Mismatch-based delayed thrombolysis: a meta-analysis

<p><b>Background and Purpose</b>: Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.</p> <p><b>Methods</b>: We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I2 (inconsistency), and L’Abbé plot.</p> <p><b>Results</b>: We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I2=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I2=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I2=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I2=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I2=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I2=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I2=0%).</p> <p><b>Conclusions</b>: Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.</p&gt

Multiple Phosphorylation of Rhodopsin and the In Vivo Chemistry Underlying Rod Photoreceptor Dark Adaptation

AbstractDark adaptation requires timely deactivation of phototransduction and efficient regeneration of visual pigment. No previous study has directly compared the kinetics of dark adaptation with rates of the various chemical reactions that influence it. To accomplish this, we developed a novel rapid-quench/mass spectrometry-based method to establish the initial kinetics and site specificity of light-stimulated rhodopsin phosphorylation in mouse retinas. We also measured phosphorylation and dephosphorylation, regeneration of rhodopsin, and reduction of all-trans retinal all under identical in vivo conditions. Dark adaptation was monitored by electroretinography. We found that rhodopsin is multiply phosphorylated and then dephosphorylated in an ordered fashion following exposure to light. Initially during dark adaptation, transduction activity wanes as multiple phosphates accumulate. Thereafter, full recovery of photosensitivity coincides with regeneration and dephosphorylation of rhodopsin

An expert assessment on playspace designs and thermal environments in a Canadian context

Playgrounds are a hub for child play and concerns that may impact children\u27s play there may hinder their health and well-being. Extreme temperatures can increase risks in children of sunstroke, burns from playground surfaces, and exposure to ultraviolet radiation. Despite health risks from extreme heat to children, existing playground design standards around the world, including in Canada, make little-to-no mention of how to design playgrounds for thermal comfort, particularly in summer. To help fill this gap in the Canadian context, several organizations collaborated to develop guidance for thermally comfortable playgrounds in Canada. As part of this project, an online survey was administered to 55 experts with diverse professional backgrounds, largely from Canada and the United States, to determine how thermal comfort is viewed in playground design and safety. Survey results showed agreement among experts that thermal comfort receives low or no priority in playground design but should be prioritized or considered alongside other safety factors in relevant playground safety guidelines and standards. The results of this survey not only helped inform the 2020 publication of a Thermal Comfort annex to the CSA Group\u27s Children\u27s playgrounds and equipment standard (CAN/CSA Z614) but could also help inform future research and practice globally

Next-generation carrier screening

Purpose: Carrier screening for recessive Mendelian disorders traditionally employs focused genotyping to interrogate limited sets of mutations most prevalent in specific ethnic groups. We sought to develop a next-generation DNA sequencing–based workflow to enable analysis of a more comprehensive set of disease-causing mutations. Methods: We utilized molecular inversion probes to capture the protein-coding regions of 15 genes from genomic DNA isolated from whole blood and sequenced those regions using the Illumina HiSeq 2000 (Illumina, San Diego, CA). To assess the quality of the resulting data, we measured both the fraction of the targeted region yielding high-quality genotype calls, and the sensitivity and specificity of those calls by comparison with conventional Sanger sequencing across hundreds of samples. Finally, to improve the overall accuracy for detecting insertions and deletions, we introduce a novel assembly-based approach that substantially increases sensitivity without reducing specificity. Results: We generated high-quality sequence for at least 99.8% of targeted base pairs in samples derived from blood and achieved high concordance with Sanger sequencing (sensitivity >99.9%, specificity >99.999%). Our novel algorithm is capable of detecting insertions and deletions inaccessible by current methods. Conclusion: Our next-generation DNA sequencing–based approach yields the accuracy and completeness necessary for a carrier screening test

Innovations in air sampling to detect plant pathogens

Many innovations in the development and use of air sampling devices have occurred in plant pathology since the first description of the Hirst spore trap. These include improvements in capture efficiency at relatively high air-volume collection rates, methods to enhance the ease of sample processing with downstream diagnostic methods and even full automation of sampling, diagnosis and wireless reporting of results. Other innovations have been to mount air samplers on mobile platforms such as UAVs and ground vehicles to allow sampling at different altitudes and locations in a short space of time to identify potential sources and population structure. Geographical Information Systems and the application to a network of samplers can allow a greater prediction of airborne inoculum and dispersal dynamics. This field of technology is now developing quickly as novel diagnostic methods allow increasingly rapid and accurate quantifications of airborne species and genetic traits. Sampling and interpretation of results, particularly action-thresholds, is improved by understanding components of air dispersal and dilution processes and can add greater precision in the application of crop protection products as part of integrated pest and disease management decisions. The applications of air samplers are likely to increase, with much greater adoption by growers or industry support workers to aid in crop protection decisions. The same devices are likely to improve information available for detection of allergens causing hay fever and asthma or provide valuable metadata for regional plant disease dynamics

Target company cross-border effects in acquisitions into the UK

We analyse the abnormal returns to target shareholders in crossborder and domestic acquisitions of UK companies. The crossborder effect during the bid month is small (0.84%), although crossborder targets gain significantly more than domestic targets during the months surrounding the bid. We find no evidence for the level of abnormal returns in crossborder acquisitions to be associated with market access or exchange rate effects, and only limited support for an international diversification effect. However, the crossborder effect appears to be associated with significant payment effects, and there is no significant residual crossborder effect once various bid characteristics are controlled for

Foreign policy and political possibility

This article explores the relationship between foreign policy and political possibility in two parts. First, the relationship between foreign policy and political possibility is theorized around three analytical moments: political possibility is linked to the framing of conceivable, communicable and coercive foreign policy. Second, this framework is developed and demonstrated through a brief analysis of Coalition foreign policy in the War on Terror, considering American, British and Australian foreign policy between 2001 and 2003. This analysis dissects distinct and divergent Coalition foreign policies through a linked three-part conceptualization of political possibility. It enables an understanding of how the War on Terror was rendered possible through the construction of foreign policy in thinkable, resonant and ultimately dominant terms. The article concludes by looking to the wider analytical applicability of this particular theorization of the relationship between foreign policy and political possibility

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Fractal iso-contours of passive scalar in smooth random flows

We consider a passive scalar field under the action of pumping, diffusion and advection by a smooth flow with a Lagrangian chaos. We present theoretical arguments showing that scalar statistics is not conformal invariant and formulate new effective semi-analytic algorithm to model the scalar turbulence. We then carry massive numerics of passive scalar turbulence with the focus on the statistics of nodal lines. The distribution of contours over sizes and perimeters is shown to depend neither on the flow realization nor on the resolution (diffusion) scale $r_d$ for scales exceeding $r_d$. The scalar isolines are found fractal/smooth at the scales larger/smaller than the pumping scale $L$. We characterize the statistics of bending of a long isoline by the driving function of the L\"owner map, show that it behaves like diffusion with the diffusivity independent of resolution yet, most surprisingly, dependent on the velocity realization and the time of scalar evolution