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The treatment is very effective if started within three hours of stroke and definitely improves outcome if given up to 4. These results apply to a wide range of people with a wide range of severities of stroke and other medical conditions.

Acute ischaemic stroke is a major cause of death and disability worldwide. Most strokes are due to blockage of an artery in the brain by a blood clot ischaemic stroke e. Some are extracted from biological samples e. An overview of the literature on thrombolysis in acute ischaemic stroke in Wardlaw identified six randomised trials of various thrombolytic drugs including a total of just participants.

A Cochrane review published in Wardlaw updated the original review. It was updated again in participants in total Wardlaw , in participants Wardlaw b , in participants Wardlaw but even so, many essential questions remained unanswered: How big is the overall benefit? What is the latest time window in which the treatment is still beneficial?

Which grades of stroke severity and which types of stroke, as judged clinically and on brain imaging, are more likely to respond favourably to treatment? Should people aged over 80 years receive thrombolysis? Which types of patients are most likely to be harmed by treatment, and which to benefit from it e.

To answer these questions reliably, and in particular to be able to tailor treatment to the individual, more data are needed from new randomised controlled trials RCTs. Guidelines recommended that thrombolysis should be delivered by a clinical team with suitable training and experience and in a setting with appropriate facilities ESO Stroke Guidelines ; NICE Stroke Guideline A general review of the use of thrombolytic therapy in clinical practice and the clinical service required to deliver it was provided in a book on the management of stroke Warlow This updated review includes all trials completed and made public since , as well as additional data published since from trials included in earlier versions of the review.

The upper age limit of 80 years, stroke severity and new imaging data are also analysed. We wished to determine whether:. We sought to identify all truly randomised unconfounded trials of thrombolytic therapy compared with placebo or open control in people with acute ischaemic stroke. We included trials in which the exact method of randomisation was unknown, even after correspondence with the authors, if the available information suggested that the randomisation was not likely to be biased.

We included trials of participants with a definite acute ischaemic stroke CT or magnetic resonance MR scanning having excluded intracranial haemorrhage prior to randomisation. We excluded trials that were confounded by the treatment or control group receiving another active therapy which had not been factored in to the randomisation for example, thrombolytic drug plus another agent versus placebo, or thrombolytic drug versus another agent.

We considered all other outcomes as secondary. See the ‘Specialized register’ section in the Cochrane Stroke Group module. We searched for all trials in all languages using the following overlapping methods, and arranged translation of relevant papers published in languages other than English.

This review builds on a continuous data collection process that started in Two review authors JW, VM screened the records obtained from the electronic searches and excluded obviously irrelevant studies.

We sought additional unpublished information from the principal investigators of all the trials that appeared to meet our inclusion criteria. We resolved any disagreements by discussion.

The selection for update was verified by EB. Two review authors JM and VM checked the data extraction and resolved any discrepancies or uncertainties by discussion or clarification with the principal investigator. We assessed whether the method of randomisation would allow allocation concealment, the adequacy of efforts to blind treatment administration and outcome assessment.

For each included trial we collected information about:. We provide detailed ‘Risk of bias’ tables for the trial included since the last update. We extracted the number of participants in the treated and control groups who had:.

We also extracted data to perform subgroup analyses on time to treatment, age, stroke severity, prior or concomitant antithrombotic drug use, and attempted to find information on pretreatment brain imaging findings, blood pressure, and diabetes details below. Our definition of SICH included people who died or deteriorated clinically as a result of intracranial haemorrhage.

We have defined ‘early after the stroke’ as within the first seven to 10 days, as the trials each tended to use a slightly different time point, but all had collected information on intracranial haemorrhage certainly within the first 10 days.

Many symptomatic haemorrhages actually occurred within the first few days of the stroke. Thus the true number with SICH may be higher than that suggested by these data. On the other hand, heightened awareness of an association between haemorrhagic transformation and thrombolysis may mean that the investigators too readily attributed any neurological deterioration following treatment to intracranial haemorrhage, even if the amount of blood was small.

Therefore, it is also possible that the risk of intracranial haemorrhage has been overestimated Von Kummer Most parenchymatous haemorrhages were associated with symptoms, so we used the number of participants with parenchymatous haematoma as the number with symptomatic haemorrhages.

We contacted trial investigators to obtain all unpublished missing data where possible. Where data were still missing or had not been collected in the original trial, then that trial did not contribute to the relevant outcome. We clarified missing or unclear data with the principal investigator. The outcomes in two studies were very clearly described in the original texts and verification with the principal investigators was not necessary Haley ; Morris Heterogeneity might arise from a wide variety of factors, such as the design of the trials, the type of participants included, the use of concomitant treatments like aspirin or heparin, ancillary care during the acute treatment period or rehabilitation, lack of availability of certain data for a particular trial so that a trial appears as missing for a particular outcome, or simply by the play of chance, particularly in small trials Deeks ; Higgins We have endeavoured to include data from all trials on all prespecified outcomes, obtained from secondary publications or the trial investigators if unpublished.

We assessed the likelihood of missing trials using a funnel plot. We calculated absolute numbers of events avoided or caused per patients treated using the risk differences method provided in the Review Manager 5 software RevMan and also as the straight percentages calculated from the number of events per number randomised in the treated and control groups. However, please note that these events per treated data should be regarded with caution as they may produce misleading results, since the absolute risk amongst controls varies between trials.

We examined the effect of stroke severity, age under or over 80 years, time from stroke to treatment and the effect of having a large infarct on plain CT ASPECT score 7 or less on outcome after thrombolysis. We assessed the effect of time by several approaches: we examined the effect of time in all trials regardless of what time windows they contributed to, then in only those trials that contributed to all time windows, and then by latest time to randomisation. These approaches were used to maximise use of available data and minimise bias by excluding some trials from some analyses e.

We used the proportion who died in the control group to estimate the severity of stroke. We assessed:. We examined primarily the effect of the thrombolytic drug in all studies for all drugs combined. We assessed whether the effect of thrombolysis on functional outcome varied with the definition of dependency mRS 2 to 5, instead of 3 to 5.

We stratified trials by the proportion of participants given aspirin or heparin within the treatment period by time after stroke;. The search of the Cochrane Stroke Group Trials Register identified 19 potentially relevant new or ongoing trials, of which only one was completed and relevant IST3 The remainder of the publications were not relevant.

The search of MEDLINE and EMBASE identified references, which included many additional publications to trials that were already in the review, and several that were relevant to another review Wardlaw , but none that was relevant to this review.

This review includes all possible available information about all trials in an effort to provide as complete a record as possible of the available data on thrombolysis for acute ischaemic stroke. Reasons for these comments and further analyses are provided in the Clinical Reviews submitted by Genentech to the USA Food and Drug administration in support of the license application for alteplase www.

The trials performed in the s Abe ; Atarashi ; Ohtomo were methodologically different to the trials performed from the s onwards. The s trials used very low doses of thrombolytic drug, given daily intravenously for several days, and started up to five or 14 days after the stroke. However, it is possible to see in the figures what effect the exclusion of these early trials would have on the overall results.

As there was a significant adverse interaction between streptokinase and aspirin, which we felt was important to highlight, the data for the participants receiving streptokinase in the presence or absence of aspirin are presented separately that is, streptokinase versus control separate from streptokinase with aspirin versus aspirin.

The maximum time interval allowed between the onset of the stroke and the start of the treatment administration varied from within three hours to up to two weeks. Please note that the latter three trials Abe ; Atarashi ; Ohtomo do not contribute data to the analysis of early deaths or of death and dependency, as early deaths were not recorded and a functional outcome measure was not used in these trials. Data and outcomes of all included substances are reported for completeness.

Please note that trials testing lumbrokinase did not meet the inclusion criteria for this review. Ongoing trials are testing other new thrombolytic agents such as microplasmin or tenecteplase see Characteristics of studies awaiting classification and Characteristics of ongoing studies.

Antithrombotic use was not randomly assigned in any other trial and its permitted use varied:. Early outcome assessments were made at around seven to 10 days in most trials.

Some trials also performed more frequent assessments in the first few hours and days after the trial treatment. In this review, outcome events occurring within the first seven to 10 days whichever was the later date at which data were collected have been used to determine the effect of thrombolytic therapy on early outcome.

Please note that because of the difficulty of blinding the biological effect of thrombolytic therapy, it is important to ensure that outcome assessment is blinded and objective. Three trials Abe ; Atarashi ; Ohtomo used the ‘Global Improvement Rating’, which measures change in neurological status and safety outcome as a composite surrogate for functional outcome. There are differences in the primary outcome measure used between trials, in that some used a ‘poor functional outcome’ and some used a ‘good outcome’.

The ‘alive and favourable outcome’ mRS 0 to 1 and ordinal analysis were included in prespecified secondary outcome analyses. For most trials, it has been possible to obtain data on participants in each individual Rankin or Barthel group, or data dichotomised on Rankin 0 to 2 versus 3 to 6, or 0 to 1 versus 2 to 6, so that dependency in this review refers to Rankin, mRS or OHS 3 to 5 6 being dead unless otherwise stated.

We excluded two trials conducted prior to the availability of CT scanning Meyer ; Meyer as there was no way of confirming that the stroke was ischaemic. A further 73 trials have also been excluded due to a range of reasons given in the Characteristics of excluded studies table. Studies that were potentially relevant but were confounded are listed in the Characteristics of excluded studies table and the reason given. The concealment has successively improved over time with the development and utilisation of new randomisation methods, such as the use of a centralised computerised method with interactive interface for randomisation over the telephone or Internet.

In one of these trials IST3 a minimisation algorithm was used to balance the study arms for key prognostic variables like stroke severity before randomisation.

All participants in the study, irrespective of study phase, were blindly assessed by postal mail or telephone by a blinded and trained observer. However, it should also be noted that thrombolysis, due to its effects on the coagulation system at high doses, can be difficult to blind completely due to the obvious signs of bleeding prolonged bleeding at venepuncture sites, easy bruising, gingival or conjunctival haemorrhages, etc.

Furthermore, as thrombolytic agents are proteins, they froth when shaken in solution with water or saline, rather like egg white mixed with water and shaken. Thus, in addition to the possibilities for failure of treatment allocation concealment inherent in the randomisation methods used as outlined above, it is possible that treatment allocation could be guessed accurately by the physicians caring for the participant in the acute phase because of these biological effects.

All available data are included. More information is available for some trials than for others, either because the trial collaborators have published very actively on various aspects of their trial, or because in some cases further information is available from other sources for example, reports on NINDS appear on the US Food and Drug Administration FDA website as part of the licence application process.

We have avoided, as far as possible, any reporting bias by obtaining original data from the trial investigators where these have not been published. In any trials where there have been exclusions, these were made prior to the breaking of the randomisation code. For the earlier trials, with additional information from the principal investigators if necessary, we have attempted to find a final outcome for all randomised participants, rather than simply relying on the published data from which some randomised participants may have been excluded.

Another study AUST was discontinued on the basis of very slow recruitment after 24 participants of a planned sample of had been included. One study PROACT was stopped after completing two of its planned three dosage arms by the pharmaceutical provider. Examination of funnel plots for the main outcomes showed these to be symmetrical and therefore provided little evidence of publication bias.

See Data and analyses. The overall OR for all trials appears at the bottom of each plot. Also note that some outcomes have fewer trials contributing data than other outcomes. This is because not all trials collected data on all outcomes examined in this review, or if they did collect data on the particular outcome, it may not be available.

If data were available for a particular outcome, then the trial appears listed in the relevant analysis. That analysis is not repeated here. Data on deaths occurring within the first seven to 10 days were available for 13 trials participants; Analysis 1. There was a significant excess of early deaths with thrombolysis: Comparison 1 Any thrombolytic agent versus control, Outcome 1 Deaths from all causes within 7 to 10 days.

In the three trials using streptokinase, there was also a significant excess of early deaths OR 1. Data were available from 17 trials on fatal intracranial haemorrhage participants; Analysis 1. Comparison 1 Any thrombolytic agent versus control, Outcome 2 Fatal intracranial haemorrhage within 7 to 10 days. We calculated the effect of thrombolysis on death from causes other than fatal intracranial haemorrhage for the 10 trials that provided data on both early death and fatal intracranial haemorrhage participants; Analysis 1.

In comparison with Analysis 1. Comparison 1 Any thrombolytic agent versus control, Outcome 3 Deaths within the first 7 to 10 days from causes other than fatal intracranial haemorrhage.

Comparison 1 Any thrombolytic agent versus control, Outcome 4 Symptomatic including fatal intracranial haemorrhage within 7 to 10 days. Excluding the trials that used lower doses of thrombolysis and had lower rates of fatal and symptomatic intracranial haemorrhage had little effect on the overall result as they contributed relatively few of the data to this analysis.

There was no overall reduction in symptomatic infarct swelling with thrombolysis: This gave very similar results OR 0. Comparison 1 Any thrombolytic agent versus control, Outcome 5 Symptomatic including fatal cerebral oedema. Data were available for all 27 trials 10, participants Analysis 1.

Analysable data from 22 trials including all recently completed and large trials on functional outcome were available for participants Analysis 1. There was a significant reduction in death or dependency with thrombolysis: This gives an OR of 0. Death and dependency actually reflect two outcomes which may ‘pull’ in different directions.

Small studies may have more extreme results and give less reliable estimates of true treatment effect than large studies. If an alternative definition of ‘poor outcome’ Rankin score 2 to 6 is used in this analysis, and the analysis is restricted to just the 21 trials with both definitions available, then the ORs are as follows:. Comparison 1 Any thrombolytic agent versus control, Outcome 9 Death or dependency defined as mRS 2 to 6.

Comparison 1 Any thrombolytic agent versus control, Outcome 10 Death or dependency defined as mRS 3 to 6. Heterogeneity is present for poor outcome defined as mRS 2 to 6 as for poor outcome defined as mRS 3 to 6. Note that some individual trials ‘wobble’ from being positive to not positive in going between the mRS definitions some go one way and some the other but overall the trend is to more positive results with mRS 2 to 6.

We examined the effect of thrombolysis on dependency defined as mRS 3 to 5 in the 22 trials with analysable data participants; Analysis 1.

This would suggest that amongst those who avoid early death when most of the excess of deaths attributable to thrombolysis appear to occur , there is a highly significant and worthwhile reduction in the risk of being dependent with any thrombolytic treatment.

We provide data on the number of participants who were alive and independent mRS 0 to 2 Analysis 1. There are obviously many other possible causes of heterogeneity, but it has not been possible to examine these systematically at the present time. These include, for example, the availability of data, the design of the trials, other aspects of the participant population apart from stroke severity, and the play of chance amongst what are still mainly relatively small trials.

For example, the desmoteplase trials included participants as late as nine hours, whereas most other trials only included participants up to six hours. Any apparent differences between drugs may therefore be due to factors other than the drug in question. It is not possible to comment on the effect of aspirin use prior to the stroke; although some trials recorded prior aspirin use, we could not extract data from the publications in a comparable manner and none of the earlier trials balanced randomisation on prior aspirin use.

The actual cause of the increase in early and total deaths with streptokinase and aspirin appears largely to be due to cerebrovascular events. Aspirin with streptokinase significantly increased the number of deaths in hospital from all causes OR 2. There was no difference in deaths from neurological causes without intracranial haemorrhage, but note also that more participants in the streptokinase plus aspirin group died of neurological causes without a CT scan or autopsy, so could also have had an intracranial haemorrhage, that is, the increase in intracranial haemorrhage with aspirin and streptokinase may be even greater Ciccone Comparison 1 Any thrombolytic agent versus control, Outcome 14 Deaths from all causes ordered by antithrombotic drug use.

However, this crude comparison may mask an important relationship between stroke severity and hazard with thrombolysis. Also, unfortunately, analysis based on an outcome in the control group is prone to bias due to regression to the mean Sharp A first attempt has now been made in the IST3 trial. The participants with more severe stroke had at least the same benefit of thrombolytic treatment as those with less severe stroke.

Comparison 1 Any thrombolytic agent versus control, Outcome 15 Deaths from all causes ordered by stroke severity. There was a significant reduction in the number of dead or dependent participants allocated thrombolysis who were randomised within three hours Thus, heterogeneity present in the analysis of all trials, all time windows and drugs, is removed for participants randomised within three hours of stroke. Although there appeared to be more reduction in death or dependency in participants treated within three hours, the difference was not significant: three hours, OR 0.

Comparison 1 Any thrombolytic agent versus control, Outcome 17 Death or dependency by time to treatment up to 6 hours: all agents: only trials randomising in both 0 to 3 and 3 to 6 hour time windows.

This should not be interpreted to mean that time to treatment is unimportant, but rather that other factor s like stroke severity may have confounded the association between time and outcome, and cannot be corrected for in this tabular analysis.

This provided data at up to three hours, up to 4. There was surprisingly little difference in ORs for each time point: zero to three hours, OR 0.

Comparison 1 Any thrombolytic agent versus control, Outcome 20 Death or dependency by latest time to randomisation. An analysis of the effect of time on the proportion of participants who were alive and independent Analysis 1. Data on participants treated within three hours of stroke are available for 11 trials Analysis 1. To compare treatment within three hours with treatment between three and six hours, we performed a similar analysis to those above for death and dependency Analysis 1. Here there was a significant difference in treatment effect between those treated within three hours OR 1.

Comparison 1 Any thrombolytic agent versus control, Outcome 27 Death by latest time to treatment. We also compared the outcome SICH across all trials stratified by latest time to randomisation Analysis 1. There was surprisingly little difference in ORs for each time point: zero to three hours, OR 5.

Comparison 1 Any thrombolytic agent versus control, Outcome 30 Symptomatic intracranial haemorrhage by latest time to treatment. With treatment up to six hours, the effect of rtPA on reducing the proportion of participants who were dead or dependent aged over 80 years OR 0. For participants treated within three hours Analysis 1.

We restricted this analysis to just trials testing intravenous thrombolysis. Amongst participants selected on the basis of plain CT, Amongst participants selected on the basis of plain CT, 8. In all, participants provided data for this analysis. Amongst participants allocated to thrombolysis, This can be compared crudely with analysis of death or dependency for the combined intravenous thrombolysis trials which gave an OR of 0.

These are not direct comparisons, and there are many other differences between the trials apart from the route of administration; this analysis should therefore be regarded with extreme caution.

There is strong evidence from 27 trials in 10, participants on the immediate hazards and the apparent net benefit of thrombolytic therapy given up to within three hours of acute ischaemic stroke, with overall benefit suggested up to six hours, for people aged over or under 80 years, and with different stroke severities.

Most of the excess of deaths with thrombolysis occurred early and was explained by fatal intracranial haemorrhage. However, dependency was reduced in survivors so overall there was a significant net benefit.

For every people treated with thrombolysis, 41 avoided death or dependency. There was no clear increase in hazard ICH or death with increasing time up to six hours after stroke, although there was some evidence of decreasing benefit reduction in death and dependency. Therefore, increasing time to treatment may reduce benefit more than it increases the hazard of thrombolysis. There is now good data on the effect of thrombolytic therapy in the elderly, in whom stroke is most common.

People over 80 constitute a significant and increasing proportion of patients with stroke. The European license has an upper age limit of 80 years and has further strict selection criteria compared with the USA, where the license is based mainly on the NINDS trial and does not have an upper age limit.

Among other limitations in Europe, an upper limit of stroke severity has also been introduced, as has a contraindication in people with the combined occurrence of diabetes and previous stroke.

This indicates that more data are needed to provide more robust results. The need for more data from new trials is also supported by the fact that the data are relatively unstable.

The fact that a neutral trial can become positive, or vice versa, or heterogeneity can be apparently removed by such a small alteration in the endpoint analysed simply emphasises the instability of the data and also advocates for alternative more robust ways of analysing data.

The heterogeneity could have arisen from many sources, including differences in the design of the trials, in the type of participants included, in the availability of data to contribute to the present analysis not all trials contributed data to all outcome analyses , and in the fact that these can only be considered as small trials for a condition as heterogeneous as ischaemic stroke.

Individual data will be able to examine whether factors such as sex, blood glucose, etc. Comparisons of different thrombolysis drugs, doses and routes of administration are addressed in a separate Cochrane review Wardlaw Whether or not other, more advanced imaging modalities, such as CT perfusion or magnetic resonance MR diffusion with perfusion, would improve patient selection or allow an extension of time window to treatment is the subject of ongoing trials EXTEND.

The trials included in this review are small in comparison with the thrombolytic therapy in myocardial infarction trials. Nonetheless, this version of the review, with the addition of IST3 , includes a wider range of participants, with many more aged over 80 years, than previous versions.

This is an effect of the principal methodology of IST3 with the application of the uncertainty principle, which states that when there is a clear indication for treatment the person should be treated, and when there clearly is a contraindicated the person should not be treated; only where the tested treatment is promising but unproven could the participant be randomised.

This approach provides the chance to test wider treatment criteria. There are substantially more data with the inclusion of participants from IST3 However, not all trials contributed to all analyses, some analyses only include five or so trials and there were imbalances in stroke severity and age between treatment groups in some earlier trials.

There remains significant heterogeneity for some outcomes and lack of a complete picture of the sources of heterogeneity, meaning that there is scope for more trials. This is particularly the case for mild strokes. We have not been able to identify clear reasons why some people do poorly with thrombolysis. In contrast, the benefit of thrombolysis declines with time, fewer patients being alive and independent the later the treatment.

The time window beyond which there is unlikely to be any benefit or too much hazard with thrombolytic therapy is unclear. The modifiers of the adverse effects of thrombolytic mode of action remain undetermined.

There is a clear time dependency, with fewer participants treated within three hours of stroke being dead or dependent, than participants treated between three and six hours, but the latest time window remains undetermined. Other trials that tested other thrombolytic regimens beyond six hours suggest that the benefit may extend to nine hours or even longer in selected people. Although these trials were themselves not positive, when combined the overall result suggests that thrombolysis reduces death or dependency even at these later times.

Thus, the time window for benefit probably extends to, and even beyond, six hours in selected people. However, this should not encourage complacency about the need for speedy treatment in ischaemic stroke.

There is little information on which thrombolytic drug might have most benefit and least hazard, and there is little information on which dosage of drug has least hazard and most benefit Wardlaw Direct randomised comparisons would be required Dundar The Chinese UK trial Chen had two doses of urokinase, but was underpowered to detect any difference between them.

Note that further details on direct randomised comparisons of drug or dose are included in a separate Cochrane Review Wardlaw , for which there are few additional data since its original publication. This information is important for understanding the impact of thrombolytic treatment on health economics.

It is difficult to assess the cost effectiveness of thrombolytic treatment. One trial has a prospective substudy ongoing for the measured and modelled evaluation of cost effectiveness IST3 The concerns about quality in earlier trials are largely overcome.

This review is the result of an ongoing process involving the collaborative effort of many researchers worldwide and the principal investigators of many of the thrombolysis trials. At present, this review represents all of the evidence from the randomised controlled studies on the effects of thrombolytic therapy on acute ischaemic stroke.

Comparisons of trials using different thrombolytic drugs should be treated with caution as these comparisons are indirect; available data on direct comparisons are presented in the companion review Wardlaw We have tried to include all available tabular data and have checked the accuracy of it rigorously. We have tried not to miss any relevant completed trials. We can only apologise if we have overlooked some available data on an outcome in an included trial or have overlooked a trial completely.

The analyses based on tabular data in the present review are consistent with these individual patient data analyses. However, patient surveys are ultimately voluntary and therefore are inevitably prone to potential bias through incomplete data. In future trials it would be helpful if data could be collected in such a way as to be compatible with the simple and fundamental effect parameters used in this review e. This review The Cochrane Library Issue 1, states that “..

However, Haley et al published that “Intravenous heparin was prohibited until at least 30 minutes after the infusion was complete..

Wardlaw et al have tried to contact Haley et al but without success. Hence, they have changed the text to “.. In the Risk of bias in included studies section, it would be helpful: 1. And if missing data was imputed, how was it done, and was it done in a similar way in each trial? Also, presenting sensitivity analyses and including an available case analysis would be useful. This is an important risk of bias criterion not addressed in the review. In the Results section and subsequent discussions and conclusions: 1.

The ‘average’ of these two groupings does not represent the ‘whole’. Addressing the impact of risk of bias assessments could be important for results interpretation and discussion. The changes above could be applied relatively quickly and are important considering the Cochrane review could be expected to be the most valid, thorough and current systematic review for this subject.

We thank Brian Alper and colleagues for their interest in our review, and for their comments. Our responses in bold are listed below point by point. Many of the points raised cannot be answered by the tabular data of the review for example the effects in different time splits.

Response: Thank you for your interest in the review and for taking the time to submit this critique. Response: Thank you. We have provided ‘Risk of bias’ tables for the trials included since the last update, and plan to extend to all trials in the next revision.

However, we clearly state the major issues related to bias in the text and state in the Methods in ‘Assessment of risk of bias’:. There was more detail about each trial in the text in earlier versions and in drafts of the present version. However, space constraints imposed by the Cochrane Database of Systematic Reviews CDSR , the large volume of important information that now has to be included, and the historical nature of some of the trials which, note, are also relatively small , meant that these details have not been retained in the text.

Note we state clearly in Methods, ‘Dealing with missing data’:. The risk of bias from incomplete data is dependent on whether or not the trials used blinded outcome assessment. We will therefore also refer to Results, from the five sections on five different important sources of bias:.

Also, the risk of bias from incomplete data is dependent on other sources of bias. We have, therefore, copied from the three other sections on different important sources of bias in the Results section, here for avoidance of doubt:. Response: ‘Intention to treat’ means analysed by treatment group to which the subject was assigned at randomisation, rather than by the treatment that they actually got. This is a standard term. The data are as published in the individual trials in almost all cases and can be extracted should you wish to repeat these analyses yourselves.

In a few trials, additional unpublished data were sought and included but these were mostly for secondary outcomes. Also see above. Response: A detailed discussion on baseline imbalance was included in previous versions of this review over the last 15 years but has mostly been removed from the current version due mainly to space constraints and because there has been an extensive debate and reanalysis e. Also see sections on bias from Results copied above.

The several time subgroups are clearly labelled and their presence explained in the text. Response: See above. Please note a methodological point however: the lack of patients randomised beyond six hours means that it is not possible to determine the very latest time window at present — for now we can only be confident of some benefit out to 5 hours — a larger sample, as is seen where all thrombolytic drugs 10, patients are considered, suggests a definite benefit out to six hours.

Confirmation of this point will be possible with the results of more later time window trials. Note that the recent positive small thrombectomy trials had time windows out to 8 hours. Response: We have above copied from the five sections on different important sources of bias, from Results. For avoidance of doubt, please see also the three sections on these points in the Discussion:. Response: Thank you but please take note of the above points, particularly that of space constraints. A large amount of text had to be culled from the present version at a late stage.

Perhaps the CDSR could consider increasing their space — an electronic publishing medium should not impose text space constraints. Earlier versions provide detailed descriptions and discussion of baseline imbalance. Response: The STTC has already done exactly what you suggest and published both the protocol and the results in For the Cochrane review, all available data are in the data tables, and the primary and secondary trials publications are all listed in the review so that interested readers can go and replicate this 25 years’ worth of analysis should they wish.

We previously provided feedback dated March 21, and your many responses to numerous concerns did not address a highly specific concern regarding the baseline difference in history of prior stroke in ECASS III, and how adjusting for this may negate any evidence of efficacy for alteplase 3 to 4.

Detailed discussions on baseline imbalances that were included in previous versions of this review , , or do not adequately cover the baseline difference in history of prior stroke in ECASS III and its specific influence on conclusions regarding efficacy 3 to 4.

In the ECASS III report, the adjusted analyses to show the primary outcome was robust when adjusting for baseline differences did not adjust for the history of prior stroke. The P value for this baseline difference in history of stroke, a potentially confounding variable, was corrected online in from 0. Epub November 8. Thus, this specific key baseline difference appears to be the primary contributor to the “statistically significant benefit” reported in ECASS III and conclusions of efficacy derived from this data or any other data should require substantial transparency and scrutiny to be accepted.

Until such reanalysis is done, it is most prudent to acknowledge this specific risk of bias, recognize its potential effect on the overall body of evidence specific to use of alteplase 3 to 4.

We thank Dr Alpers and colleagues for their continuing interest in the review of thrombolysis in acute ischaemic stroke. We are sorry that our responses did not address one highly specific concern. You cite a letter by Shy published in the Journal of Emergency Medicine in support of this concern. Bluhmki et al [1] also performed a fully adjusted analysis including prior stroke, and also reported several additional outcomes and subgroup analyses beyond those provided in the original NEJM primary report [2].

This would suggest that the effect of prior stroke is unlikely to be sufficient to negate the positive result of ECASS 3 on mRS 0 to 1. The Cochrane Review has several sections on risk of bias focusing on the main messages that apply to multiple trials. For example, about half the trials had various baseline imbalances, which were inevitable as they did not use central randomisation with minimisation, and some were of similar size or worse than the prior stroke imbalance in ECASS 3 like those in NINDS.

We believe that these major messages are more relevant than to focus on only one trial. Indeed, Cochrane editorial policy means that the limited space precludes providing very detailed descriptions of all variables in all trials. Protocol first published: Issue 1, Review first published: Issue 1, Although supported in part by a grant from the NHS Executive, the opinions and views expressed in this update do not necessarily reflect those of the NHS Executive.

We thank Prof Take Yamaguchi, now Emeritus Professor of Neurology, Cardiovascular Division, National Cardiovascular Centre, Osaka, Japan author from the first version in to the third version in and Prof Werner Hacke, Professor of Neurology, University of Heidelberg, Germany author on the first version in for their support on previous versions of this review.

We would also like to thank Brenda Thomas for assistance with literature searching. We would like to thank Ms Kirsten Shuler for entering references and data. Anyone aware of any thrombolysis trials not mentioned herein, or inaccuracies, should please contact us with the relevant information. CT: computed tomography DWI: diffusion weighted imaging i. CT: computed tomography i. None in principle. The original protocol was written in , since when Cochrane Reviews have become more complex, data analyses have been refined and substantially more data have become available for this review.

Notwithstanding, the basic principles of this review are unchanged from the original protocol. Dr Eivind Berge undertook further detailed literature searching for the update. Both Dr Veronica Murray and Prof Joanna Wardlaw reviewed all new trials since and extracted, verified and entered new data for the update. Both Prof Joanna Wardlaw and Dr Veronica Murray checked additional publications since of trials already included in the version for additional new information.

All review authors also contributed to interpretation of the data. Prof Joanna Wardlaw drafted the review and the other review authors contributed to the critical revision of that review and final approval of the version to be published. Further details of competing interests are listed on the Division’s web site www. The review was assembled, analysed and reported independent of any sponsor or pharmaceutical company. Cochrane Database Syst Rev.

Published online Jul Joanna M Wardlaw, Email: ku. Author information Copyright and License information Disclaimer. Corresponding author. This article is an update of on page CD Abstract Background Most strokes are due to blockage of an artery in the brain by a blood clot.

Objectives To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke. Selection criteria Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke.

Data collection and analysis Two review authors applied the inclusion criteria, extracted data and assessed trial quality. Authors’ conclusions Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Background Most strokes are due to blockage of an artery in the brain by a blood clot. Study characteristics We identified 27 trials with a total of 10, participants in searches conducted up to November Background Description of the condition Acute ischaemic stroke is a major cause of death and disability worldwide.

Why it is important to do this review An overview of the literature on thrombolysis in acute ischaemic stroke in Wardlaw identified six randomised trials of various thrombolytic drugs including a total of just participants.

We wished to determine whether: thrombolytic therapy increases the risk of death:. Methods Criteria for considering studies for this review Types of studies We sought to identify all truly randomised unconfounded trials of thrombolytic therapy compared with placebo or open control in people with acute ischaemic stroke.

Types of participants We included trials of participants with a definite acute ischaemic stroke CT or magnetic resonance MR scanning having excluded intracranial haemorrhage prior to randomisation. We assessed the following. Deaths from all causes within the first seven to 10 days after treatment. Symptomatic intracranial haemorrhage SICH : either symptomatic that is, temporally associated with a deterioration in the person’s neurological state , or fatal that is, leading directly to death , and occurring within the first seven to 10 days.

Note that symptomatic intracranial haemorrhage includes haemorrhagic transformation of the infarct, haemorrhage elsewhere in the brain remote from the infarct, and haemorrhage into the spaces surrounding the brain.

Definitions of SICH vary between trials and therefore we have used the SICH data as defined by each trial’s primary definition rather than attempting to standardise the definition. Poor functional outcome the converse of good functional outcome is the most clinically relevant and important measure of outcome, since the aim of treatment should be not merely to avoid death but also to decrease dependency among the survivors; that is, to increase the proportion of independent survivors and conversely to reduce the risk of survival with serious disability.

Dependency in the present analysis was defined as a score of between 3 and 5 inclusive on the modified Rankin Scale mRS. Some would prefer a definition of ‘good outcome’ independence including Rankin 0 and 1 only; therefore, wherever possible we sought data on the number of participants in each individual Rankin category so as to compare poor functional outcome defined as mRS 2 to 6 with the definition of 3 to 6.

Where data were not available for mRS 3 to 6, we used mRS 2 to 6 instead, rather than excluding the trial from analysis. Search methods for identification of studies See the ‘Specialized register’ section in the Cochrane Stroke Group module.

Searching other resources We handsearched the following conference proceedings and stroke and neurological journals: Stroke , Cerebrovascular Diseases , International Journal of Stroke , Journal of Stroke and Cerebrovascular Diseases , Neurology and Journal of Neurology, Neurosurgery and Psychiatry published to March We checked multiple international conference proceedings on stroke and specifically on thrombolysis since We made direct contact with principal investigators of trials in Europe, North America, Japan, China, and Australasia.

We contacted pharmaceutical companies for more information about trials known to exist from the above efforts, and for information on any trials which were so far unknown to us the last systematic contact was made in December ; all companies except one which was known to be doing a trial in any case responded, and no trials were identified that we did not already know about.

Data collection and analysis This review builds on a continuous data collection process that started in Selection of studies Two review authors JW, VM screened the records obtained from the electronic searches and excluded obviously irrelevant studies. Data extraction and management Two review authors JM and VM checked the data extraction and resolved any discrepancies or uncertainties by discussion or clarification with the principal investigator. Assessment of risk of bias in included studies We assessed risk of bias as specified in the Cochrane Handbook for Systematic Reviews of Interventions , Version 5.

For each included trial we collected information about: the method of randomisation including information on allocation concealment ;.

Measures of treatment effect We extracted the number of participants in the treated and control groups who had: died within the first seven to 10 days;. Unit of analysis issues Our definition of SICH included people who died or deteriorated clinically as a result of intracranial haemorrhage. Dealing with missing data We contacted trial investigators to obtain all unpublished missing data where possible. Assessment of reporting biases We have endeavoured to include data from all trials on all prespecified outcomes, obtained from secondary publications or the trial investigators if unpublished.

Subgroup analysis and investigation of heterogeneity We examined the effect of stroke severity, age under or over 80 years, time from stroke to treatment and the effect of having a large infarct on plain CT ASPECT score 7 or less on outcome after thrombolysis.

Sensitivity analysis We examined primarily the effect of the thrombolytic drug in all studies for all drugs combined. Results Description of studies Results of the search The search of the Cochrane Stroke Group Trials Register identified 19 potentially relevant new or ongoing trials, of which only one was completed and relevant IST3 However, this was removed after participants had been recruited into Part A of the trial on 30 March , and thereafter 69 participants over the age of 80 were randomised the oldest participant was 90 www.

One trial excluded people with early visible infarction Wang None of the other trials specified that people with a CT scan that showed an infarct which was likely to be symptomatic should be excluded, although individual doctors may have excluded these individuals in some centres depending on local opinion. Time to randomisation The maximum time interval allowed between the onset of the stroke and the start of the treatment administration varied from within three hours to up to two weeks.

One trial randomised participants within four hours ASK One trial randomised participants between three hours and 4. One trial randomised participants within 24 hours AUST Two trials randomised participants within five days Atarashi ; Ohtomo One trial randomised participants within two weeks Abe Antithrombotic use was not randomly assigned in any other trial and its permitted use varied: in one study ASK all participants were to receive mg aspirin starting within four hours of the streptokinase infusion and continued daily thereafter;.

Excluded studies We excluded two trials conducted prior to the availability of CT scanning Meyer ; Meyer as there was no way of confirming that the stroke was ischaemic. Also in the interests of reducing delays to trial treatment administration, there were some participants who ultimately were not entered into the study after the pharmacy had prepared the trial pack and therefore some discarded trial packs.

Details of the randomisation are given at www. Incomplete outcome data All available data are included. Selective reporting We have avoided, as far as possible, any reporting bias by obtaining original data from the trial investigators where these have not been published. Effects of interventions See Data and analyses. Deaths from all causes within seven to 10 days Data on deaths occurring within the first seven to 10 days were available for 13 trials participants; Analysis 1.

Open in a separate window. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 1 Deaths from all causes within 7 to 10 days. Fatal intracranial haemorrhage within seven to 10 days Data were available from 17 trials on fatal intracranial haemorrhage participants; Analysis 1. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 2 Fatal intracranial haemorrhage within 7 to 10 days.

Deaths within the first seven to 10 days from causes other than fatal intracranial haemorrhage We calculated the effect of thrombolysis on death from causes other than fatal intracranial haemorrhage for the 10 trials that provided data on both early death and fatal intracranial haemorrhage participants; Analysis 1.

Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 3 Deaths within the first 7 to 10 days from causes other than fatal intracranial haemorrhage.

Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 4 Symptomatic including fatal intracranial haemorrhage within 7 to 10 days. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 5 Symptomatic including fatal cerebral oedema. Concomitant antithrombotic drug use It is not possible to comment on the effect of aspirin use prior to the stroke; although some trials recorded prior aspirin use, we could not extract data from the publications in a comparable manner and none of the earlier trials balanced randomisation on prior aspirin use.

Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 14 Deaths from all causes ordered by antithrombotic drug use. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 15 Deaths from all causes ordered by stroke severity.

Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 17 Death or dependency by time to treatment up to 6 hours: all agents: only trials randomising in both 0 to 3 and 3 to 6 hour time windows. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 20 Death or dependency by latest time to randomisation. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 27 Death by latest time to treatment. Analysis Comparison 1 Any thrombolytic agent versus control, Outcome 30 Symptomatic intracranial haemorrhage by latest time to treatment.

Discussion Summary of main results There is strong evidence from 27 trials in 10, participants on the immediate hazards and the apparent net benefit of thrombolytic therapy given up to within three hours of acute ischaemic stroke, with overall benefit suggested up to six hours, for people aged over or under 80 years, and with different stroke severities. Overall completeness and applicability of evidence The trials included in this review are small in comparison with the thrombolytic therapy in myocardial infarction trials.

Potential biases in the review process This review is the result of an ongoing process involving the collaborative effort of many researchers worldwide and the principal investigators of many of the thrombolysis trials. Authors’ conclusions Implications for practice. Faster treatment is more beneficial. People treated within three hours of stroke are less likely to be dead or dependent than those treated after three hours, although some may still derive benefit if treated up to six hours.

There is, overall, proof of an excess risk of symptomatic and fatal intracranial haemorrhage and early death from all causes with thrombolytic therapy. Evidence on risk factors, however, is incomplete. Despite the overall net benefit, the available data do not provide sufficient evidence to determine the duration of the therapeutic time window, the clinical or radiological features which identify those most likely to benefit or be harmed including whether or not people with mild stroke benefit or not, or the optimum agent or dose or route of administration.

The data indicate that antithrombotic treatment should be avoided until at least 24 hours after thrombolytic treatment. While the data suggest that some people may benefit even up to six hours, change in clinical practice should await results of further trials to determine the latest time window for benefit. Implications for research. To provide data on the latest time window for treatment in which people and by what means of selection;.

Feedback Concomitant use of antithrombotic treatment Summary Category: Methodological qualities of included studies This review The Cochrane Library Issue 1, states that “.. Reply Wardlaw et al have tried to contact Haley et al but without success. Reply We thank Brian Alper and colleagues for their interest in our review, and for their comments. In the Risk of bias in included studies section, it would be helpful: 1 to include a risk of bias summary table. However, we clearly state the major issues related to bias in the text and state in the Methods in ‘Assessment of risk of bias’: “We assessed risk of bias as specified in the Cochrane Handbook for Systematic Reviews of Interventions, Version 5.

Feedback, 11 November Summary We previously provided feedback dated March 21, and your many responses to numerous concerns did not address a highly specific concern regarding the baseline difference in history of prior stroke in ECASS III, and how adjusting for this may negate any evidence of efficacy for alteplase 3 to 4.

Reply We thank Dr Alpers and colleagues for their continuing interest in the review of thrombolysis in acute ischaemic stroke.

We note two further points. None of the trials were especially large. As we explain in the review, a consequence is that several trials go from positive to neutral, or neutral to positive, simply by switching between mRS 0 to 1 and mRS 0 to 2, or between mRS 3 to 6 and mRS 2 to 6 as the outcome.

Figures 1. This illustrates that the data should be viewed in totality rather than focusing too closely on individual trials, which of course is the purpose of Cochrane reviews. However, several other trials also randomised in that time window although not exclusively. Unfortunately, as explained in a previous response, not enough of those trials published tabular data on the 3 to 4. Thrombolysis with alteplase 3 to 4. History Protocol first published: Issue 1, Review first published: Issue 1, Date Event Description 12 May Feedback has been incorporated See Feedback 2 2 April New search has been performed We have updated the searches to November with further handsearch to March We have added new information from previously published trials and several new analyses of new and existing outcomes.

Markers of risk for early intracerebral haemorrhage are still unidentified. Information about the organisation of the NINDS trial randomisation method and resulting problems have come to light.

A new trial from China of intravenous urokinase within six hours is included. A plain language summary has been added. Acknowledgements Although supported in part by a grant from the NHS Executive, the opinions and views expressed in this update do not necessarily reflect those of the NHS Executive. Appendices Appendix 1. Appendix 2. Notes Edited no change to conclusions , comment added to review.

Data and analyses Comparison 1 Any thrombolytic agent versus control. Outcome or subgroup title No. Characteristics of studies Characteristics of included studies [ordered by study ID] Abe ASK Haemaccel given plasma expander should the BP fall below mmHg systolic or by more than 20 mmHg from the initial systolic BP during the infusion This procedure to be repeated should hypotension occur again, but the infusion to be completed within 3 hours or abandoned Aspirin mg to be given orally within 4 hours of the trial treatment infusion and thereafter daily for the duration of the study No other anticoagulants to be given within 48 hours of the trial treatment Outcomes Death and dependency at 3 months assessed by the Barthel Index, i.

Atarashi AUST Chen DEDAS DIAS 2 DIAS ECASS ECASS 3 University of Southern …. Preisler, A. Fabricius, H. Haberland, S. Risage Eds. The consequences of mobility: Linguistic and Sociocultural Contact Zones pp. Marta Gonzalez-Lloret. Michael Handford. Multilingualism at work: from policies to practices …. Birgit Apfelbaum. Mie F Nielsen. Zhu Hua. Arja Piirainen-Marsh. Lenore Manderson. Karen Grainger. Georges Luedi. Bal Krishna Sharma. Paul Seedhouse. Cade Bushnell. Anna Charalambidou , Kristina Ganchenko.

Ifigenia Papageorgiou. Jason Turowetz. Genevieve Maheux-Pelletier. Rue Burch. Log in with Facebook Log in with Google. Remember me on this computer. Enter the email address you signed up with and we’ll email you a reset link. Need an account? Click here to sign up. Download Free PDF. Identities at odds: embedded and implicit language policing in the internationalized workplace. Abstract This study offers an interaction analytic account of how linguistic identities in internationalized workplaces in Denmark are indexed against members’ institutional positions in particular interactional contexts.

Related Papers. Journal of Pragmatics 62 Moving into interaction – embodied practices for initiating interactions at a help desk. Moving into interaction: Social practices for initiating encounters at a help desk. Embodying the institution: Object manipulation in developing interaction in study counselling meetings.

Conversation Analysis for Intercultural Communication. Symposium proceedings: Challenges and new directions in the micro-analysis of social interaction. Introduction: A body of resources – CA studies of social conduct. Language and Intercultural Communication, Vol. Where language policy may not be explicitly articulated between members, it is still embedded in how participants micro- manage their interactions and implicit in how members display orientations to deviance, in the case of encountering others in the workplace whose language repertoires or preferences do not meet with expectation pertaining to the institutional position they hold.

Het onderzoek keek naar hoe verschillende taal identiteiten vergeleken werden met werknemers’ institutionele functies, tijdens werkactiviteiten uitgevoerd samen met anderen. Keywords: linguistic identity; language policy; language choice; institutional identity; internationalization Introduction Workplaces around the world have increasingly come to be constituted as communities of transnationally mobile staff and clientele, and the resulting cultural and linguistic diversity to which this gives rise.

Hazel language scenarios Mortensen, as part and parcel of their ongoing daily workplace activities e. This in turn requires members to remain sensitive to a shifting bricolage of linguistic identities Gafaranga, encountered at any given moment as they go about their work-related activities, in order to be able to respond appropriately, effectively and efficiently to each linguistic scenario as it arises. The paper will argue for greater attention to be paid to the actual language-political practices in international workplace settings, as an entry point into developing a more nuanced understanding of the practices through which professional identities are brought about, affirmed and contested, and the linguistic considerations that are implicated in this.

This would complement research strands that investigate language policy, ideology and attitudes through a focus on official documentation or by drawing on qualitative research methods such as focus groups and interviews. A growing number of institutions have moved to adopt formal policies pertaining to language practices — including that at the level of language choice — in the workplace e. Such explicit language policing may be introduced to respond to the changing demands that result from increased globalization, including the internationalized make-up of a particular institutional community, be it, for example, a company operating across borders or with greater numbers of migrant professionals, foreign-based clients or partners in other parts of the world, at popular tourist attractions or at particular institutional programmes within tertiary-level education.

However, such language-policy strategies may not apply, or be appropriate, to all settings within a workplace community, or indeed reach all relevant parties. Furthermore, individual members may also hold entrenched ideological positions of their own pertaining to the relative value of the use of particular languages within a setting or to language requirements relating to institutional positions within a particular workforce.

Hence, backroom language policies may not be implemented or adhered to across all settings within a workplace community, and this necessitates members to remain prescient to the dynamics of such transient multilingual settings Goebel, In linguistically dynamic environments where language choice is then not predeter- mined by formal institutional policy, e.

Here, where language policy may not be explicitly discussed between members, it is still embedded in how participants micro-manage their Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January interactions. For example, Mortensen shows how locally established norms for language choice within student project groups are evidenced in how the members orient to the appropriateness of one or other language for engaging in particular activities, such as on-task or off-task talk.

Elsewhere, in encounters where participants have no prior experience of interacting with one another, participants must also work together to alight upon the medium which best suits the parties involved and the institutionally oriented activities in which they are engaged Heller, ; Torras, Social science has occasioned a number of lines of investigation characterized by a focus on situated social action and interaction observed in their natural everyday habitats.

The methodological perspective applied in the current study has its origins in the American sociological approach to language and social interaction, known as Ethno- methodology Garfinkel, ; henceforth EM.

In EM, the study of human sociality is premised on an understanding that there are methods of which members of a society avail themselves in their understanding, production and navigation of their social world. Social order is considered here an achievement by the participants, who rely on their common-sense knowledge of situated action in order to accomplish, in situ, orderliness in their conjoint social activities.

Hazel MCA by explicating the procedures through which members associate particular activities or characteristics — predicates — with particular categories of people Sacks, Such research explores the relevance of person categorization to the understanding and assessment of conduct, and the consequent importance of understanding how categories are made relevant, even if tacit, in ordinary conduct of interaction.

Schegloff, , p. With CA and MCA using audio recordings and increasingly audiovisual recordings of — and artefacts stemming from — social engagement in its natural ecology, the research methodology offers powerful tools to unpack and describe the situated social processes involved in workplace organization.

Consequently, these lines of investigation have been strongly represented in applied research, highlighting the situated nature of social action, with important interaction analytic research being carried out in such institutional sites of engagement as business meetings e.

Murphy, , health care e. Raudaskoski, The present study aims to contribute further to this field, investigating what implications the widespread internationalization of workplace settings has for the members, including the interactional competencies relevant to the navigation of such interactional settings.

We turn now to build an empirical account of some such displays and to demonstrate how deviation from normative interactional patterns by members of the community can impact upon their status as member of their institutional category.

Data for the current study were collected by the author in internationalized workplace settings, including international university settings1 see Hazel, , and international companies in Denmark. Transcription conventions are based on those developed by Gail Jefferson ; further explanation provided in Appendix 1. Each may reveal a different language policy. The way people speak, the way they think they should speak, and the way they think other people should speak may regularly differ.

Looking at the language policy of established nations, one commonly finds major disparities between language policy laid down in the constitution and the actual practices in the society. Within social groups, it is common to find conflicting beliefs about the value of various language choices.

One is therefore faced regularly with the question of which the real language policy is. Spolsky, , p. These in turn constitute interactional norms. As Bonacina-Pugh , p. Regularity, recognizable practices and underlying norms may point to relatively stable communities, where members rely on shared understandings, and members whose practices do not correlate with overall normative expectations may be interpreted by others in the community as somewhat deviant.

Indeed, they may be treated as such also. By looking at the ways the participants treat these interactional moments, an analyst is able to identify the related normative expectations.

Furthermore, they offer valuable insights into the ways in which members of a community are constituted as being deviant. Embedded language policing The following example is taken from a departmental meeting situated in an international company in Denmark, composed by a nationally heterogeneous workforce where transnational mobility is a common feature.

The meeting has until this point been conducted in English, which here acts as a regularized lingua franca — for this type of activity — between the participants, who are from different European countries. The practiced language policy in evidence here — with English adopted as a corporate lingua franca — appears to be premised on how the team is constituted through members from different language backgrounds, and with new members joining and others leaving the team on occasion to work in other departments within this multinational company.

As she does this, a third member of the team ANNa interjects with a comment. Hazel Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January We note in the example how Anna provides a critical comment to her line manager Ulla line 15 , where she raises an issue relating to her own request for work-at-home days, a decision where she feels she has been slighted.

Importantly, we see how this interjection is treated as the voicing of a grievance by the manager Ulla, who in response provides an account for the decision lines 17 and This appears then to evidence a workplace culture where managers can be challenged by their subordinates and explicitly held to account for their decisions.

Not only do we observe the challenge, but we also see that the manager orients to this as not necessarily a welcome trajectory but valid all the same. Although complaints make a variety of responsive turn types or action types relevant Schegloff, , for example, remedial actions, excuses, apologies and the like, here Ulla produces an account for her decision to only allow Anna a single extra work-at- home day.

Although the complaint is thus not addressed in a remedial way, but instead rejected, the rejection is formatted as a dispreferred response on preference organization, see Pomerantz, : it is delayed, it includes an account for the decision and furthermore mitigates the rejection with a further account of how Ulla has already gone out of the way to make exceptions. Pertinent to the study here, we note that the language chosen for providing the comment in line 17 is Danish, not English as in the rest of the meeting, and the side sequence that this occasions, is initially pursued in Danish.

Language and Intercultural Communication In this way, the choice of language used in a first pair part adjacency pair e. In the current sequence, this means that the unmarked choice for the manager here is to respond in Danish, which she does. The example demonstrates how when members display language choice preferences that do not correlate with the prevailing practiced language policy in the sense described by Spolsky and Shohamy [] and Bonacina-Pugh [] , they can be publicly sanctioned, with their language selection overruled.

This includes transparency, where decisions are understood by all, not just those more closely connected. Although this example is drawn from a transient multilingual setting, there is enough group stability for practices to become routinized, even within the ongoing changing membership of the team. Elsewhere, however, members face the necessity of having to enter into encounters with people they have never met previously. Here, participants must coordinate or negotiate language-policy practices on the spot, including at the level of appropriate language choice.

As they do so, so we gain access to normative expectations relating to the matter. It is this that we turn to now. A number of resources appear to facilitate them in settling on an operational medium for interaction. Some of these relate to membership categorization, through which they may project certain expectations relating to the language competencies and preferences of their incipient partners-in-interaction. Not all membership categories here are relevant. Gender, for example, sexual orientation or age Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January group categories would be wholly irrelevant to the linguistic identities of the interlocutors-to-be.

However, there are membership categories — for example those pertaining to ethnic or racial background, geographic residence, or institutional identity — that appear to be used as a resource for discerning the probability for possible language preferences or competencies on the part of the unacquainted other. Someone with an East-Asian appearance may, for example, be judged less likely to have proficiency in Portuguese, than someone with Latin-American features.

Regardless of the obvious margins of error that such categorization practices engender, people seek to reduce the levels of complexity when faced with social life in all its messy, diverse glory. Here, identities are brought into being discursively, worked up as respective relational identities relevant to the interaction in which they are engaged e. As with the identity constructs described above, these membership categories too may engender particular associations, e.

It follows that such membership category predicates are useful tools, but only when the particular social identity is oriented to as being relevant to the business at hand. As way of illustration, consider the following extract, which serves to demonstrate how linguistic identities are implicated in certain social membership categories.

Anita initiates her account for attending the help desk in English lines 21 and She does this immediately, without any preliminary request as to whether this is an appropriate choice. This displays a projection on her part that the member of staff is able to deal with the service encounter in English and that this language selection would be neither problematic, nor unexpected, for the given setting.

For her part, the staff member triggers a switch to Danish once it becomes clear what is projected as the topic of the service. As soon as Anita announces that the students are interested in a study exchange abroad line 24 , she asks whether they are Danish speakers line The staff member initially responds in English line 26 , though breaking off almost immediately and switching to the local language for the remainder of the turn, in which she asks whether they speak Danish.

Interestingly, she projects her understanding that they are Danish speakers through the language choice in which she produces the question, namely Danish. The students confirm that they are able to speak Danish, which calls attention to their capacity to use of the language, rather than it being their default.

This in turn prompts the staff member to offer a further candidate understanding that they are not from Denmark line Brigitta confirms this, in Danish, by self-categorizing herself and her partner as hailing from Germany. This suggests that she has now been able to fully re-calibrate the categorization of the students, bringing the insertion sequence to a close. Anita subsequently reformulates her earlier turn in which she set out the reason for the visit, this time in Danish lines 42 and Where reality intervenes and expectations are uncorroborated, work is undertaken to re- calibrate the misalliance between expectation and actuality.

In what follows, we will explore this further and demonstrate how such sequences of misalignment between institutional and linguistic identity may act to undermine the institutional position of a member of the community, by orienting to them as not type-fitting the institutional position relevant to the encounter. This, I will argue, is a form of implicit language policing, where members are treated as not conforming to their professional identities, on the basis of an absence of some or other expected linguistic resources.

Across all types of approach, a common pair of patterns for entering into the focused encounter is represented in the following transcripts, represented in examples 3—6.

The upshot is that the linguistic code is at this stage ambiguous. We note two patterns: the first involves the staff member STA producing the first greeting with the client CLI responding. Language and Intercultural Communication Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January This allows for the client to respond in the same language and to proceed to the next turn where the medium becomes disambiguated, either as Danish as in the first example or as English as in the second.

The second pattern has the first greeting produced by the client, with the member of staff producing the return greeting. Here, the staff member is in the position to treat the first greeting produced by the client as either Danish or English. The client is then in the position to treat this return greeting as either Danish or English and to proceed to formulate the next turn in that medium of interaction.

The above patterns for entering into a service encounter at this International Office help desk evidence a particular organization of affording the client the right to select one of a number of languages to serve as medium for interaction, here Danish or English. It is always the client who is afforded the turn where the language becomes disambiguated. This in turn demonstrates categorization work carried out by the participants, who at this incipient stage of their focused encounter are able to display within their turn organization an institutional orientation, with an asymmetrical distribution of interactional rights and obligations.

Secondly, these membership categories are linked with particular category- bound associations relating to language repertoires. Routinized practices such as those described here pass off in an unmarked — seen-but- unnoticed — fashion, as has been described for normatively appropriate social conduct in general Garfinkel, Analyses of cases that deviate from the regular interactional patterns can provide us with a useful second level of analysis.

These instances provide us with further insight into what normative expectations are present, according to which parties orient themselves in the particular setting at hand. Hazel In the current data-set, there are a number of these deviant cases, where the step-wise move into this business-at-hand is momentarily suspended along the same lines as discussed in Example 2.

Here, we will discuss one of the instances where it is the staff member whose language repertoire becomes a topic requiring attention prior to the service encounter proceeding. In this excerpt, a client approaches the help desk counter and he and the staff member enter into an encounter. However, the meeting hits trouble when the staff member initiates medium repair Gafaranga, from Danish to English.

We note the canonical opening sequence described earlier lines 17— Following Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January this pattern the client is again in the position to treat the second greeting, produced by the staff member in response to his own, as being in either English or Danish.

He subsequently embarks on formulating the topic of the enquiry, selecting Danish to do so. He offers an apology for not being able to speak Danish, formatted with laughter tokens lines 25 and This is a preferred next action to an apology Robinson, The client subsequently restarts his turn, this time in English. The participants here negotiate an explicit repair of the medium of interaction Gafaranga, , but what is more, it is produced in a dispreferred format Pomerantz, ; Schegloff et al.

Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January The lack of Danish is thus arguably treated as a relevant deficiency on the part of his membership in the category relating to his institutional position.

The staff member is oriented to by both parties as not type-fitting the membership category relating to his institutional identity, with Danish being accountably absent. Breaches in the everyday normality or affairs attract attention, result in anxiety, moral and psychological evaluations even, and can threaten the status of the breacher, in this case the member of staff. Schegloff , p. Of course, this is not treated explicitly as problematic on the part of those who come into contact with him: it is implicit in the way expectations are displayed as requiring recalibration.

With each occasion potentially flagging up the misalignment between the institutional position that he holds and his linguistic repertoire, these repair sequences may then act to undermine his institutional identity and confidence as a fully competent member of staff, indeed potentially bringing about a marginalization of particular members of the workplace community.

This supports findings documented elsewhere by survey- based studies such as those by Ehrenreich and Neeley Coda: adopting strategies for avoiding explicit medium repair Elsewhere Hazel, in press , I have described a number of strategies not always successful that this particular member of staff has adopted, which serve to circumvent the type of interactional trouble analyzed here, and micro-manage the entry into the encounter.

First there is the pre-emptive strike, where he avoids the greeting sequence altogether and opens the interaction with a turn that is clearly, unambiguously English. The adoption of such strategies would appear to indicate a disposition to avoid such situations where his linguistic identity is indexed against his institutional membership category, with the potentially negative ramifications for his professional identity.

Where these linguistic identities do not meet with normative expectations regarding a particular institutional position, this may be flagged by the parties as deviant, and business that needs attending to for the interaction to proceed. This perceived deviance may in turn act to unintentionally compromise the institutional identities of particular members of the community, leading to potential marginalization.

For example, a particular category-bound predicate associated with the institutional status of team members in an international company in Denmark is the unproblematic, confident use of English during workplace meetings, regardless of the personal preferences or competences of the team members to do so. Elsewhere, in a Danish university setting, international students are expected to lack proficiency in the local language, while staff at the International Office help desk are expected to be at least bilingual in Danish and English, regardless of their institutional role within the organization.

In the same way a member of staff can be held accountable for being unable to accommodate the line manager or the client in terms of carrying out their job, or addressing the particular issue that has prompted a service encounter, the staff member can also be held morally accountable for what language repertoire is available for carrying out the tasks. The current paper has sought to demonstrate how empirical accounts of situated language practice can enhance our understanding of how language policy, language ideology and language attitudes play out in the field, with consequences for the institutional or professional identities of the members in these communities.

The particular emic perspective developed through CA- and MCA-inspired analyses is especially beneficial here, as it allows for researchers to develop empirically grounded accounts of the ways in which members in the workplace communities produce social Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January order in situ, through the micro-managed social practices evidenced in interaction, including sequential organizational practices of turn-taking, repair strategies, accounting practices and orientations to deviance.

The corrective offered here and in similar work elsewhere e. Day, ; Markaki et al. Ehrenreich, ; Mahili, ; Neeley, , ethnographic observation or mixed-method approaches that combine ethnographic fieldwork with survey tools e.

Rather, interaction analytic accounts such as the one presented here aim to contribute to this field of scholarship, by offering insight into the moment-by-moment enactment of social order, including at the level of identity negotiation.

I will discuss this with two examples. First, interaction analytic research can offer additional nuance to studies in the field of transnational mobility. For example, where a recent critique by Canagarajah has sought to offer greater granularity to the sociolinguistics of globalization as represented by Blommaert and colleagues e. More immediate scrutiny of the interactions in which people are involved, as featured in the current study, affords both of these lines of research a window into how such agency is constituted, contested, negotiated and resolved between the parties to these encounters in situ.

Hence, we are able to develop a different level of insight: that of how participants display between one another their respective understanding of what norms, expectations, rights and obligations are deemed relevant for this moment, in this activity, in this setting with respect to language and indexicality. Consequently, we are in the position to build up a fuller, more fine-grained account of the fleeting moments where identity work is being occasioned, where people place one another within a matrix of social order; practices which would be difficult to explicate through even the most detailed accounts elicited through survey tools such as interviews.

Hazel how this impacts on their position, self-esteem and perceived agency within their workplace communities, interaction analytic investigations can shed light on the very processes from which these accounts result.

Second, this line of research continues to add to theoretical work on discursive identities, and more broadly on theorizing identity. Looking at the internationalized work setting, Lauring , for example, explores how L1 differences may impact on the formation of in-group social identities among workplace members. Here, he critiques Social Identity Theory e. Tajfel, with what he perceives as its linear link between language and identity, criticizing this conceptualization as too deterministic and static and Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January arguing for a more dynamic consideration of language use as a means for strategic self- representation in the transnational workplace.

With an increasing number of institutional settings becoming internationalized, the findings presented here have important implications for workplaces characterized by transnational mobility.

Increasing an awareness of social practices that link professional identities with other social identity constructs such as ethnicity, nationality or in this case linguistic identity, can 1 prepare the ground for avoiding the potential pitfalls of group fragmentation, anxiety, alienation and isolation experienced by particular members of the workplace community e. The shifting sands of the increasingly transnational workplace settings that have recently become so commonplace across the globe offer both practitioner and researcher an opportunity to reconsider sedimented understandings of community membership and belonging, social identity formation and workplace practices, and explore afresh the dynamic processes involved in the constitution of workplace — and other types of — communities.

Notes 1. Prior to the formal proceedings of the meeting commencing, as well as during breaks in the meetings, participants use other languages also. Interestingly, Anna, who appears to be insisting on a right to use Danish with her Danish manager, is not herself a Dane, but is from Sweden albeit someone who has lived in Denmark a number of years , and appears therefore to be claiming the right to use a different L2 than English.

A reviewer of the current article has pointed out that if these greeting tokens are produced with rising intonation, it is likely to be heard as a Danish hej rather than an English hi. This would definitely be the case for many settings. However, the data from this setting do not seem to bear this out, as there is a great deal of variation in how the L2 users of both English and Danish produce these tokens, including at the level of intonation contour.

Participants are unable, then, to treat this as a reliable marker for the use of hej or hi. Language and Intercultural Communication 6. Disclosure statement No potential conflict of interest was reported by the author.

He has Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January published widely in CA informed research on social conduct, including embodied actions in everyday and institutional interactions. His research interests include cultural encounters, multi- culturalism and learning. References Angouri, J. Multilingua, 33 1—2 , — Antaki, C. Identities in talk.

London: Sage. Auer, P. Bilingual conversation. Amsterdam: Benjamins. Bargiela-Chiappini, F. Marra Eds. Basingstoke: Palgrave Macmillan. Blommaert, J. The sociolinguistics of globalization. Cambridge: Cambridge University Press. Bonacina-Pugh, F. Language Policy, 11, — Brassac, C. Interweaving objects, gestures, and talk in context. Mind, Culture, and Activity, 15 3 , — Canagarajah, S. Agency and power in intercultural communication: negotiating English in translocal spaces.

Language and Intercultural Communication, 13 2 , — Globalization and language in contact: Scale, migration, and communicative practices. London: Continuum. Day, D. Pragmatics, 4 3 , — Deneire, M. English in the French workplace: Realism and anxieties. World Englishes, 27 2 , — English as a business lingua franca in a German Multinational corporation: Meeting the challenge. Journal of Business Communication, 47, — Medium repair vs.

International Journal of Bilingualism, 4, — Gafaranga, J.

 
 

Thrombolysis for acute ischaemic stroke – PMC –

 

Думаю. У нас есть кое-какие данные. Танкадо неоднократно публично заявлял, что у него есть партнер. Наверное, этим он надеялся помешать производителям программного обеспечения организовать нападение на него и выкрасть пароль. Он пригрозил, что в случае нечестной игры его партнер обнародует пароль, и тогда все эти фирмы сойдутся в схватке за то, что перестало быть секретом.

 

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The new PMC design is here! Learn more about navigating our updated article layout. The PMC legacy view will also be available for a limited time. Federal dowmload websites often end in. The site is secure. Most strokes are due to blockage of an artery in the brain by a blood clot.

Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Ffree drugs, however, can also cause serious bleeding in the brain, which can be fatal. Forty per cent more data are available since this review was last updated in frer To determine whether, and in what circumstances, thrombolytic therapy beqr be an effective and safe treatment for acute ischaemic stroke.

We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists. Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke. Two review authors applied the inclusion criteria, extracted data and assessed trial нажмите чтобы прочитать больше. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available.

Most data come from trials that started treatment up to six hours after stroke. In earlier studies very few drife the participants 0. Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review.

Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or извиняюсь, best sound recording software for pc free download идея modified Rankin 3 to 6 at three to six months after stroke odds ratio OR 0.

Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage OR 3. Early death after thrombolysis was перейти на страницу attributable to intracranial haemorrhage.

Treatment within three hours of stroke was more effective in reducing death or dependency OR 0. There was heterogeneity between the trials. Contemporaneous antithrombotic drugs 327 hazel drive bear de free download the risk of death. Bewr aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three 327 hazel drive bear de free download по этой ссылке stroke. Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people.

Those treated within the first three hours derive substantially more benefit than with later treatment.

Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice.

Thrombolytic drugs can also, however, cause serious bleeding in the brain, which can be fatal. Thrombolytic therapy has now been evaluated in many randomised trials in acute ischaemic stroke. The thrombolytic drug alteplase has been licensed for use within three hours of stroke in the USA and Canada, and within 4.

The numbers of people receiving взято отсюда treatment successively are increasing. We identified 27 trials with a total of 10, participants in searches conducted up to November Most trials included participants with moderate to severe stroke. All trials took place in hospitals that were used to treating people with stroke. Differences between trials mean that not http://replace.me/15308.txt trials contribute information to all outcomes, but we have used all available data.

Most trials included participants after a computed tomography CT brain scan had excluded a brain haemorrhage as the cause 327 hazel drive bear de free download symptoms a few trials used magnetic resonance brain scanning instead. Older people benefited as much 327 hazel drive bear de free download younger people. Further analyses of individual patient data factors such as findings on brain scanning before treatment, and of different ways of giving the treatment, may give more information than the summary data that we used here.

They should not hesitate by thinking that they will be ‘too old’ for treatment. The treatment is very effective if started within three hours of stroke and definitely improves outcome if given up to 4. These results apply to a wide range of people with a wide drige of severities of stroke and other medical conditions.

Acute drkve stroke is a major cause of death and disability worldwide. Most strokes are due to blockage of an artery in the brain by a blood clot ischaemic stroke e. Some are extracted from biological samples e.

An overview of the literature on thrombolysis in acute ischaemic stroke in Wardlaw identified six randomised trials of various thrombolytic drugs including a total of just participants. A Cochrane review published in Wardlaw updated the original review.

It was updated again in participants in total Wardlawin participants Wardlaw bin participants Wardlaw but even so, many essential questions remained unanswered: How big is the overall benefit? What is the latest time window in which the treatment is still beneficial?

Which grades of stroke severity and which types of stroke, as judged clinically and on brain источник, are more likely to respond favourably to treatment? Should people aged over 80 years receive thrombolysis? Which types of patients are most likely to be harmed by treatment, and which to benefit from it 327 hazel drive bear de free download.

To answer these questions reliably, and in particular to be able to tailor treatment to the individual, more data are needed from new randomised controlled trials RCTs. Guidelines recommended that thrombolysis should be delivered downloar a clinical team with suitable training and experience and in a setting with appropriate facilities ESO Stroke Guidelines ; NICE Stroke Guideline A general review of the use of thrombolytic therapy in clinical practice and the clinical service required to deliver it was provided in a book on the management of stroke Warlow This updated review includes all trials completed and made public sinceas well as additional data published since from trials included in earlier versions of the review.

The upper drjve limit of 80 years, stroke drivve and new imaging data are also analysed. We wished to determine whether:. We sought to identify all truly randomised unconfounded trials of thrombolytic therapy compared with 327 hazel drive bear de free download or open control in people with acute ischaemic stroke. We included trials in dowlnoad the exact method of randomisation was unknown, even after хорошо. pes 2017 pc full version free поржал with the authors, if the available information suggested that the randomisation was not 327 hazel drive bear de free download to be biased.

We included trials of participants with a definite acute ischaemic stroke CT or magnetic resonance MR scanning having excluded intracranial haemorrhage prior to randomisation.

We excluded trials that were confounded by the treatment or control group receiving another active therapy which had not been factored in to the randomisation for example, thrombolytic drug plus another agent versus placebo, or thrombolytic drug versus another agent. We considered all other outcomes as secondary.

See the ‘Specialized register’ section in the Cochrane Stroke Group module. We searched for all trials in all languages using the following overlapping methods, and arranged translation of relevant papers published in languages other than English.

This review builds on a continuous data collection process that started in Two review authors JW, VM screened the records obtained from the bera searches and excluded obviously irrelevant studies. We sought additional unpublished information from the principal investigators of all the trials that appeared to meet our inclusion criteria.

We resolved any disagreements by discussion. The selection for update was verified by EB. Two review authors JM and VM checked the data extraction and resolved any discrepancies or uncertainties by discussion or clarification with the principal investigator. We assessed whether the method of randomisation would allow allocation concealment, the adequacy of efforts to blind treatment administration and outcome assessment. Перейти each included trial we collected information about:.

We provide detailed ‘Risk of bias’ tables for the trial included since the last update. We extracted the number of participants in the treated and control groups who had:. We also extracted data to perform subgroup analyses on time to treatment, age, stroke severity, prior or concomitant antithrombotic drug use, 327 hazel drive bear de free download attempted to find information on pretreatment brain imaging findings, blood pressure, and diabetes details below.

Our definition of SICH included people who died or bar clinically as a result of intracranial haemorrhage. We have defined ‘early after the stroke’ as within the first seven to 10 days, as the trials each tended to use a slightly different time point, but all had collected information on intracranial 327 hazel drive bear de free download certainly within the first 10 days.

Many symptomatic haemorrhages actually occurred within the first few days of the stroke. Thus the true number with Dfive may be higher than that suggested by these data. On the other hand, heightened awareness of an association between haemorrhagic transformation and thrombolysis may mean that the investigators too readily attributed any neurological deterioration following treatment to intracranial haemorrhage, even if the amount of blood was small.

Therefore, it is also possible that the risk of intracranial haemorrhage has been overestimated Von Kummer Most parenchymatous haemorrhages were associated with symptoms, so we used the number of participants with parenchymatous haematoma as the number with symptomatic haemorrhages. We contacted trial investigators to obtain all unpublished missing data where possible. Where data were still missing or had not been collected in the original trial, then that trial did 327 hazel drive bear de free download contribute to the relevant downpoad.

We clarified missing or unclear data with the principal investigator. The outcomes in two studies were very clearly described in the original texts and verification with the principal investigators was not necessary Haley ; Morris Heterogeneity might arise from a wide variety of factors, such as the design of the trials, 327 hazel drive bear de free download type of participants included, the use of concomitant treatments like 327 hazel drive bear de free download or heparin, ancillary care during the acute treatment period or rehabilitation, lack of availability of certain data for a particular trial so that a trial appears as missing for a particular outcome, or simply by the play of chance, particularly in small trials Deeks ; Higgins We have endeavoured to include data from all trials on all prespecified outcomes, obtained from secondary publications or the trial investigators if unpublished.

We assessed the likelihood of missing trials using a funnel plot. 327 hazel drive bear de free download calculated absolute numbers of events avoided or caused per patients treated using the risk differences method provided in the Deive Manager 5 software RevMan and also as the straight percentages calculated from the number of events per number randomised in the treated and control groups.

However, please note that these events per treated data should be regarded with caution as they rownload produce misleading results, since the absolute risk amongst controls varies between trials. We examined the effect of stroke severity, age under or over 80 years, time from stroke to treatment and the effect of having a large infarct on plain CT ASPECT score 7 or less on outcome after thrombolysis. We assessed the effect of time by bsar approaches: we examined the effect of time in all trials regardless of what time windows they contributed to, then in only those trials that contributed to all time windows, and then by latest time to randomisation.

These approaches were used to maximise use of available data and minimise bias by excluding some trials from some analyses e. We used the proportion who died in the control group to estimate the severity of stroke.

We assessed:. We examined primarily the effect of the thrombolytic drug in all studies for all drugs combined. We assessed whether the effect of thrombolysis on functional outcome varied with the definition of dependency mRS 2 to 5, instead of 3 to 5.

We stratified trials by the proportion of participants given aspirin or heparin within the studio 19 ultimate crack serial keygen (final) download period by time after stroke.

 
 

 
 

By using our site, you agree frive our collection of hazdl through the use of cookies. To learn more, view our Privacy Policy. To browse Academia. This study offers an interaction analytic account of how linguistic identities in internationalized workplaces in Denmark are indexed against members’ institutional positions in particular interactional contexts.

Where language policy may not be explicitly articulated between members, it is still embedded in how participants micro-manage their interactions dree implicit in how members display orientations to deviance, in the case of encountering others in the workplace whose language repertoires or preferences do not meet with expectation pertaining to the institutional position they 327 hazel drive bear de free download. The study uses recordings of naturally occurring interaction in different international workplace settings and argues for greater attention to be paid to the actual language-policy practices in international workplace settings, as an entry point into developing a more nuanced understanding of the practices through which professional identities are brought about, affirmed or contested, and the linguistic considerations that dee implicated in this.

Spencer HazelKristian Mortensen. Opening an interaction этим vmware fusion 7 documentation free этом a crucial step in establishing and maintaining social relationships. 327 hazel drive bear de free download this paper we describe how participants in an institutional setting, a help desk counter for exchange students at an international university, literally move into interaction. This is accomplished through a range of publicly available and sequentially organised movements in space.

All rights reserved. Kristian MortensenAdam Brandt. The final version of this paper appears in the collection ‘Research Methods in Intercultural Communication’, edited by Professor Zhu Hua. Spencer Hazel. Lending bureaucracy voice: Negotiating English in institutional encounters This chapter presents a small set of micro-analytic studies of interaction in institutional encounters at a Danish university which illustrate 327 hazel drive bear de free download English in the context of university internationalisation is habitually called upon to verbalize concepts and practices which are intimately tied to local settings but which do not necessarily have direct equivalents in English.

Drawing on methods and theoretical insights originating in the conversation analytic tradition, we demonstrate how speakers как сообщается здесь expressions for local bureaucratic terms and procedures as well 327 hazel drive bear de free download their meaning, and argue that such instances of joint meaning making carry the potential to 327 hazel drive bear de free download to the hyper-local emergent register of English found in the setting.

A key finding of the analysis is that speakers in the data are afforded different epistemic rights and obligations with relation to the lingua franca being used depending on their institutional role, inter national status and general нажмите для продолжения with the linguistic resources used.

English first language speakers are shown to be positioned as linguistic norm providers in several cases, but haael who dfive English as a foreign language also have a 327 hazel drive bear de free download in introducing new terms and redefining old ones, particularly when they use English to lend bureaucracy voice in interactional roles associated with institutional power.

Methodologically, the chapter makes a case 327 hazel drive bear de free download the detailed study of social interaction in transient multilingual communities as a window on linguistic and social change which may stimulate cross-fertilization between the general research areas of sociolinguistics, particularly the study of language variation and change, and the emerging body of research on the use of English in lingua franca scenarios.

International Perspectives on the ELT classroom interaction. Spencer HazelJohannes Wagner. This study offers an empirical account vownload the use of English in Danish-as-a-foreign-language classroom settings. We refer to English as the lingua franca – which in itself is a second language for the majority of the participants in the data – and to Danish as the target language.

We consider implications of lingua franca interaction in target language classroom interactions, and show how in sequences where participants orient to linguistic issues in the target language, for example grammatical forms or lexical items, they often bera this with reference to the lingua franca.

Adam Brandt. Complementing recent interactional research on the contingent operation of online task accomplishment, this paper deals with a specific way of organizing and managing tasks in plenary L2 classrooms — namely the round robin.

The paper describes the sequential position in which 327 hazel drive bear de free download robins are initiated and how this is talked and embodied into being by the participants as well as the design of the sownload that initiates the round robin activity.

Relevant to the initiation and further development of the round robin are the physical arrangement of the classroom and artefacts and graphic structures that are used not only as mediating tools in the supposed learning relevant activity, but also as structurally relevant features to organize the ongoing interaction, in which these activities emerge. International Journal of Bilingual Education and Bilingualism.

Olcay Sert. Maurice Nevile. Emilee Moore. Lynda Chubak. Chris Leyland. Kristian Mortensen. Gitte Rasmussen. Journal of International and Intercultural Communication. Yusuke Arano. Mariana Lazzaro Salazar. Unpublished Phd diessertation. University of Southern …. Preisler, A. Fabricius, H. Haberland, S.

Risage Eds. The consequences of mobility: Linguistic and Sociocultural Contact Zones pp. Marta Gonzalez-Lloret. Michael Handford. Multilingualism at work: from policies to practices …. Birgit Apfelbaum.

Mie F Nielsen. Zhu Hua. Arja Piirainen-Marsh. Lenore Manderson. Karen Grainger. Georges Luedi. Bal Krishna Sharma. Paul Seedhouse. Cade Bushnell. Anna CharalambidouKristina Ganchenko. Ifigenia Papageorgiou. Jason Turowetz. 327 hazel drive bear de free download Maheux-Pelletier. Rue Burch. Log in with Facebook Log in with Google. Remember me on this computer. Enter the email address you signed up with and gazel email you a reset link. Need an account? Click here to sign up. Download Free PDF.

Identities at odds: embedded and implicit language policing in the internationalized workplace. Abstract This study offers an interaction analytic account of how linguistic identities in internationalized workplaces in Denmark are indexed against members’ institutional positions in particular interactional contexts.

Related Papers. Journal of Pragmatics 62 Moving into interaction – embodied practices for initiating interactions ссылка на продолжение a help desk. Moving into interaction: Social practices for initiating encounters at a help desk. Embodying the institution: Object manipulation in developing interaction in study counselling meetings. Conversation Analysis for Intercultural Doenload. Symposium proceedings: Challenges and new directions in the micro-analysis of social interaction.

Introduction: A body of resources – CA studies of social conduct. Language and Intercultural Communication, Vol. Where language policy may not be explicitly articulated between members, it is still embedded in how participants micro- manage their interactions and implicit in how members display orientations to deviance, in the case of encountering others in the workplace whose language repertoires or preferences do not meet with expectation pertaining to the institutional position they hold.

Het onderzoek keek naar hoe verschillende taal identiteiten vergeleken werden met werknemers’ 327 hazel drive bear de free download functies, tijdens werkactiviteiten uitgevoerd samen met anderen. Keywords: linguistic identity; language policy; language choice; institutional identity; internationalization Introduction Workplaces around the world have increasingly come to be constituted as communities of transnationally mobile staff and clientele, and the resulting cultural and linguistic diversity to which this gives rise.

Hazel language scenarios Mortensen, as part and parcel of their ongoing daily workplace activities e. This in turn requires members to remain sensitive to a shifting bricolage of linguistic doqnload Gafaranga, encountered at any given moment as they go about their work-related activities, in order to be able http://replace.me/24652.txt respond appropriately, effectively and efficiently to each linguistic scenario as it arises.

The paper will argue for greater attention to be paid to the actual language-political practices in international workplace settings, as an entry point into developing a more nuanced understanding of the practices through which professional identities are brought about, affirmed and contested, and the linguistic considerations that are implicated in this.

This посмотреть еще complement research strands that investigate language policy, ideology and attitudes through a focus on official documentation or by drawing on qualitative research methods such as focus groups and interviews.

A growing number of institutions have moved to adopt formal policies pertaining dowload language practices — including that at the level of language choice — in the workplace e. Such explicit language policing may be introduced to respond to the changing demands that result from increased bearr, including the internationalized make-up of a particular institutional 327 hazel drive bear de free download, be it, for example, a company operating across borders or with greater numbers of migrant professionals, foreign-based clients or partners in other parts of the world, at popular tourist attractions or at particular institutional programmes within tertiary-level education.

However, such language-policy strategies may not apply, or be appropriate, fre all settings within a workplace community, hzael indeed reach all relevant parties. Furthermore, individual members may also hold entrenched ideological positions of their own pertaining to the relative value of the use of particular languages within a setting or to language requirements relating to institutional positions within a particular workforce.

Hence, backroom language policies may not be implemented or adhered to across all settings within a workplace community, and this necessitates members to remain prescient to the dynamics of such transient multilingual settings Goebel, In linguistically dynamic environments where language choice is then not predeter- mined by formal institutional policy, e.

Here, where language policy may not be explicitly discussed between members, it is still embedded in how participants micro-manage their Downloaded by [Roskilde Universitetsbibliotek], [Dr Spencer Hazel] at 23 January interactions. For example, Mortensen shows how locally established norms for language choice within student project groups are evidenced in how the members orient to the appropriateness of one or other language for engaging in particular activities, such as on-task or off-task talk.

Elsewhere, dde encounters where participants have no prior experience of interacting with one another, participants must also work together to alight upon the medium which best suits the parties involved and the institutionally oriented activities in which they are engaged Heller, ; Torras, Social science has occasioned a number of lines of investigation characterized by a focus on situated social action and interaction observed in their natural everyday habitats. The methodological perspective applied in the current study has its origins in the American sociological approach to language and social interaction, known as Ethno- methodology Garfinkel, ; henceforth EM.

In EM, the study of human sociality is premised on an understanding that there are methods of which members of a society avail themselves in their understanding, production and navigation of their social world.

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