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Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT.TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890).From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64).In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT.Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (pvs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups.Interpretation: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting.Funding: British Heart Foundation.

Although there are several robust theories of ‘thermodynamics’ operating very successfully over a range of different disciplines, for example, biology, chemistry, geoscience, quantum theory, astrophysics and numerous associated technologies, there are still no unifying foundations for this most important branch of science. Yet, most elementary thermodynamics is taught from an unjustifiable assumption of consistency and certainty. The current inconsistencies that permeate the science community’s thinking about ‘heat’ first appear at the time of Kelvin. This chapter traces some of the early attempts to formulate a theory of ‘heat’ and indicates a way in which we can improve our approach to the teaching of elementary thermodynamics by attempting to empathise with Kelvin’s perspective.

The paper presents experimental and theoretical investigation of the outflow of liquids from single-outlet vessels incorporating a vertical downcomer. In such vessels the liquid leaving through the outlet of the downcomer is replaced by another fluid, which enters the vessel-downcomer system through the same opening. Experimental results of the variation of the void fraction and pressure in the vessel with elapsed time are presented. It is shown that the flow is generally oscillatory, and the conditions required for the establishment of the fully developed oscillatory flow are reported. A theoretical model of the fully developed oscillatory flow is developed. The model describes well the frequency of the oscillatory flow and the variation of the gas void fraction in the vessel with elapsed time. The model somewhat overpredicts the amplitude of the pressure oscillations. Thermodynamic aspects of this flow are also considered.

An experimental and theoretical study recently investigated the transient processes that occur when hot liquid spray droplets are suddenly injected into air contained in a closed chamber [1]. The analysis gathered all important parameters governing droplet heat transfer in a single dimensionless group, denoted by K2. The work has been extended by redefining K2, and introducing a new dimensionless group KN2, and by using helium as the surrounding gas. The dimensionless group KN2 is, to a first approximation, independent of all parameters investigated in the present work, including the properties of the surrounding gas, and approximately equal to 0.12. The dimensionless group KN2 =0.12 should be used instead of the Nusselt number as the primary dimensionless group in analysing the heat transfer performance of spray injection nozzles in closed chambers.

There are many processes in engineering in which a physical parameter y normally varies linearly with another physical parameter x, but where, on occasion, a step change in the variation of parameter y may occur. A typical example of this phenomenon is the variation of the pressure drop along an obstructed straight pipe. It is the purpose of this paper to develop a direct method for determining this step change and to consider the implications.

This paper analyses the outflow of liquids from single-outlet vessels. In such vessels the liquid leaving the vessel through the outlet is replaced by another fluid, which enters the vessel through the same opening. A theoretical model is developed for the general case of gas—liquid systems. The model, based on a simplified description of the system, is derived from first principles, and contains one adjustable parameter. Irrespective of the numerical value of this parameter the model describes qualitatively the various phenomena observed experimentally, such as the linear variation between the large-scale gas void fraction in the vessel and the elapsed time. A correlation for the adjustable parameter is presented and its significance discussed. The model is in excellent agreement with the available experimental data on the variation of the large-scale gas void fraction in the vessel and the large-scale gas pressure in the vessel with elapsed time. The application of the model is also discussed.

This paper considers the oscillatory behaviour of liquids in single-outlet vessels, i.e. vessels in which the outflowing liquid is replaced by another fluid which enters the vessel through the same opening. A theoretical model is developed and an equation for the natural frequency of oscillations obtained. The model is in good agreement with the available experimental data. It is shown that the natural oscillations of the liquid govern the hydrodynamic processes involved.

This paper considers the influence of viscosity and circulation on the effect of vortices on the liquid outflow from open vessels. One of the simplest possible arrangements is investigated: an axisymmetric vertical cylindrical vessel with an outlet in its base with the vortex flow generated by supplying the liquid through pipes located at the perimeter of the vessel. It is shown that for low liquid levels in the vessel the vortex provides a hindrance to the flow, but that for high liquid levels it is the vortex flow which discharges more freely. It is also shown that the liquid level in the vessel is proportional to the liquid flowrate, with the constant of proportionality being a function of viscosity and initial circulation.

An investigation has been undertaken to examine the stability of a gas-liquid interface in a vertical cylindrical vessel subjected to a sinusoidal vertical motion. Experimental results indicate that there is a certain limiting critical frequency at which the gas-liquid interface becomes unstable, significant amounts of liquid are thrown vertically from the interface and the interface thus loses its coherent structure. Experimental data are compared with analytical solution based on the reduction of governing non-viscous equations to Mathieu equation, and good agreement between theory and experiment is found.

The complexity of implementing client/server architectures often relegates the most important element in an effective system—the user—to the back burner. Usability engineering, or user–centered design, maximizes the likelihood that users will find an application solution useful and effective while also reducing development cycle, costs, and failure risks.

This paper considers the outflow of a liquid from a single outlet vessel, i.e. a vessel in which the outflowing liquid is displaced by another fluid which enters the vessel through the same opening. The simplest possible arrangement is investigated: a sealed axisymmetric cylindrical vessel with an outlet in its base, in which water is displaced by air. It is shown experimentally that the average liquid discharge velocity is independent of the liquid level in the vessel and the shape of the outlet for the range of outlets employed; it increases weakly with both the diameter of the vessel and the diameter of the outlet.

To protect against accidents and their consequences, companies may take one of several courses of action. They can choose to do nothing, and live with an 'acceptable risk', or they may invest heavily in training, technology, preventive maintenance and damage limitation exercises. There are several courses of action in between these two, but at what point does a precaution become one too many?.

A model is developed for predicting the influence of the containing walls on heat transfer processes in stagnant beds of solid particles. The model describes the effect of the walls on the mean voidage of the bed and on the mean effective thermal conductivity of the bed. The theoretical predictions are compared with available experimental data.

An investigation has been made of air-water flow in Y-junctions, which are frequently used in industrial applications. The air-water flow is stratified in the sloping limbs approaching the junction and this paper examines the phenomena occurring at the junction and in the following freely discharging vertical pipe. It is shown that three flow regimes can exist in the vertical limb following the junction: freely-falling water, homogeneous flow of water and air, and flow of water with a small amount of residual air accompanied by the flooding of the junction. The flow regimes are described and predictions for transitions between them are developed.

One of the flow regimes occurring in horizontal two-phase flows is characterized by periodic large waves “surging” along the tube. This flow, called “slug” flow, has been frequently observed in low and high pressure gas liquid systems, but it has been noticed that slugging is absent in certain liquid-liquid two-phase systems. A method is developed giving the necessary conditions for the presence of slug flow. This method quantitatively explains the observed absence of slugging in certain liquid-liquid flows.

(1985). Management of Risk and Safety. Safety and Reliability: Vol. 5, Newsletter of the Safety and Reliability Society, pp. 11-18.

It has been shown previously (Gardner & Kubie 1976) that a two-liquid system provides a better analogue for investigating certain aspects of high pressure boiler tube hydrodynamics than air and water at atmospheric pressure. A study is presented here of the flow of n- butyl acetate and water, and iso-amyl alcohol and water in helical coils and the general conclusion is that strongly stratified conditions of either completely separated phases or of drops of one phase in the other exist until velocities are high enough to produce drops sufficiently fine to be dispersed by the turbulence. The critical condition for the breakdown of the separated phases to produce drops is quantitatively correlated with the mass flowrates needed to avoid low quality dryout in both high pressure water and high pressure freon helical boilers. Some evidence is available to support two criteria indicating that low quality dryout will not be observed for sufficiently low pressures in steam-water systems and, perhaps, for small enough bore tubes.

Measurements were made of the size distribution and maximum size of drops in liquid-liquid systems. The data on the maximum drop size, together with other data available in the literature, are assessed in the light of Hinze's [1] theory. It is shown that the dispersion of drops in a gravitational field transverse to the flow can be predicted using correlations for the terminal velocity and for the drop diffusivity.

An investigation has been made of steam-water flow in a vertical coplanar Y-junctions which are used, for example, in the condensate carrying pipework downstream of direct contact heat exchangers. The steam-water flow is stratified in the sloping limbs approaching the junction and this paper examines problems associated with the flooding of the junction. It is shown that at low water flowrates water falls freely through the junction, but as the water flowrate increases a condition is reached when the water starts to pile at the junction and the junction is said to be flooded. Further increase in the water flowrate causes the water level to rise within the sloping limbs approaching the junction. A simple analytical model is developed which describes reasonably well the flow phenomena observed.

An investigation has been made of aspects of steady state outflow of saturated water from horizontal cylindrical vessels with an outlet on their bottom surface. It is shown that there are two regimes of outflow, one governed by the design of the vessel and the other by the design of the outlet. Experimental data on the variation of the level in the vessel with the flowrate are presented, and it is shown that they are in reasonable agreement with the theoretical results applicable to the two flow regimes and the transition between them. Finally, equations governing the variation of the liquid level along the vessel are presented.

Two parameters of particle or droplet dynamics which are of importance in describing their behaviour in turbulent pipe flows are their settling velocity and eddy diffusivity. It is usually assumed that the settling velocity in turbulent flow is equal to that in still fluid and on the basis of this assumption the eddy diffusivity is usually determined experimentally from the distribution of droplets or particles in horizontal turbulent flow. Since the settling velocity has a strong influence on the resultant value of the eddy diffusivity, the influence of turbulence on settling velocity is investigated in this work. A simple stochastic model of settling in turbulent flow is developed and it is shown that a considerable retardation of still fluid settling velocity is possible for a wide range of conditions.

The influence of gas bubbles on heat transfer in gas fluidized beds has been investigated. A platinum wire has been used as a heat-transfer probe and the aggregative gas fluidized bed has been simplified by generating a single continuous stream of gas bubbles into an incipiently fluidized bed. It has been found that in the case of aggregative gas fluidized beds of small particles operating below the radiative temperature level, transient conduction into the emulsion phase is responsible for at least 90% of heat transfer and that the remainder is contributed by the superimposed gas convection. A theoretical model of the bubble induced heat transfer has been developed. Finally, experimental justification for the concept of the property boundary layer introduced in [2] is presented.

The mechanism of heat transfer at surfaces in fluidized beds is discussed and a variant of the penetration theory is developed in which the packet theory of heat transfer is modified to allow for, and describe quantitatively, property variations in the packet in the region of the surface. Property variations are described in terms of the voidage variations in the vicinity of a constraining surface which are modelled from simple geometrical considerations. The model of the heat-transfer process derived here shows good agreement with experimental data without recourse to any of the semi-empirical approximations that are features of the previous models.

An investigation has been made of flow phenomena associated with outflow from large horizontal cylindrical vessels with a vortex-free outlet on their bottom surface. This paper concentrates on the flow regimes and the variation of the level in the vessels with the flowrate. It is shown, both theoretically and experimentally, that there are two distinct regimes of outflow from the vessel, which are separated by a critical flowrate which is a strong function of the diameter of the outflow orifice. For the flowrates below the critical the level variation does not depend on the diameter of the outflow orifice, but the level variation depends strongly on it for the flowrates above the critical value. A model of transition between the flow regimes is also developed.

The influence of gas bubbles on heat transfer in two phase gas-liquid systems has been investigated. Platinum wires have been used as heat-transfer probes and the two phase flow has been simulated by generating a single continuous stream of discrete gas bubbles into a stationary liquid. The contribution of various modes of heat transfer has been determined. It has been found that transient conduction into the liquid is the predominant mode of the bubble induced heat transfer and is responsible for about 75 per cent of heat transfer. Convection contributes the remainder. A theoretical model of the bubble induced heat transfer based on the surface renewal and penetration theory has been developed.

A two-liquid system provides a better analogue for visualization purposes of high pressure boiler systems, where the density ratio is typically 4:1, than air and water at atmospheric pressure. A study is presented of the flow of isoamyl alcohol and water in sloping tubes and a stratified ribbon of alcohol is found, which is not seen with air and water, and this accounts for some corrosion failures in boilers. A critical condition is also encountered when the ribbon starts to be broken into drops and this quantitatively explains the occurrence of a minimum in the curve of burnout heat flux vs water velocity in steam-water systems from 11 to 18 MN/m 2 .

Plug check valves are frequently used in high pressure systems where parallel pump operations are envisaged, in order to prevent flow recirculation through the out-of-service pump. Serious operational problems are sometimes encountered with these valves during pump changeovers. Full equations of the dynamic behaviour of the plug check valves are derived and results are obtained for their performance in a typical power plant system. Criteria for the design of the plug check valves are also developed.

A model of axisymmetric liquid outflow from large vessels is developed and is used to explain aspects of flow for self-venting and choked outlets. It is shown that for flows with self-venting outlets the model relates the liquid level to the flow. It is also shown that for flow with choked outlets the model gives a conservative estimate for the minimum liquid level required to prevent drawdown of the supernatant phase. The results obtained are also compared with the experimental and theoretical work of previous investigators.

The distribution of voidage in the wall regions of randomly packed beds of uniform spheres is investigated. A general equation relating the local voidage to the distribution of the spheres is derived and is combined with some simple observations about the bed to develop a model of particle packing near containing walls. The results of the analysis are in good agreement with available experimental data.