The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and ...presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
Secondary organic aerosol (SOA) and oxidized primary organic aerosol (OPOA) were produced in laboratory experiments from the oxidation of fourteen precursors representing atmospherically relevant ...biogenic and anthropogenic sources. The SOA and OPOA particles were generated via controlled exposure of precursors to OH radicals and/or O3 in a Potential Aerosol Mass (PAM) flow reactor over timescales equivalent to 1–20 days of atmospheric aging. Aerosol mass spectra of SOA and OPOA were measured with an Aerodyne aerosol mass spectrometer (AMS). The fraction of AMS signal at m/z = 43 and m/z = 44 (f43, f44), the hydrogen-to-carbon (H/C) ratio, and the oxygen-to-carbon (O/C) ratio of the SOA and OPOA were obtained, which are commonly used to characterize the level of oxidation of oxygenated organic aerosol (OOA). The results show that PAM-generated SOA and OPOA can reproduce and extend the observed f44–f43 composition beyond that of ambient OOA as measured by an AMS. Van Krevelen diagrams showing H/C ratio as a function of O/C ratio suggest an oxidation mechanism involving formation of carboxylic acids concurrent with fragmentation of carbon-carbon bonds. Cloud condensation nuclei (CCN) activity of PAM-generated SOA and OPOA was measured as a function of OH exposure and characterized as a function of O/C ratio. CCN activity of the SOA and OPOA, which was characterized in the form of the hygroscopicity parameter κorg, ranged from 8.4×10−4 to 0.28 over measured O/C ratios ranging from 0.05 to 1.42. This range of κorg and O/C ratio is significantly wider than has been previously obtained. To first order, the κorg-to-O/C relationship is well represented by a linear function of the form κorg = (0.18±0.04) ×O/C + 0.03, suggesting that a simple, semi-empirical parameterization of OOA hygroscopicity and oxidation level can be defined for use in chemistry and climate models.
Elemental compositions of organic aerosol (OA) particles provide useful constraints on OA sources, chemical evolution, and effects. The Aerodyne high-resolution time-of-flight aerosol mass ...spectrometer (HR-ToF-AMS) is widely used to measure OA elemental composition. This study evaluates AMS measurements of atomic oxygen-to-carbon (O : C), hydrogen-to-carbon (H : C), and organic mass-to-organic carbon (OM : OC) ratios, and of carbon oxidation state (OS C) for a vastly expanded laboratory data set of multifunctional oxidized OA standards. For the expanded standard data set, the method introduced by Aiken et al. (2008), which uses experimentally measured ion intensities at all ions to determine elemental ratios (referred to here as "Aiken-Explicit"), reproduces known O : C and H : C ratio values within 20% (average absolute value of relative errors) and 12%, respectively. The more commonly used method, which uses empirically estimated H2O+ and CO+ ion intensities to avoid gas phase air interferences at these ions (referred to here as "Aiken-Ambient"), reproduces O : C and H : C of multifunctional oxidized species within 28 and 14% of known values. The values from the latter method are systematically biased low, however, with larger biases observed for alcohols and simple diacids. A detailed examination of the H2O+, CO+, and CO2+ fragments in the high-resolution mass spectra of the standard compounds indicates that the Aiken-Ambient method underestimates the CO+ and especially H2O+ produced from many oxidized species. Combined AMS-vacuum ultraviolet (VUV) ionization measurements indicate that these ions are produced by dehydration and decarboxylation on the AMS vaporizer (usually operated at 600 degree C). Thermal decomposition is observed to be efficient at vaporizer temperatures down to 200 degree C. These results are used together to develop an "Improved-Ambient" elemental analysis method for AMS spectra measured in air. The Improved-Ambient method uses specific ion fragments as markers to correct for molecular functionality-dependent systematic biases and reproduces known O : C (H : C) ratios of individual oxidized standards within 28% (13%) of the known molecular values. The error in Improved-Ambient O : C (H : C) values is smaller for theoretical standard mixtures of the oxidized organic standards, which are more representative of the complex mix of species present in ambient OA. For ambient OA, the Improved-Ambient method produces O : C (H : C) values that are 27% (11%) larger than previously published Aiken-Ambient values; a corresponding increase of 9% is observed for OM : OC values. These results imply that ambient OA has a higher relative oxygen content than previously estimated. The OS C values calculated for ambient OA by the two methods agree well, however (average relative difference of 0.06 OS C units). This indicates that OS C is a more robust metric of oxidation than O : C, likely since OS C is not affected by hydration or dehydration, either in the atmosphere or during analysis.
We made new estimates of the Galactic escape speed at various Galactocentric radii using the latest data release of the RAdial Velocity Experiment (RAVE DR4). Compared to previous studies we have a ...database that is larger by a factor of 10, as well as reliable distance estimates for almost all stars. Our analysis is based on statistical analysis of a rigorously selected sample of 90 high-velocity halo stars from RAVE and a previously published data set. We calibrated and extensively tested our method using a suite of cosmological simulations of the formation of Milky Way-sized galaxies. Our best estimate of the local Galactic escape speed, which we define as the minimum speed required to reach three virial radii R340, is 533+54-41 km s-1 (90% confidence), with an additional 4% systematic uncertainty, where R340 is the Galactocentric radius encompassing a mean overdensity of 340 times the critical density for closure in the Universe. From the escape speed we further derived estimates of the mass of the Galaxy using a simple mass model with two options for the mass profile of the dark matter halo: an unaltered and an adiabatically contracted Navarro, Frenk & White (NFW) sphere. If we fix the local circular velocity, the latter profile yields a significantly higher mass than the uncontracted halo, but if we instead use the statistics for halo concentration parameters in large cosmological simulations as a constraint, we find very similar masses for both models. Our best estimate for M340, the mass interiorto R340 (dark matter and baryons), is 1.3+0.4-0.3 × 1012 M⊙ (corresponds to M200 = 1.6+0.5-0.4 × 1012 M⊙). This estimate is in good agreement with recently published, independent mass estimates based on the kinematics of more distant halo stars and the satellite galaxy Leo I.
In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia ...and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected. Next-of-kin provided consent for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur. All were skilled headers of the ball and had played football for an average of 26 years. Concussion rate was limited in six cases to one episode each during their careers. All cases developed progressive cognitive impairment with an average age at onset of 63.6 years and disease duration of 10 years. Neuropathological examination revealed septal abnormalities in all six post-mortem cases, supportive of a history of chronic repetitive head impacts. Four cases had pathologically confirmed CTE; concomitant pathologies included Alzheimer’s disease (
N
= 6), TDP-43 (
N
= 6), cerebral amyloid angiopathy (
N
= 5), hippocampal sclerosis (
N
= 2), corticobasal degeneration (
N
= 1), dementia with Lewy bodies (
N
= 1), and vascular pathology (
N
= 1); and all would have contributed synergistically to the clinical manifestations. The pathological diagnosis of CTE was established in four individuals according to the latest consensus diagnostic criteria. This finding is probably related to their past prolonged exposure to repetitive head impacts from head-to-player collisions and heading the ball thousands of time throughout their careers. Alzheimer’s disease and TDP-43 pathologies are common concomitant findings in CTE, both of which are increasingly considered as part of the CTE pathological entity in older individuals. Association football is the most popular sport in the world and the potential link between repetitive head impacts from playing football and CTE as indicated from our findings is of considerable public health interest. Clearly, a definitive link cannot be established in this clinico-pathological series, but our findings support the need for further systematic investigation, including large-scale case–control studies to identify at risk groups of footballers which will justify for the implementation of protective strategies.
We present the results of a coordinated campaign conducted with the Murchison Widefield Array (MWA) to shadow fast radio bursts (FRBs) detected by the Australian Square Kilometre Array Pathfinder ...(ASKAP) at 1.4 GHz, which resulted in simultaneous MWA observations of seven ASKAP FRBs. We de-dispersed the 24 × 1.28 MHz MWA images across the 170-200 MHz band taken at 0.5 s time resolution at the known dispersion measures (DMs) and arrival times of the bursts and searched both within the ASKAP error regions (typically ∼10′ × 10′), and beyond (4° × 4°). We identified no candidates exceeding a 5 threshold at these DMs in the dynamic spectra. These limits are inconsistent with the mean fluence scaling of = −1.8 0.3 ( , where is the observing frequency) that is reported for ASKAP events, most notably for the three high-fluence ( Jy ms) FRBs 171020, 180110, and 180324. Our limits show that pulse broadening alone cannot explain our non-detections, and that there must be a spectral turnover at frequencies above 200 MHz. We discuss and constrain parameters of three remaining plausible spectral break mechanisms: free-free absorption, intrinsic spectral turnover of the radiative processes, and magnification of signals at ASKAP frequencies by caustics or scintillation. If free-free absorption were the cause of the spectral turnover, we constrain the thickness of the absorbing medium in terms of the electron temperature, T, to <0.03 (T/104 K)−1.35 pc for FRB 171020.
Radio jets in NGC 4151: where eMERLIN meets HST Williams, D. R. A; McHardy, I. M; Baldi, R. D ...
Monthly notices of the Royal Astronomical Society,
12/2017, Letnik:
472, Številka:
4
Journal Article
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Abstract
We present high-sensitivity eMERLIN radio images of the Seyfert galaxy NGC 4151 at 1.51 GHz. We compare the new eMERLIN images to those from archival MERLIN observations in 1993 to determine ...the change in jet morphology in the 22 yr between observations. We report an increase by almost a factor of 2 in the peak flux density of the central core component, C4, thought to host the black hole, but a probable decrease in some other components, possibly due to adiabatic expansion. The core flux increase indicates an active galactic nucleus (AGN) that is currently active and feeding the jet. We detect no significant motion in 22 yr between C4 and the component C3, which is unresolved in the eMERLIN image. We present a spectral index image made within the 512 MHz band of the 1.51 GHz observations. The spectrum of the core, C4, is flatter than that of other components further out in the jet. We use HST emission-line images (H α, O iii and O ii) to study the connection between the jet and the emission-line region. Based on the changing emission-line ratios away from the core and comparison with the eMERLIN radio jet, we conclude that photoionization from the central AGN is responsible for the observed emission-line properties further than 4 arcsec (360 pc) from the core, C4. Within this region, a body of evidence (radio-line co-spatiality, low O iii/H α and estimated fast shocks) suggests additional ionization from the jet.
ABSTRACT We present broadband observations and spectral modeling of PKS B0008-421 and identify it as an extreme gigahertz-peaked spectrum (GPS) source. PKS B0008-421 is characterized by the steepest ...known spectral slope below the turnover, close to the theoretical limit of synchrotron self-absorption, and the smallest known spectral width of any GPS source. Spectral coverage of the source spans from 0.118 to 22 GHz, which includes data from the Murchison Widefield Array and the wide bandpass receivers on the Australia Telescope Compact Array. We have implemented a Bayesian inference model fitting routine to fit the data with internal free-free absorption (FFA), single- and double-component FFA in an external homogeneous medium, FFA in an external inhomogeneous medium, or single- and double-component synchrotron self-absorption models, all with and without a high-frequency exponential break. We find that without the inclusion of a high-frequency break these models cannot accurately fit the data, with significant deviations above and below the peak in the radio spectrum. The addition of a high-frequency break provides acceptable spectral fits for the inhomogeneous FFA and double-component synchrotron self-absorption models, with the inhomogeneous FFA model statistically favored. The requirement of a high-frequency spectral break implies that the source has ceased injecting fresh particles. Additional support for the inhomogeneous FFA model as being responsible for the turnover in the spectrum is given by the consistency between the physical parameters derived from the model fit and the implications of the exponential spectral break, such as the necessity of the source being surrounded by a dense ambient medium to maintain the peak frequency near the gigahertz region. This implies that PKS B0008-421 should display an internal H i column density greater than 1020 cm−2. The discovery of PKS B0008-421 suggests that the next generation of low radio frequency surveys could reveal a large population of GPS sources that have ceased activity, and that a portion of the ultra-steep-spectrum source population could be composed of these GPS sources in a relic phase.
We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to ...corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343–8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-β plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.
Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell ...survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
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