Hemispheric asymmetry in the maturation of the extra striate checkerboard onset evoked potential

Recently we have shown that the single positive deflection in the checkerboard onset evoked potential (EP) of young children of striate origin develops into a negative-positive complex. However, also an early positive peak becomes apparent in the checkerboard onset EP. To determine the origin and development of the activity underlying this early positive deflection we studied the checkerboard onset EPs in children of 9¿16 years of age. It was found that for the children in this age group two different dipole sources are responsible for the activity underlying the pattern onset EP. One of the dipoles corresponds to the activity generated in the striate cortex, whereas a second dipole of extrastriate origin is responsible for the appearance of the early positive deflection. This extrastriate activity shows hemispheric asymmetry, i.e. the strength of the right hemispheric extrastriate source exceeds the strength of the left hemispheric source. These results are in accordance with histological studies of Conel (1939¿1963) [The postnatal development of the human cerebral cortex (Vols 1¿8). Cambridge, Mass.: Harvard Univ. Press] which show that the maturation of the extrastriate areas of the left hemisphere is delayed with respect to the right hemisphere

Comparing Petri Net and Activity Diagram Variants for Workflow Modelling:A Quest for Reactive Petri Nets

Petri net variants are widely used as a workflow modelling technique. Recently, UMLa ctivity diagrams have been used for the same purpose, even though the syntax and semantics of activity diagrams has not been yet fully worked out. Nevertheless, activity diagrams seem very similar to Petri nets and on the surface, one may think that they are variants of each other. To substantiate or deny this claim, we need to formalise the intended semantics of activity diagrams and then compare this with various Petri net semantics. In previous papers we have defined two formal semantics for UMLact ivity diagrams that are intended for workflow modelling. In this paper, we discuss the design choices that underlie these two semantics and investigate whether these design choices can be met in low-level and high-level Petri net semantics. We argue that the main difference between the Petri net semantics and our semantics of UML act ivity diagrams is that the Petri net semantics models resource usage of closed, active systems that are non-reactive, whereas our semantics of UMLact ivity diagrams models open, reactive systems. Since workflow systems are open, reactive systems, we conclude that Petri nets cannot model workflows accurately, unless they are extended with a syntax and semantics for reactivity

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Source localization of EEG versus MEG: Emperical comparison using visually evoked responses and theoretical considerations

Theoretically, the information we can obtain about the functional localization of a source of brain activity from the scalp, for instance evoked by a sensory stimulus, is the same whether one uses EEG or MEG recordings. However, the nature of the sources and, especially of the volume conductor, poses constraints such that appreciable differences between both types of data may exist. We present here empirical and theoretical data that illustrate which are the main constraints and to what extent they may affect electric potential and magnetic field maps. The empirical data consists of visual evoked potential and magnetic fields to the appearance of a checkerboard pattern (half-visual field stimulation). The concept of equivalent dipole is presented and its limitations are discussed. It is considered that the concept of equivalent dipole (ED) yields only an approximate description of the activity of a patch of cortex. A main difference between EEG and MEG recordings is the fact that radially oriented dipoles can hardly be seen in the MEG in contrast with the EEG. Accordingly, a weak tangential dipole component is difficult to distinguish in the EEG if a strong radial component is also present. However, a combination of both methods can give useful complementary information in such cases. A factor that influences largely such differences is the model of volume conductor used. A four concentric spheres model, as commonly used for solving the inverse problem of source localization, causes appreciable errors when EEG data are used but much less in case of the MEG. The use of a model consisting of eccentric spheres fitting the four compartments, brain, CSF, skull and scalp, provides a better approximation of the real geometry of the head and allows to obtain comparable results for visual evoked potentials and magnetic fields. It is emphasized that for precise localization of EDs, especially based on EEG recordings, a realistic model of the different compartments of the head is necessary. The latter must be tailor made to a given subject using MRI-scans, in view of the large variability in head geometry between subjects