ORFEUS II and IUE Spectroscopy of EX Hydrae

Using ORFEUS-SPAS II FUV spectra, IUE UV spectra, and archival EUVE deep survey photometry, we present a detailed picture of the behavior of the magnetic cataclysmic variable EX Hydrae. Like HUT spectra of this source, the FUV and UV spectra reveal broad emission lines of He II, C II-IV, N III and V, O VI, Si III-IV, and Al III superposed on a continuum which is blue in the UV and nearly flat in the FUV. Like ORFEUS spectra of AM Her, the O VI doublet is resolved into broad and narrow emission components. Consistent with its behavior in the optical, the FUV and UV continuum flux densities, the FUV and UV broad emission line fluxes, and the radial velocity of the O VI broad emission component all vary on the spin phase of the white dwarf, with the maximum of the FUV and UV continuum and broad emission line flux light curves coincident with maximum blueshift of the broad O VI emission component. On the binary phase, the broad dip in the EUV light curve is accompanied by strong eclipses of the UV emission lines and by variations in both the flux and radial velocity of the O VI narrow emission component. The available data are consistent with the accretion funnel being the source of the FUV and UV continuum and the O VI broad emission component, and the white dwarf being the source of the O VI narrow emission component.Comment: 21 pages, 10 Postscript figures; LaTeX format, uses aaspp4.sty; table2.tex included separately because it must be printed sideways - see instructions in the file; accepted on 1999 Feb 20 for publication in The Astrophysical Journa

Therapeutic potential of transdermal glyceryl trinitrate in the management of acute stroke

The nitric oxide donor, glyceryl trinitrate (GTN), is a candidate treatment for the management of acute stroke with haemodynamic and potential reperfusion and neuroprotective effects. When administered as a transdermal patch during the acute and subacute phases after stroke, GTN was safe, lowered blood pressure, maintained cerebral blood flow, and did not induce cerebral steal or alter functional outcome. However, when given within 6 h of stroke onset, GTN reduced death and dependency (odds ratio 0.52; 95% confidence interval 0.34–0.78), death, disability, cognitive impairment and mood disturbance, and improved quality of life (data from two trials, n = 312). In a pooled analysis of four studies (n = 186), GTN reduced between-visit systolic blood pressure variability over days 1–7 compared with no GTN (mean difference -2.09; 95% confidence interval -3.83 to -0.35; p = 0.019). The efficacy of GTN given in the ultra-acute/pre-hospital setting is currently being assessed and, if found to be beneficial, the implications for hyperacute stroke practice are significant. Here, we discuss the evidence to date, potential mechanisms of action and future possibilities, including unanswered questions, for the therapeutic potential of GTN in acute stroke

Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

Background Human neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study. Methods We undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation. Findings Twenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures. Interpretation Administration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials. Funding ReNeuron, Innovate UK (application no 32074-222145). Trial registration number EudraCT Number: 2012-003482-1

Fall-Back Disks in Long and Short GRBs

We present numerical time-dependent calculations for fall-back disks relevant to GRBs in which the disk of material surrounding the black hole (BH) powering the GRB jet modulates the mass flow, and hence the strength of the jet. Given the initial existence of a small mass <10^{-4} msun near the progenitor with a circularization radius ~10^{10}-10^{11} cm, an unavoidable consequence will be the formation of an "external disk" whose outer edge continually moves to larger radii due to angular momentum transport and lack of a confining torque. For long GRBs, if the mass distribution in the initial fall-back disk traces the progenitor envelope, then a radius ~10^{11} cm gives a time scale ~10^4 s for the X-ray plateau. For late times t>10^7 s a steepening due to a cooling front in the disk may have observational support in GRB 060729. For short GRBs, one expects most of the mass initially to lie at small radii <10^8 cm; however the presence of even a trace amount ~10^{-9} msun of high angular momentum material can give a brief plateau in the light curve. By studying the plateaus in the X-ray decay of GRBs, which can last up to ~10^4 s after the prompt emission, Dainotti et al. find an apparent inverse relation between the X-ray luminosity at the end of the plateau and the duration of the plateau. We show that this relation may simply represent the fact that one is biased against detecting faint plateaus, and therefore preferentially sampling the more energetic GRBs. If, however, there were a standard reservoir in fall-back mass, our model can reproduce the inverse X-ray luminosity-duration relation. We emphasize that we do not address the very steep, initial decays immediately following the prompt emission, which have been modeled by Lindner et al. as fall-back of the progenitor core, and may entail the accretion of > 1 msun.Comment: 8 pages, 6 figures, to appear in the Astrophysical Journal, May 10, 2011, v. 73

Phase transitions in the Potts spin glass model

We have studied the Potts spin glass with 2-state Ising spins and s-state Potts variables using a cluster Monte Carlo dynamics. The model recovers the +- J Ising spin glass (SG) for s=1 and exhibits for all s a SG transition at T_{SG}(s) and a percolation transition at higher temperature T_p(s). We have shown that for all values of $s\neq 1$ at T_p(s) there is a thermodynamical transition in the universality class of a ferromagnetic s-state Potts model. The efficiency of the cluster dynamics is compared with that of standard spin flip dynamics.Comment: 8 pages, Latex, with 8 EPS fig

Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing. Trial registration ISRCTN8556238

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Is early center-based child care associated with tantrums and unmanageable behavior over time up to school entry?

Background. Existing research suggests that there is a relationship between greater exposure to center-based child care and child behavioral problems though the mechanism for the impact is unclear. However the measure used to document child care has usually been average hours, which may be particularly unreliable in the early months when fewer children are in center care. In addition individual trajectories for behavior difficulties have not been studied. Objective. The purpose of the current study was to examine whether the extent of exposure to center-based child care before two years predicted the trajectory of children’s difficult behavior (i.e., tantrums and unmanageable behavior) from 30 to 51 months controlling for child and maternal characteristics. Method. Data were drawn from UK-based Families, Children and Child Care (FCCC) study (n=1201). Individual growth models were fitted to test the relation between early center-based child care experiences and subsequent difficult behavior. Results. Children with more exposure to center-based care before two had less difficult behavior at 30 months, but more increase over time. Initial levels were predicted by higher difficult temperament and lower verbal ability. Higher difficult temperament and lower family socio-economic status predicted its change over time. Conclusion. Findings suggest that early exposure to center-based care before two years old is a risk factor for subsequent behavior problems especially when children have a longer period of exposure. A possible explanatory process is that child coping strategies to manage frustration are less well developed in a group context, especially when they lag behind in expressive language

The Potts Fully Frustrated model: Thermodynamics, percolation and dynamics in 2 dimensions

We consider a Potts model diluted by fully frustrated Ising spins. The model corresponds to a fully frustrated Potts model with variables having an integer absolute value and a sign. This model presents precursor phenomena of a glass transition in the high-temperature region. We show that the onset of these phenomena can be related to a thermodynamic transition. Furthermore this transition can be mapped onto a percolation transition. We numerically study the phase diagram in 2 dimensions (2D) for this model with frustration and {\em without} disorder and we compare it to the phase diagram of $i)$ the model with frustration {\em and} disorder and of $ii)$ the ferromagnetic model. Introducing a parameter that connects the three models, we generalize the exact expression of the ferromagnetic Potts transition temperature in 2D to the other cases. Finally, we estimate the dynamic critical exponents related to the Potts order parameter and to the energy.Comment: 10 pages, 10 figures, new result

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.