Global Entrepreneurship Monitor United Kingdom: 2007 Executive Report

This monitoring report compares Global Entrepreneurship Monitor (GEM) measures of entrepreneurial activity in the UK with participating G7 countries and the large industrialised or industrialising countries of Brazil, Russia, India and China ("BRIC"). It also summarises entrepreneurial activity within Government Office Regions of the UK

Abundance and evolution of galaxy clusters in cosmological models with massive neutrino

The time evolution of the number density of galaxy clusters and their mass and temperature functions are used to constrain cosmological parameters in the spatially flat dark matter models containing a fraction of hot particles (massive neutrino) additional to cold and baryonic matter. We test the modified MDM models with cosmic gravitational waves and show that they neither pass the cluster evolution test nor reproduce the observed height of the first acoustic peak in $\Delta T/T$ spectrum, and therefore should be ruled out. The models with a non-zero cosmological constant are in better agreement with observations. We estimate the free cosmological parameters in $\Lambda$MDM with a negligible abundance of gravitational waves, and find that within the parameter ranges $h\in (0.6, 0.7)$, $n\in (0.9, 1.1)$, (i) the value of $\Omega_\Lambda$ is strongly affected by a small fraction of hot dark matter, $f_\nu\equiv\Omega_\nu /\Omega_m\in (0, 0.2)$: $0.45 <\Omega_\Lambda <0.7$ ($1\sigma$ CL), and (ii) the redshift evolution of galaxy clusters alone reveals the following explicit correlation between $\Omega_\Lambda$ and $f_\nu$: $\Omega_\Lambda +0.5f_\nu =0.65\pm 0.1$. The present accuracy of observational data allows only to bound the fraction of hot matter, $f_\nu\in (0, 0.2)$ (the number of massive neutrino species remains undelimited, $N_\nu =1, 2, 3$).Comment: 9 pages, 7 figures, submitted in A&

Simulation of calcium phosphate species in aqueous solution: force field derivation

A new force field has been derived for the aqueous calcium phosphate system that aims to reproduce the key thermodynamic properties of the system, including free energies of hydration of the ions and the solubility of the solid mineral phases. Interactions of three phosphate anions (PO43-, HPO42-, and H2PO4-) with water were calibrated through comparison with the results obtained from ab initio molecular dynamics using both GGA and hybrid density functional theory with dispersion corrections. In the solid state, the force field has been evaluated by benchmarking against experiment and other existing models and is shown to reproduce the structural and mechanical properties well, despite the primary focus being on thermodynamics. To validate the force field, the thermodynamics of ion pairing for calcium phosphate species in water has been computed and shown to be in excellent agreement with experimental data

Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia. Alzheimer's & Dementia

INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer’s disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid (“PPA-Squared”). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA

Symptom-based staging for logopenic variant primary progressive aphasia

Background and purpose Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. Methods An international lvPPA caregiver cohort was surveyed on symptom development under an ‘exploratory’ survey (34 UK caregivers). Feedback from this survey informed the development of a ‘consolidation’ survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. Results Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. ‘Milestone’ symptoms were identified that anticipate daily-life functional transitions and care needs. Conclusions This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum

Ab Initio Calculation of the Lattice Distortions induced by Substitutional Ag- and Cu- Impurities in Alkali Halide Crystals

An ab initio study of the doping of alkali halide crystals (AX: A = Li, Na, K, Rb; X = F, Cl, Br, I) by ns2 anions (Ag- and Cu-) is presented. Large active clusters with 179 ions embedded in the surrounding crystalline lattice are considered in order to describe properly the lattice relaxation induced by the introduction of substitutional impurities. In all the cases considered, the lattice distortions imply the concerted movement of several shells of neighbors. The shell displacements are smaller for the smaller anion Cu-, as expected. The study of the family of rock-salt alkali halides (excepting CsF) allows us to extract trends that might be useful at a predictive level in the study of other impurity systems. Those trends are presented and discussed in terms of simple geometric arguments.Comment: LaTeX file. 8 pages, 3 EPS pictures. New version contains calculations of the energy of formation of the defects with model clusters of different size

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

From McKinlay, C. J. D., Alsweiler, J. M., Ansell, J. M., Anstice, N. S., Chase, J. G., Gamble, G. D., … Harding, J. E. (2015). Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. New England Journal of Medicine, 373(16), 1507–1518. https://doi.org/10.1056/NEJMoa1504909 Copyright © 2015 Massachusetts Medical Society. Reprinted with permission.Neonatal hypoglycemia is a common and readily treatable risk factor for neurologic impairment in children. Although associations between prolonged symptomatic neonatal hypoglycemia and brain injury are well established,1 the effect of milder hypoglycemia on neurologic development is uncertain.2 Consequently, large numbers of newborns are screened and treated for low blood glucose concentrations, which involves heel-stick blood tests, substantial costs, and the possibility of iatrogenic harm. Under current guidelines,3 up to 30% of neonates are considered to be at risk for hypoglycemia, 15% receive a diagnosis of hypoglycemia, and approximately 10% require admission to a neonatal intensive care unit,4 costing an estimated $2.1 billion annually in the United States alone.5 Associated formula feeding and possible separation of mother and baby reduce breast-feeding rates,6 with potentially adverse effects on broader infant health and development. In addition, pain-induced stress in neonates, such as repeated heel sticks, may itself impair brain development.7 Thus, to determine appropriate glycemic thresholds for treatment, there have been repeated calls for studies of the effect of neonatal hypoglycemia on long-term development.2,8 We report the results of the Children with Hypoglycaemia and Their Later Development (CHYLD) study, a large prospective cohort study of term and late-preterm neonates born at risk for hypoglycemia. The study investigated the relation between the duration, frequency, and severity of low glucose concentrations in the neonatal period and neuropsychological development at 2 years.Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069622), the Health Research Council of New Zealand (10-399), and the Auckland Medical Research Foundation (1110009)

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed

Global motion perception is associated with motor function in 2-year-old children

The final publication is available at Elsevier via https://doi.org/10.1016/j.neulet.2017.08.062 © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The dorsal visual processing stream that includes V1, motion sensitive area V5 and the posterior parietal lobe, supports visually guided motor function. Two recent studies have reported associations between global motion perception, a behavioural measure of processing in V5, and motor function in pre-school and school aged children. This indicates a relationship between visual and motor development and also supports the use of global motion perception to assess overall dorsal stream function in studies of human neurodevelopment. We investigated whether associations between vision and motor function were present at 2 years of age, a substantially earlier stage of development. The Bayley III test of Infant and Toddler Development and measures of vision including visual acuity (Cardiff Acuity Cards), stereopsis (Lang stereotest) and global motion perception were attempted in 404 2-year-old children (±4 weeks). Global motion perception (quantified as a motion coherence threshold) was assessed by observing optokinetic nystagmus in response to random dot kinematograms of varying coherence. Linear regression revealed that global motion perception was modestly, but statistically significantly associated with Bayley III composite motor (r2 = 0.06, P < 0.001, n = 375) and gross motor scores (r2 = 0.06, p < 0.001, n = 375). The associations remained significant when language score was included in the regression model. In addition, when language score was included in the model, stereopsis was significantly associated with composite motor and fine motor scores, but unaided visual acuity was not statistically significantly associated with any of the motor scores. These results demonstrate that global motion perception and binocular vision are associated with motor function at an early stage of development. Global motion perception can be used as a partial measure of dorsal stream function from early childhood.Eunice Kennedy Shriver National Institute of Child Health Human Development of the National Institutes of Health || award number R01HD0692201 Auckland Medical Research Foundation

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release