Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study.

BACKGROUND: Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. METHODS: Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. FINDINGS: Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). INTERPRETATION: Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. FUNDING: Fonds NutsOhra.

Applying the proportionality principle to COVID-19 antibody testing.

As the COVID-19 pandemic continues to ravage the globe, many nations have started to relax stringent restrictions in an effort to restart the economy. While Member States of the European Union have approached reopening without the use of antibody testing for COVID-19, such testing may be central to a long-term, sustainable strategy for international travel, employment, and the allocation and monitoring of vaccines. As the use of antibody testing to dictate the enjoyment of individual freedom remains highly controversial, we describe its use in the context of three case studies (return to the workplace, travel and vaccination), applying the substantive legal balancing entailed in the proportionality principle. Differential treatment of individuals based on COVID-19 antibody test results can be justified through the proportionality principle, which offers a sound dividing line between a reasonable and legitimate response and an unjust and discriminatory response.

Evaluation and Classification of Physical and Psychological Stress in Firefighters using Heart Rate Variability.

Stress detection has a huge potential for disease prevention and management, and to improve the quality of life of people. Also, work safety can be improved if stress is timely and reliably detected. The availability of low-cost consumer wearable devices that monitor vital-signs, gives access to stress detection schemes. Heart rate variability (HRV), a stress-related vital-sign, was derived from wearable device data to reliably determine stress-levels. In order to build and train a deployable stress-detector, we collected labeled HRV data in controlled environments, where subjects were exposed to physical, psychological and combined stress. We then applied machine learning to separate and identify the different stress types and understand the relationship with HRV data. The resulting C5 decision tree model is capable of identifying the stress type with 88% accuracy, in a 1-minute time window. For the first time physical and psychological stress can be distinguished with a 1-minute time resolution from smoke-divers, firefighters, who enter high-risk environments to rescue people, and experience intense physical and psychological stress. To improve our model, we created an integrated system to acquire expert labels in real-time from firefighters during their training in a Rescue Maze. A next goal is to transfer the algorithms into generic systems for monitoring and coaching high-risk professionals to improve their stress resilience during training and reduce their risk in the field.

Multipartite Entanglement of a Two-Separable State.

We consider a six-partite, continuous-variable quantum state that we have effectively generated by the parametric down-conversion of a femtosecond frequency comb. We show that, though this state is two-separable, i.e., it does not exhibit "genuine entanglement," it is undoubtedly multipartite entangled. The consideration of not only the entanglement of individual mode decompositions, but also of combinations of those, solves the puzzle and exemplifies the importance of studying different categories of multipartite entanglement.

Full multipartite entanglement of frequency-comb Gaussian states.

An analysis is conducted of the multipartite entanglement for Gaussian states generated by the parametric down-conversion of a femtosecond frequency comb. Using a recently introduced method for constructing optimal entanglement criteria, a family of tests is formulated for mode decompositions that extends beyond the traditional bipartition analyses. A numerical optimization over this family is performed to achieve maximal significance of entanglement verification. For experimentally prepared 4-, 6-, and 10-mode states, full entanglement is certified for all of the 14, 202, and 115 974 possible nontrivial partitions, respectively.

Nitrogen transformations in a wetland receiving lagoon effluent: sequential model and implications for water reuse.

Constructed wetlands could be components of low-tech systems to treat and reuse wastewater in arid region. A key function of the wetland would be to provide additional N removal. To improve design criteria, a sequential model of nitrogen transformations (organic N --> ammonium: ammonium --> nitrate: nitrate --> nitrogen gas) was successfully calibrated and verified for a wetland in Kingman, Arizona. A sequential model has the ability to "recognize" species of nitrogen in the influent and predict species of nitrogen in the effluent. Model scenarios show that increasing nitrification rates in the summer and denitrification rates in the winter would improve nitrogen removal efficiencies. Several lines of evidence suggest that wintertime denitrification may be limited by carbon supply. Winter carbon supply could be augmented by routing a portion of the water through channels planted with dryland vegetation.

Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type.

Thirty-three patients with mild primary degenerative dementia according to DSM-III (MMS between 15 and 27) took part in a double-blind cross-over study of phosphatidylserine (Fidia, 300 mg/d) versus placebo. Both treatment phases lasted for 8 weeks with an 8 week washout phase in between and a 4 week washout phase before treatment phase one. Clinical global improvement ratings showed significantly more patients improving under BC-PS than under placebo during treatment phase one. The improvement carried over to the following wash-out and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. 16-channel EEG mapping findings indicated that the patients initially showed higher power values in all frequency bands (except alpha), when compared to a younger, healthy control group. BC-PS reduced the higher power values compared to placebo, shifting EEG power more towards the normal level.