Neuropsychiatric features of Parkinson's disease in the era prior to the use of dopaminergic therapies

BACKGROUND: Psychosis in Parkinson's disease includes hallucinations and delusions. Other non-psychotic neuropsychiatric features include depression, anxiety and apathy. There is currently controversy over whether psychosis in Parkinson's is an intrinsic part of the disorder or the result of dopaminergic medications. This study aimed to examine a historical cohort of individuals with Parkinson's prior to the use of dopaminergic therapy to assess the prevalence of psychotic and other neuropsychiatric features. METHODS: The case notes of patients with Parkinson's disease admitted to the National Hospital for Neurology and Neurosurgery, London between 1924 and 1946 were examined. Demographic and clinical variables were extracted along with any neuropsychiatric features. Cases meeting criteria for encephalitis lethargica were excluded. RESULTS: 115 cases of individuals with Parkinson's disease were identified. 58 (41.7%) were female. Mean age was 54.0 (SD 9.6) years and mean time since Parkinson's diagnosis was 5.3 (SD 5.7) years. No individuals met criteria for encephalitis lethargica. No cases of hallucinations or delusions were reported. There was one case of an illusion in a patient who was using anticholinergic medication. Other neuropsychiatric features reported were sleep disorder (present in 10, 8.7%), depression (8, 7.0%), memory impairment (5, 4.3%), impulsivity (4, 3.5%), bradyphrenia (4, 3.5%), impaired attention (3, 2.6%), anxiety (1, 0.9%), fatigue (1, 0.9%) and apathy (1, 0.9%). CONCLUSIONS: Prior to the use of dopaminergic therapies, patients with Parkinson's disease admitted to hospital rarely, if ever, reported psychotic symptoms, although other neuropsychiatric symptoms were more prevalent. The main limitation is that a lack of systematic enquiry about psychotic symptoms may have resulted in underreporting

Realistic boundary conditions for stochastic simulations of reaction-diffusion processes

Many cellular and subcellular biological processes can be described in terms of diffusing and chemically reacting species (e.g. enzymes). Such reaction-diffusion processes can be mathematically modelled using either deterministic partial-differential equations or stochastic simulation algorithms. The latter provide a more detailed and precise picture, and several stochastic simulation algorithms have been proposed in recent years. Such models typically give the same description of the reaction-diffusion processes far from the boundary of the simulated domain, but the behaviour close to a reactive boundary (e.g. a membrane with receptors) is unfortunately model-dependent. In this paper, we study four different approaches to stochastic modelling of reaction-diffusion problems and show the correct choice of the boundary condition for each model. The reactive boundary is treated as partially reflective, which means that some molecules hitting the boundary are adsorbed (e.g. bound to the receptor) and some molecules are reflected. The probability that the molecule is adsorbed rather than reflected depends on the reactivity of the boundary (e.g. on the rate constant of the adsorbing chemical reaction and on the number of available receptors), and on the stochastic model used. This dependence is derived for each model.Comment: 24 pages, submitted to Physical Biolog

Observational Constraints on the Dependence of Radio-Quiet Quasar X-ray Emission on Black Hole Mass and Accretion Rate

In this work we use a sample of 318 radio-quiet quasars (RQQ) to investigate the dependence of the ratio of optical/UV flux to X-ray flux, alpha_ox, and the X-ray photon index, Gamma_X, on black hole mass, UV luminosity relative to Eddington, and X-ray luminosity relative to Eddington. Our sample is drawn from the SDSS, with X-ray data from ROSAT and Chandra, and optical data mostly from the SDSS; 153 of these sources have estimates of Gamma_X from Chandra. We estimate M_BH using standard estimates derived from the Hbeta, Mg II, and C IV broad emission lines. Our sample spans a broad range in black hole mass (10^6 < M_BH / M_Sun < 10^10) and redshift (z < 4.8). We find that alpha_ox increases with increasing M_BH and L_UV / L_Edd, and decreases with increasing L_X / L_Edd. In addition, we confirm the correlation seen in previous studies between Gamma_X and M_BH and both L_UV / L_Edd and L_X / L_Edd; however, we also find evidence that the dependence of Gamma_X of these quantities is not monotonic, changing sign at M_BH ~ 3 x 10^8 M_Sun. We argue that the alpha_ox correlations imply that the fraction of bolometric luminosity emitted by the accretion disk, as compared to the corona, increases with increasing accretion rate relative to Eddington. In addition, we argue that the Gamma_X trends are caused by a dependence of X-ray spectral index on accretion rate. We discuss our results within the context of accretion models with comptonizing corona, and discuss the implications of the alpha_ox correlations for quasar feedback. To date, this is the largest study of the dependence of RQQ X-ray parameters on black hole mass and related quantities, and the first to attempt to correct for the large statistical uncertainty in the broad line mass estimates.Comment: Accepted by ApJ, 23 pages, 15 figures, emulateapj styl

Pre-distortion adaptive optics for optical feeder links: simulations and performance analyses

Optical feeder links offer immense utility in meeting future communication demands—however, atmospheric turbulence limits their performance. This work targets this challenge through analyses of a bidirectional free-space optical communication (FSOC) link that incorporates pre-distortion adaptive optics (AO) between the next-generation optical ground station at the German Aerospace Center (DLR) Oberpfaffenhofen and the laser communications terminal on Alphasat—a satellite in geostationary orbit (GEO). The analyses are performed via end-to-end Monte Carlo simulations that provide realistic performance estimates of the bidirectional FSOC link for a GEO feeder link scenario. We find that applying pre-distortion AO reduces the total uplink losses of the bidirectional FSOC link by up to 10 dB and lessens the scintillation at the GEO satellite by an order of magnitude. Moreover, applying pre-distortion AO eases the link budget requirements needed for maintaining 99.9% link uptime by as much as 20-40 dB, while its use with a laser guide star shows an additional performance improvement of up to 8 dB. These findings demonstrate the desirability and feasibility of utilizing pre-distortion AO for the realization of optical feeder links

Insights into the influence of solvent polarity on the crystallization of poly(ethylene oxide) spin-coated thin films via in situ grazing incidence wide-angle X-ray scattering

Controlling polymer thin-film morphology and crystallinity is crucial for a wide range of applications, particularly in thin-film organic electronic devices. In this work, the crystallization behavior of a model polymer, poly(ethylene oxide) (PEO), during spin-coating is studied. PEO films were spun-cast from solvents possessing different polarities (chloroform, THF, and methanol) and probed via in situ grazing incidence wide-angle X-ray scattering. The crystallization behavior was found to follow the solvent polarity order (where chloroform chloroform > methanol). When spun-cast from nonpolar chloroform, crystallization largely followed Avrami kinetics, resulting in the formation of morphologies comprising large spherulites. PEO solutions cast from more polar solvents (THF and methanol) do not form well-defined highly crystalline morphologies and are largely amorphous with the presence of small crystalline regions. The difference in morphological development of PEO spun-cast from polar solvents is attributed to clustering phenomena that inhibit polymer crystallization. This work highlights the importance of considering individual components of polymer solubility, rather than simple total solubility, when designing processing routes for the generation of morphologies with optimum crystallinities or morphologies

What should be included in case report forms? Development and application of novel methods to inform surgical study design:a mixed methods case study in parastomal hernia prevention

OBJECTIVES: To describe the development and application of methods to optimise the design of case report forms (CRFs) for clinical studies evaluating surgical procedures, illustrated with an example of abdominal stoma formation. DESIGN: (1) Literature reviews, to identify reported variations in surgical components of stoma formation, were supplemented by (2) intraoperative qualitative research (observations, videos and interviews), to identify unreported variations used in practice to generate (3) a ‘long list’ of items, which were rationalised using (4) consensus methods, providing a pragmatic list of CRF items to be captured in the Cohort study to Investigate the Prevention of parastomal HERnias (CIPHER) study. SETTING: Two secondary care surgical centres in England. PARTICIPANTS: Patients undergoing stoma formation, surgeons undertaking stoma formation and stoma nurses. OUTCOME MEASURES: Successful identification of key CRF items to be captured in the CIPHER study. RESULTS: 59 data items relating to stoma formation were identified and categorised within six themes: (1) surgical approach to stoma formation; (2) trephine formation; (3) reinforcing the stoma trephine with mesh; (4) use of the stoma as a specimen extraction site; (5) closure of other wounds during the procedure; and (6) spouting the stoma. CONCLUSIONS: This study used multimodal data collection to understand and capture the technical variations in stoma formation and design bespoke CRFs for a multicentre cohort study. The CIPHER study will use the CRFs to examine associations between the technical variations in stoma formation and risks of developing a parastomal hernia. TRIAL REGISTRATION NUMBER: ISRCTN17573805

The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database

<p>Abstract</p> <p>Background</p> <p>Few studies have investigated factors associated with discontinuation of employment in patients with CFS/ME or quantified its impact on productivity.</p> <p>Methods</p> <p>We used patient-level data from five NHS CFS/ME services during the period 01/04/2006-31/03/2010 collated in the UK CFS/ME National Outcomes Database. We used logistic regression to identify factors associated with discontinuation of employment. We estimated UK-wide productivity costs using patient-level data on duration of illness before assessment by a CFS/ME service, duration of unemployment, age, sex and numbers of patients, in conjunction with Office for National Statistics income and population data.</p> <p>Results</p> <p>Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment "because of fatigue-related symptoms". Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors. Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness = 36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million.</p> <p>Conclusions</p> <p>CFS/ME incurs huge productivity costs amongst the small fraction of adults with CFS/ME who access specialist services.</p

New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3–2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition

Pre-distortion adaptive optics for optical feeder links: simulations and performance analyses

Optical feeder links offer immense utility in meeting future communication demands—however, atmospheric turbulence limits their performance. This work targets this challenge through analyses of a bidirectional free-space optical communication (FSOC) link that incorporates pre-distortion adaptive optics (AO) between the next-generation optical ground station at the German Aerospace Center (DLR) Oberpfaffenhofen and the laser communications terminal on Alphasat—a satellite in geostationary orbit (GEO). The analyses are performed via end-to-end Monte Carlo simulations that provide realistic performance estimates of the bidirectional FSOC link for a GEO feeder link scenario. We find that applying pre-distortion AO reduces the total uplink losses of the bidirectional FSOC link by up to 10 dB and lessens the scintillation at the GEO satellite by an order of magnitude. Moreover, applying pre-distortion AO eases the link budget requirements needed for maintaining 99.9% link uptime by as much as 20-40 dB, while its use with a laser guide star shows an additional performance improvement of up to 8 dB. These findings demonstrate the desirability and feasibility of utilizing pre-distortion AO for the realization of optical feeder links