size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no statistically significant evolution in this scatter, though an increase in the scatter could be expected. Overall, the pace of luminosity evolution we measure agrees with that of the Fundamental Plane of early-type galaxies, implying that the majority of massive early-type galaxies observed at z =~ 1 formed at high redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6 in colo

Visual ecology of aphids – a critical review on the role of colours in host finding

We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

Comparison of the HadGEM2 climate-chemistry model against in situ and SCIAMACHY atmospheric methane data

Wetlands are a major emission source of methane (CH₄) globally. In this study, we evaluate wetland emission estimates derived using the UK community land surface model (JULES, the Joint UK Land Earth Simulator) against atmospheric observations of methane, including, for the first time, total methane columns derived from the SCIAMACHY instrument on board the ENVISAT satellite. Two JULES wetland emission estimates are investigated: (a) from an offline run driven with Climatic Research Unit–National Centers for Environmental Prediction (CRU-NCEP) meteorological data and (b) from the same offline run in which the modelled wetland fractions are replaced with those derived from the Global Inundation Extent from Multi-Satellites (GIEMS) remote sensing product. The mean annual emission assumed for each inventory (181 Tg CH₄ per annum over the period 1999–2007) is in line with other recently published estimates. There are regional differences as the unconstrained JULES inventory gives significantly higher emissions in the Amazon (by ~36 Tg CH₄ yr¯¹) and lower emissions in other regions (by up to 10 Tg CH₄ yr¯¹) compared to the JULES estimates constrained with the GIEMS product. Using the UK Hadley Centre's Earth System model with atmospheric chemistry (HadGEM2), we evaluate these JULES wetland emissions against atmospheric observations of methane. We obtain improved agreement with the surface concentration measurements, especially at high northern latitudes, compared to previous HadGEM2 runs using the wetland emission data set of Fung et al. (1991). Although the modelled monthly atmospheric methane columns reproduce the large-scale patterns in the SCIAMACHY observations, they are biased low by 50 part per billion by volume (ppb). Replacing the HadGEM2 modelled concentrations above 300 hPa with HALOE–ACE assimilated TOMCAT output results in a significantly better agreement with the SCIAMACHY observations. The use of the GIEMS product to constrain the JULES-derived wetland fraction improves the representation of the wetland emissions in JULES and gives a good description of the seasonality observed at surface sites influenced by wetlands, especially at high latitudes. We find that the annual cycles observed in the SCIAMACHY measurements and at many of the surface sites influenced by non-wetland sources cannot be reproduced in these HadGEM2 runs. This suggests that the emissions over certain regions (e.g. India and China) are possibly too high and/or the monthly emission patterns for specific sectors are incorrect. The comparisons presented in this paper show that the performance of the JULES wetland scheme is comparable to that of other process-based land surface models. We identify areas for improvement in this and the atmospheric chemistry components of the HadGEM Earth System model. The Earth Observation data sets used here will be of continued value in future evaluations of JULES and the HadGEM family of models

Are old-old patients with major depression more likely to relapse than young-old patients during continuation treatment with escitalopram?

<p>Abstract</p> <p>Background</p> <p>Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This <it>post-hoc </it>analysis compared time to relapse for <it>young-old </it>patients (n = 197) to that for <it>old-old </it>patients (n = 108).</p> <p>Method</p> <p>Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (<it>old-old</it>) or 65-74 years of age (<it>young-old</it>), treated with escitalopram 10-20mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS).</p> <p>Results</p> <p>After open-label escitalopram treatment, a similar proportion of <it>young-old </it>patients (78%) and <it>old-old </it>patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo <it>versus </it>escitalopram (χ²-test, df = 1, χ²= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for <it>old-old </it>versus <it>young-old </it>(χ²-test, df = 1, χ²= 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of <it>young-old </it>patients and 58.3% of <it>old-old </it>patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ²-test, χ²= 1.669, df = 1, p = 0.196).</p> <p>Conclusions</p> <p><it>Young-old </it>and <it>old-old </it>patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.</p

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Comparison of face-to-face versus email guided self-help for binge eating: study protocol for a randomised controlled trial

Background Guided self-help is a recommended first-step treatment for bulimia nervosa, binge eating disorder and atypical variants of these disorders. Further research is needed to compare guided self-help that is delivered face-to-face versus via email. Methods/Design This clinical trial uses a randomised, controlled design to investigate the effectiveness of providing guided self-help either face-to-face or via e-mail, also using a delayed treatment control condition. At least 17 individuals are required per group, giving a minimum N of 51. Discussion Symptom outcomes will be assessed and estimates of cost-effectiveness made. Results are proposed to be disseminated locally and internationally (through submission to conferences and peer-reviewed journals), and will hopefully inform local service provision. The trial has been approved by an ethics review board and was registered with ClinicalTrials.gov NCT01832792 on 9 April 2013

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Police performance measurement: an annotated bibliography

This study provides information to assist those involved in performance measurement in police organisations. The strategies used to identify the literature are described. Thematic sections cover; general overviews; methodological issues; performance management in other industries; national, international and cross-national studies; frameworks (e.g. Compstat; the Balanced Scorecard); criticisms (particularly unintended consequences); crime-specific measures; practitioner guides; performance evaluation of individual staff; police department plans and evaluations; annotated bibliographies in related areas, and; other literature. Our discussion offers two conclusions: the measures best aligned with performance are typically more expensive, while most operational data should only provide contextual information; the philosophy of open governance should be pursued to promote transparency, accountability and communication to improve police performance