Thrombolysis in very elderly people: controlled comparison of SITS international stroke thrombolysis registry and virtual international stroke trials archive

<p>Objective To assess effect of age on response to alteplase in acute ischaemic stroke.</p> <p>Design Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.</p> <p>Setting Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).</p> <p>Participants 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 (“elderly,” mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity.</p> <p>Main outcome measures Functional outcomes at 90 days measured by score on modified Rankin scale.</p> <p>Results Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.</p> <p>Conclusions Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.</p&gt

Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial

<p><b>Background and Purpose:</b> NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings.</p> <p><b>Methods:</b> We randomized 1722 patients with acute ischemic stroke to a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours of stroke onset. The primary outcome was disability at 90 days, as measured by the modified Rankin Scale (mRS), a 6-point scale ranging from 0 (no residual symptoms) to 5 (bed-bound, requiring constant care). Additional and exploratory analyses included mRS at 7 and 30 days; subgroup interactions with final mRS; assessments of activities of daily living by Barthel index; and National Institutes of Health Stroke Scale (NIHSS) neurological scores at 7 and 90 days.</p> <p><b>Results:</b> NXY-059 significantly improved the distribution of the mRS disability score compared with placebo at 7, 30, and 90 days (Cochran-Mantel-Haenszel test P=0.002, 0.004, 0.038, respectively; 90-day common odds ratio 1.20; 95% CI, 1.01 to 1.42). The benefit was not attributable to any specific baseline characteristic, stratification variable or subgroup interaction. Neurological scores were improved at 7 days (odds ratio [OR], 1.46; 95% CI, 1.13, 1.89; P=0.003) and the Barthel index was improved at 7 and 30 days (OR, 1.55; 95% CI, 1.22, 1.98; P<0.0001; OR, 1.27; 95% CI, 1.01, 1.59; P=0.02).</p> <p><b>Conclusions:</b> NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. Benefit on neurological scores and activities of daily living was detectable early but not significant at 90 days; however, our trial was underpowered to measure effects on the neurological examination. The benefit on disability is not confounded by interactions and is supported by other outcome measures.</p&gt

Evidence for global cooling in the Late Cretaceous.

The Late Cretaceous ‘greenhouse’ world witnessed a transition from one of the warmest climates of the past 140 million years to cooler conditions, yet still without significant continental ice. Low-latitude sea surface temperature (SST) records are a vital piece of evidence required to unravel the cause of Late Cretaceous cooling, but high-quality data remain illusive. Here, using an organic geochemical palaeothermometer (TEX86), we present a record of SSTs for the Campanian–Maastrichtian interval (~83–66¿Ma) from hemipelagic sediments deposited on the western North Atlantic shelf. Our record reveals that the North Atlantic at 35¿°N was relatively warm in the earliest Campanian, with maximum SSTs of ~35¿°C, but experienced significant cooling (~7¿°C) after this to <~28¿°C during the Maastrichtian. The overall stratigraphic trend is remarkably similar to records of high-latitude SSTs and bottom-water temperatures, suggesting that the cooling pattern was global rather than regional and, therefore, driven predominantly by declining atmospheric pCO2 levels

Anisotropic low field behavior and the observation of flux jumps in CeCoIn5

The magnetic behavior of the heavy fermion superconductor CeCoIn5 has been investigated. The low field magnetization data show flux jumps in the mixed state of the superconducting phase in a restricted range of temperature. These flux jumps begin to disappear below 1.7 K, and are completely absent at 1.5 K. The magnetization loops are asymmetric, suggesting that surface and geometrical factors dominate the pinning in this system. The lower critical field (Hc1), obtained from the magnetization data, shows a linear temperature dependence and is anisotropic. The calculated penetration depth is also anisotropic, which is consistent with the observation of an anisotropic superconducting gap in CeCoIn5. The critical currents, determined from the high field isothermal magnetization loops, are comparatively low (around 4000 A/cm2 at 1.6 K and 5 kOe).Comment: 4 pages 3 figure

The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease

A novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50–400 nA currents in response to 100 μM L-glutamate. Responses to L-glutamate were concentration-dependent (pEC50 3.64 ± 0.11). Ibotenate was a partial agonist on IscaGluCl1. We detected no response to 100 μM aspartate, quisqualate, kainate, AMPA or NMDA. Ivermectin at 1 μM activated IscaGluCl1, whereas picrotoxinin (pIC50 6.20 ± 0.04) and the phenylpyrazole fipronil (pIC50 6.90 ± 0.04) showed concentration-dependent block of the L-glutamate response. The indole alkaloid okaramine B, isolated from fermentation products of Penicillium simplicissimum (strain AK40) grown on okara pulp, activated IscaGluCl1 in a concentration-dependent manner (pEC50 5.43 ± 0.43) and may serve as a candidate lead compound for the development of new acaricides

Evaluation of the protection against norovirus afforded by E. coli monitoring of shellfish production areas under EU regulations

EC Regulation 854/2004 requires the classification of bivalve mollusc harvesting areas according to the faecal pollution status of sites. It has been reported that determination of Escherichia coli in bivalve shellfish is a poor predictor of norovirus (NoV) contamination in individual samples. We explore the correlation of shellfish E. coli data with norovirus presence using data from studies across 88 UK sites (1,184 paired samples). We investigate whether current E. coli legislative standards could be refined to reduce NoV infection risk. A significant relationship between E. coli and NoV was found in the winter months (October to February) using data from sites with at least 10 data pairs (51 sites). We found that the ratio of arithmetic means (log10 E. coli to log10 NoV) at these sites ranged from 0.6 to 1.4. The lower ratios (towards 0.6) might typically indicate situations where the contribution from UV disinfected sewage discharges was more significant. Conversely, higher ratios (towards 1.4) might indicate a prevalence of animal sources of pollution; however, this relationship did not always hold true and so further work is required to fully elucidate the factors of relevance. Reducing the current class B maximum (allowed in 10% of samples) from 46,000 E. coli per 100 g (corresponding NoV value of 75750±103) to 18,000 E. coli per 100 g (corresponding NoV value of 29365±69) reduces maximum levels of NoV by a factor of 2.6 to 1; reducing the upper class B limit to 100% compliance with 4,600 E. coli per 100 g (corresponding NoV value of 7403±39) reduces maximum levels of NoV by a factor of 10.2 to 1. We found using the UK filtered winter dataset that a maximum of 200 NoV corresponded to a maximum of 128±7 E. coli per 100 g. A maximum of 1,000 NoV corresponded to a maximum of 631±14 E. coli per 100 g

Enantioselective organocatalytic synthesis of bicyclic resorcinols via an intramolecular Friedel-Crafts-type 1,4-addition: access to cannabidiol analogues

The organocatalytic transformation of resorcinols is extremely rare. In this article, we report a highly enantioselective, organocatalytic intramolecular cyclization of these systems by a Friedel–Crafts-type 1,4-addition using a Jørgensen-Hayashi-like organocatalyst with a large silyl protecting group, and show that heat improves reaction yield with virtually no detriment to enantioselectivity. A variety of bicyclic resorcinols were obtained with excellent enantioselectivities (up to 94%). To show the utility of these constructs, and as part of a wider project involving the synthesis of cannabinoid-like compounds, the resorcinol formed was used to generate both ‘normal’ and ‘abnormal’ cannabidiol (CBD) derivatives which were shown to have anticonvulsant activity

Lower limit on the neutralino mass in the general MSSM

We discuss constraints on SUSY models with non-unified gaugino masses and R_P conservation. We derive a lower bound on the neutralino mass combining the direct limits from LEP, the indirect limits from gmuon, bsgamma, Bsmumu and the relic density constraint from WMAP. The lightest neutralino (mneutralino=6GeV) is found in models with a light pseudoscalar with MA<200GeV and a large value for $tan\beta$. Models with heavy pseudoscalars lead to mneutralino>18(29)GeV for $\tan\beta=50(10)$. We show that even a very conservative bound from the muon anomalous magnetic moment can increase the lower bound on the neutralino mass in models with mu<0 and/or large values of $\tan\beta$. We then examine the potential of the Tevatron and the direct detection experiments to probe the SUSY models with the lightest neutralinos allowed in the context of light pseudoscalars with high $\tan\beta$. We also examine the potential of an e+e- collider of 500GeV to produce SUSY particles in all models with neutralinos lighter than the W. In contrast to the mSUGRA models, observation of at least one sparticle is not always guaranteed.Comment: 37 pages, LateX, 16 figures, paper with higher resolution figures available at http://wwwlapp.in2p3.fr/~boudjema/papers/bound-lsp/bound-lsp.htm

The Enthusiast’s Eye: The Value of Unsanctioned Knowledge in Design Historical Scholarship

If design history research relies solely on institutionalized documentation and academic scholarship – that is, sanctioned knowledge – not only will its purview be limited to a very narrow segment of design culture, it will also lose out on a vast array of sources to valuable knowledge about our material environment produced by amateurs, collectors, and enthusiasts – what we in this article define as “unsanctioned knowledge.” Because of its dissociation with professional institutions and academic protocols and their – albeit admittedly utopian, but nonetheless upheld – ideals of objectivity, this type of knowledge is typically considered fundamentally subjective in nature and therefore of little or no relevance and value to academic scholarship. In this article, we argue that, to the contrary, design historical scholarship has much to gain from engaging more seriously with the unsanctioned knowledge represented by the enthusiast's eye

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study

[Background and objective] We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS–International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies.[Methods] We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014–2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST.[Results] Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44–47), 46.0% (42–50), 38% (35–41) and 37% (35–41), respectively; death was 19.2% (19–21), 15.3% (12.7–18.4), 29.2% (27–32) and 28.6% (27–31); and SICH was 3.6% (3–4), 4.4% (3.0–6.4), 5.8% (4.7–7.1) and not available.[Conclusion] Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.SITS (Safe Implementation of Treatment in Stroke) is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, the Swedish Order of St. John, Friends of Karolinska Institutet and private donors, as well as from an unrestricted sponsorship from Boehringer Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, Ferrer International and EVER Pharma. SITS is currently conducting studies supported by Boehringer Ingelheim and Biogen, as well as in collaboration with Karolinska Institutet, supported by Stryker, Covidien and Phenox. N Ahmed is supported by grants provided by the Stockholm County Council and the Swedish Heart-Lung Foundation. S Holmin is supported by grants provided by the Söderberg Foundations, the Stockholm County Council, the Erling Persson Foundation, VINNOVA and HMT. Irene Escudero-Martínez has received a grant from ‘Fundación Progreso y Salud, Junta de Andalucía’ (grant EF-0437-2018). RM has been supported by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR). RH has been supported by the grants no. DRO–UHHK 00179906 from the Ministry of Health of the Czech Republic and no. PROGRES Q40 from Charles University, Czech Republic.Peer reviewe