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Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3–30 days post-ischaemic stroke into a phase II randomized (1:1), double-blind, placebo-controlled trial. Subjects received dexamphetamine (5 mg initially, then 10 mg for 10 subsequent doses with 3- or 4-day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl–Meyer (FM)), and functional scales (Barthel index (BI) and modified Rankin score (mRS)). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 min after, the first two doses. Thirty-three subjects were recruited, aged 33–88 (mean 71) years, males 52%, 4–30 (median 15) days post stroke to inclusion. Sixteen patients were randomized to placebo and seventeen to amphetamine. Amphetamine did not improve motor function at 90 days; mean (s.d.) FM 37.6 (27.6) vs control 35.2 (27.8) ( P =0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate (HR), were 11.2 mm Hg ( P =0.03), 9.5 mm Hg ( P =0.04) and 7 beats per minute ( P =0.02) higher, respectively, with amphetamine, compared with control. A nonsignificant reduction in myocardial perfusion (BUI) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and HR without altering cerebral haemodynamics.

Abstract Objective: To evaluate the primary care communications initiative, which introduced NHSnet to primary care in Scotland. Design: Semi-structured telephone interviews, postal questionnaire. Setting: All 15 Scottish health boards, random sample of 1 in 3 of all Scottish general practices. Participants: Information management and technology managers of health boards, 355 practice managers in the general practices. Main outcome measures: Variations between health boards in styles of project management, means of connection to NHSnet, costs to general practices, and training provided. Practices' levels of participation in initiative, initial use of NHSnet, and factors acting as incentives and disincentives to use of NHSnet. Results: 99% of Scottish general practices agreed to participate in initiative. Health boards varied significantly in project management styles (from minimal to total control), the nature of the networks they established (intranets or direct connections), costs to practices (from nothing to £125 per general practitioner per year), and training provided (from none to an extensive programme). In 56% of practices someone accessed NHSnet at least once a week. Practices varied considerably in amount of internet training received and staff groups targeted and in the intention to provide desktop access to NHSnet through a practice network. Conclusion: The initiative has successfully introduced a network that links Scottish general practices, health boards, and hospital trusts. However local variation in this “national” initiative may affect its use in primary care. Health authorities and general practices in England and Wales may wish to note these findings in order to avoid unhelpful variation.

Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01). Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy. Controlled-Trials.com ISRCTN83673558.

Capital punishment is not merely punishment; it is murder. It is murder legally permitted by those members of society who have never managed to outgrow primitive traits of bloody vengeance. It is neither morally nor rationally defensible. It is the pitifully weak and destructive answer of a defeated mankind who can think of no better solution to a...

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0–5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059). There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

The Northern Sub-Saharan African (NSSA) region, which accounts for 20%-25% of the global carbon emissions from biomass burning, also suffers from frequent drought episodes and other disruptions to the hydrological cycle whose adverse societal impacts have been widely reported during the last several decades. This paper presents a conceptual framework of the NSSA regional climate system components that may be linked to biomass burning, as well as detailed analyses of a variety of satellite data for 2001-2014 in conjunction with relevant model-assimilated variables. Satellite fire detections in NSSA show that the vast majority (>75%) occurs in the savanna and woody savanna land-cover types. Starting in the 2006-2007 burning season through the end of the analyzed data in 2014, peak burning activity showed a net decrease of 2-7%/yr in different parts of NSSA, especially in the savanna regions. However, fire distribution shows appreciable coincidence with land-cover change. Although there is variable mutual exchange of different land cover types, during 2003-2013, cropland increased at an estimated rate of 0.28%/yr of the total NSSA land area, with most of it (0.18%/yr) coming from savanna. During the last decade, conversion to croplands increased in some areas classified as forests and wetlands, posing a threat to these vital and vulnerable ecosystems. Seasonal peak burning is anti-correlated with annual water-cycle indicators such as precipitation, soil moisture, vegetation greenness, and evapotranspiration, except in humid West Africa (5°-10° latitude), where this anti-correlation occurs exclusively in the dry season and burning virtually stops when monthly mean precipitation reaches 4 mm d−1. These results provide observational evidence of changes in land-cover and hydrological variables that are consistent with feedbacks from biomass burning in NSSA, and encourage more synergistic modeling and observational studies that can elaborate this feedback mechanism.

The dicistrovirus Israeli Acute Paralysis Virus (IAPV) has been implicated in the worldwide decline of honey bees. Studies of IAPV and many other bee viruses in pure culture are restricted by available isolates and permissive cell culture. Here we show that coupling the IAPV major structural precursor protein ORF2 to its cognate 3C-like processing enzyme results in processing of the precursor to the individual structural proteins in a number of insect cell lines following expression by a recombinant baculovirus. The efficiency of expression is influenced by the level of IAPV 3C protein and moderation of its activity is required for optimal expression. The mature IAPV structural proteins assembled into empty capsids that migrated as particles on sucrose velocity gradients and showed typical dicistrovirus like morphology when examined by electron microscopy. Monoclonal antibodies raised to recombinant capsids were configured into a diagnostic test specific for the presence of IAPV. Recombinant capsids for each of the many bee viruses within the picornavirus family may provide virus specific reagents for the on-going investigation of the causes of honeybee loss.

Added genetic diversity among commercial maize (Zea mays L.) hybrids may further increase yields and safeguard against vulnerability. Introducing exotic germplasm into breeding programs would increase the genetic base from which elite commercial inbreds are derived. Ten populations of maize, created from Chinese and/or U.S. inbreds or strains, were evaluated by Griffing's diallel analysis for combining ability of grain yield, stalk lodging, ear height, flowering time, and European corn borer (ECB; Ostrinia nubilalis Hubner) resistance to estimate their potential as sources of exotic germplasm for U.S. breeding programs. Grain yield general combining ability was largest for the population Mo17 Syn.(H14)C5, a synthetic improved by half-sib selection using US13 as a tester. Grain yield specific combining ability was largest in the cross Chinese Mix 2 x Mo17 Syn.(H14)C5. Chinese Mix 2 x Mo17 Syn.(H14)C5 had more stalk lodging than the B73 x Mo17 and Pioneer Brand 3394 checks. Because of the high yield potential and other moderate-to-good agronomic traits of the cross combination, Chinese Mix 2 was selected as the best population for selection. Its large specific combining ability effect with Lancaster type material, which is commonly known in breeding programs, shows potential for further improvement. No native ECB resistance in Chinese germplasm was detected (two environments in 1 yr) compared with the resistant check Pioneer Brand 3184.