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Quetiapine immediate release (quetiapine IR) improves PANSS total, positive, negative and general psychopathology scores in schizophrenia. This study (D1444C00132) evaluated the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) in patients with acute schizophrenia.
This was a 6-week, double-blind, randomised study (n=588) comparing quetiapine XR (400, 600 or 800 mg/day) and quetiapine IR (400 mg/day) with placebo. Efficacy was assessed using ANCOVA analyses of the change from baseline to study endpoint (Day 42) for: PANSS total score; positive, negative and general psychopathology subscale scores; and aggression and depression cluster scores (modified ITT population, LOCF). Changes in individual PANSS item scores were assessed post hoc.
At Day 42, there were statistically significant reductions (ie two-sided p-value <0.05) versus placebo with all doses of quetiapine XR for the change in PANSS total, positive, general psychopathology and aggression cluster scores. Changes in negative and depression cluster scores were statistically significant versus placebo for quetiapine XR 600 mg/day and 800 mg/day. There was statistically significant separation from placebo with quetiapine XR 600 mg/day and 800 mg/day for the change in 6/7 PANSS positive items, 5/7 negative items, and 12/16 general psychopathology items. For those items with no statistically significant separation from placebo, baseline scores were generally low.
Once-daily quetiapine XR is effective across a broad range of symptoms in acute schizophrenia, including positive and negative symptoms, as well as symptoms of general psychopathology, aggression and depression.
To evaluate efficacy and tolerability of quetiapine sustained release (SR) in a 6-week study (D1444C00132).
588 patients with acute schizophrenia (PANSS total ≥70; CGI-S ≥4) were randomised to fixed-dose quetiapine SR 400, 600 or 800 mg/day (once-daily), quetiapine immediate release (IR) 400 mg/day (200 mg twice-daily; 5-day dose-escalation schedule), or placebo. Quetiapine SR doses: 400, 600 mg reached by Day 2; 800 mg by Day 3. Primary endpoint: change from baseline to Day 42 in PANSS total score (LOCF; ANCOVA). Other assessments: PANSS response rate (% patients with ≥30% reduction in total score from baseline); CGI-I response rate (% patients with rating ≤3); CGI-S; AEs.
446 patients (76%) completed the study (similar across groups). LS mean change from baseline in PANSS total score at Day 42 showed significant improvement versus placebo (-18.8): -24.8 (p=0.03), -30.9 (p<0.001), and -31.3 (p<0.001), quetiapine SR 400, 600, and 800 mg, respectively; -26.6 (p=0.004), quetiapine IR. Statistical separation from placebo at Day 42 for: change from baseline in CGI-S (quetiapine SR 600 and 800 mg; IR); PANSS and CGI-I response rates (all active treatments). Most common AEs with quetiapine: somnolence and dizziness. There were no unexpected AEs with quetiapine SR. Incidence of EPS-related AEs was similar to placebo. Two quetiapine SR and two IR patients discontinued due to AEs in Week 1.
Once-daily quetiapine SR (400-800 mg) was effective versus placebo in patients with acute schizophrenia. Rapid dose escalation was well tolerated, with a therapeutically effective dose reached by Day 2.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
Background: Palliative care is a cornerstone of the management of progressive neurological illness, but there lacks a standardized evidence-based curriculum to teach the unique aspects of neurology-based palliative care to current learners. Methods: A needs assessment involving focus groups with patients, physicians, interdisciplinary members, and trainees was conducted to identify gaps in the current curriculum. The Kolb Learning Style Inventory identified learning strategies among neurology residents. A Palliative Medicine Comfort and Confidence Survey and knowledge pre-test was distributed to determine current learner needs. The curriculum was delivered during academic time, and feedback was obtained for further content revision. Results: Qualitative analysis was used to develop the curriculum with the key principles of symptom management, end-of life communication, psychosocial components of care, and community coordination. Learning styles varied, but preference for active experimentation and concrete experience was noted. Learners identified as comfortable with withdrawal of medical interventions, but requiring support on home palliative care referral, and management of terminal delirium and dyspnea. Further teaching was requested for end of life ethics and communication skills. Conclusions: By integrating current best evidence-based practice in palliative neurology with learner feedback, this project aims to create a comprehensive palliative care curriculum for neurology learners.
We present results from a multiwavelength study of the blazar PKS 1954–388 at radio, UV, X-ray, and gamma-ray energies. A RadioAstron observation at 1.66 GHz in June 2012 resulted in the detection of interferometric fringes on baselines of 6.2 Earth-diameters. This suggests a source frame brightness temperature of greater than 2 × 1012 K, well in excess of both equipartition and inverse Compton limits and implying the existence of Doppler boosting in the core. An 8.4-GHz TANAMI VLBI image, made less than a month after the RadioAstron observations, is consistent with a previously reported superluminal motion for a jet component. Flux density monitoring with the Australia Telescope Compact Array confirms previous evidence for long-term variability that increases with observing frequency. A search for more rapid variability revealed no evidence for significant day-scale flux density variation. The ATCA light-curve reveals a strong radio flare beginning in late 2013, which peaks higher, and earlier, at higher frequencies. Comparison with the Fermi gamma-ray light-curve indicates this followed ~ 9 months after the start of a prolonged gamma-ray high-state—a radio lag comparable to that seen in other blazars. The multiwavelength data are combined to derive a Spectral Energy Distribution, which is fitted by a one-zone synchrotron-self-Compton (SSC) model with the addition of external Compton (EC) emission.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Background: Graduating neurology residents require general palliative care skills. This study aims to develop an evidence-based palliative care curriculum to provide neurology residents with the general palliative care skills required for providing patient care along the continuum of life. Methods: A needs assessment of the palliative skills necessary for a neurology resident was performed. Focus groups were held with physicians, allied health care and senior residents. Semi-structured interviews were held with patients and their caregivers. Interviews analysed using qualitative thematic analysis techniques. The Kolb learning style inventory will determine the learning style of neurology residents and inform the curricular design. Results: Qualitative analysis identified 3 overarching challenges for neurology residents: 1) uncertainty regarding disease trajectory in neurology and timing of palliative care discussions; 2) cohesiveness of the health care team regarding end of life issues; 3) the role of the resident in initiating palliative care. Other principals identified for inclusion were: symptom management, communication, psychosocial aspects of care, care coordination and access, and myths and pitfalls in palliative care. Conclusions: This project will identify the current best evidence and expert opinion in palliative care neurology. The data will be used to develop a novel Canadian neurological palliative care curriculum.
The physical structure value of conserved grass/clover forages of spring harvest was evaluated by assessing effects of harvest time, conservation method, iNDF/NDF ratio and NDF intake (NDFI) per kg BW on chewing activity and fecal particle size in dairy heifers. A mixed sward consisting of ryegrass (Lolium perenne), red clover (Trifolium pratense) and white clover (Trifolium repens) was harvested in 2009 on May 9 (early) and 25 (late), and both cuts were conserved as silage and hay. The early silage, early hay, late silage and late hay contained dry matter (DM) of 454, 842, 250 and 828 g/kg, and NDF of 315, 436, 414 and 503 g/kg DM, respectively. Forages were fed as sole feed to four Jersey heifers of 435±30 kg BW in a 4×4 Latin square experiment. Feeding level was 90% of individual ad libitum intake, divided equally across two daily meals offered at 0800 and 1530 h. Chewing activity was estimated from recorded jaw movements (JM) oscillations continuously logged for 96 h and summarized per 24 h as mean effective rumination time and eating time. Eating behavior was further observed during four 20-min test meals. Weight proportion of large feces particles (>1.0 mm) and geometric mean fecal particle size (GPS) were calculated. Potentially indigestible NDF (iNDF) was estimated by incubation for 288 h in situ. The daily DM intake (DMI) decreased with progressing maturity at harvest (P<0.001) while daily NDFI was unaffected by harvest time (P>0.05). Earlier harvest led to less rumination per kg NDFI (P<0.01), similar eating time per kg NDFI (P>0.05) and similar proportion of large particles (P>0.01) compared with later harvest. Rumination time per kg NDFI decreased with higher NDFI per kg BW (P<0.001) and with lower iNDF/NDF ratio (P<0.01). Content and potential digestibility of NDF was greater in hay than in silage from the same harvest probably due to field loss and therefore confounded effects of conservation method. This study of high digestibility grass/clover silage and hay showed that NDF content and NDFI per kg BW affect fecal particle size and rumination time per kg NDF, and suggests implementation of NDFI per kg BW in systems evaluating physical structure in diets.
Relatively lower executive functioning is characteristic of individuals with schizophrenia. As low socio-economic status (SES) early in life (i.e. parent SES) has been linked with lower executive skills in healthy children, we hypothesized that parental SES (pSES) would be more strongly related to executive functioning in individuals with schizophrenia than in controls and have a greater impact on prefrontal cortical morphology.
Healthy controls (n = 125) and individuals with schizophrenia (n = 102) completed tests assessing executive functioning and intelligence. The groups were matched on pSES, which was evaluated with the Hollingshead–Redlich scale. A principal components analysis (PCA) was conducted on 10 variables from six executive tests, yielding three specific components (fluency, planning and response inhibition). Voxel-based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM) concentration.
Lower pSES was associated with lower scores across the three executive functioning components, and a significant group by pSES interaction was observed such that low pSES, in particular, affected individuals with schizophrenia. These effects remained significant when intellectual ability, education and self-SES (sSES) were added as covariates. VBM revealed that lower pSES was associated with reduced GM volume in several anterior brain regions, especially the superior frontal gyrus, in patients but not in controls.
These findings suggest that individuals with schizophrenia may be particularly vulnerable to the adverse impact of low pSES, in terms of both lower executive skills and reduced anterior GM volumes.
We report on follow-up observations of 20 short-duration gamma-ray bursts
(T90 < 2s) performed in
with the Gamma-Ray Burst Optical Near-Infrared Detector (GROND) between mid-2007 and the
end of 2010. This is the most homogeneous and comprehensive data set on GRB afterglow
observations of short bursts. In three cases, GROND was on target within less than 10 min
after the trigger, leading to the discovery of the afterglow of GRB 081226A and its faint
underlying host galaxy. In addition, GROND was able to image the optical afterglow and
follow the light curve evolution in five further cases: GRBs 090305, 090426, 090510,
090927, and 100117A. Three of the aforementioned six bursts with optical light curves show
a break: GRBs 090426 and 090510 as well as GRB 090305. For GRB 090927, no break is seen in
the optical/X-ray light curve until about 150 ks/600 ks after the burst. A decay slope of
the optical afterglow of GRB 100117A could be measured. Using these data supplemented by
about ten events taken from the literature, we compare the jet half-opening angles of long
and short bursts. We find a tentative evidence that short bursts have wider opening angles
than long bursts. However, the statistics are still very poor and follow-up observations
of these events are therefore very important to gain as much observational data as
The meeting was attended by 5 members of the WG (E. Bowell, G. Consolmagno, R. Courtain, R. Lopez, R. Schulz) one Task Group member (J. Watanabe), and several guests from the CSBN and CBAT. It was decided at the beginning of the meeting that the attending members of the WGPSN would discuss matters, provide their opinion or vote, and then ask the other 8 formal members to do the same via email. As a consequence the following discussed items have been agreed by majority vote of the WG members.
In the last decade, small and compact accelerator mass spectrometry (AMS) systems became available operating at terminal voltages of 1 MV and below. This new category of instruments has become competitive for radiocarbon detection to larger tandem accelerators and many of these instruments are successfully used for 14C dating or biomedical applications. The AMS group at ETH Zurich has demonstrated that small instruments can be built, which allow measurements also of other radionuclides such as 10Be, 26Al, 129I, and the actinides. 41Ca measurements can be performed with sufficient sensitivity for biomedical applications. A summary of recent developments made at the 500kV Pelletron in Zurich is given and its performance is compared with that of a commercial compact instrument from the company High Voltage Engineering Europe (HVEE) in Amersfoort, the Netherlands, operating at 1MV at CNA in Seville, Spain, as well as with that of larger AMS facilities. It turns out that the ion optics, stripper design, and the detection system are critical for the performance.
The Working Group on Planetary System Nomenclature (WG-PSN) develops, maintains and publishes guidelines for naming natural satellites of planets and surface features on all solar system bodies except Earth. When required the WG approves lists of new nomenclature, with accompanying explanatory notes, based on the established guidelines. Approved names are immediately added into the Gazetteer of Planetary Nomenclature. Objections based on significant, substantive problems may be submitted within a 3-months period, and will be ruled on by Division III.
A total of 701 comets received names between July 2005 and June 2008. Comets observed only from the SOHO and STEREO missions, as well as further comets recognized from the long-defunct SOLWIND satellite, accounted for 520 of these names.
The spatial and temporal changes in hydrology and pore water elemental and 87/86Sr compositions were used to determine contemporary weathering rates in a 65 to 226 ky old soil chronosequence formed from granitic sediments deposited on marine terraces along coastal California. Cl-corrected Na, K and Si increased with depth denoting inputs from the weathering of plagioclase and K-feldspar. Solute 87/86Sr exhibited progressive mixing of sea water-dominated precipitation with inputs from less radiogenic plagioclase. Linear approximations to these weathering gradients were used to determine plagioclase weathering rates of between 0.38 and 8.9x10-15 moles m-2 s-1. The lack of corresponding weathering gradients for Ca and Sr indicated short-term equilibrium with the clay ion exchange pool which requires periodic resetting by natural perturbations to maintain continuity, in spite of soil composition changes reflecting the effects of long-term weathering.