Editors' Review and Introduction: Learning Grammatical Structures: Developmental, Cross‐Species, and Computational Approaches

Human languages all have a grammar, that is, rules that determine how symbols in a language can be combined to create complex meaningful expressions. Despite decades of research, the evolutionary, developmental, cognitive, and computational bases of grammatical abilities are still not fully understood. “Artificial Grammar Learning” (AGL) studies provide important insights into how rules and structured sequences are learned, the relevance of these processes to language in humans, and whether the cognitive systems involved are shared with other animals. AGL tasks can be used to study how human adults, infants, animals, or machines learn artificial grammars of various sorts, consisting of rules defined typically over syllables, sounds, or visual items. In this introduction, we distill some lessons from the nine other papers in this special issue, which review the advances made from this growing body of literature. We provide a critical synthesis, identify the questions that remain open, and recognize the challenges that lie ahead. A key observation across the disciplines is that the limits of human, animal, and machine capabilities have yet to be found. Thus, this interdisciplinary area of research firmly rooted in the cognitive sciences has unearthed exciting new questions and venues for research, along the way fostering impactful collaborations between traditionally disconnected disciplines that are breaking scientific ground

Release of Soluble Receptors for Tumor Necrosis Factor in Clinical Sepsis and Experimental Endotoxemia

To assess the role of tumor necrosis factor (TNF) in the appearance of soluble TNF receptors (sTNFRs), 20 consecutive patients with a clinical diagnosis of sepsis were studied as were 7 chimpanzees after administration of endotoxin (4 ng/kg) with or without pentoxifylline. The patients had markedly elevated serum levels of sTNFR-p55 and sTNFR-p75 compared with healthy controls (P < .0001 for both receptors). The levels of both soluble receptors correlated with simultaneously measured immunoreactive TNF concentrations (p55: r = .63, P < .01; p75: r = .69, P < .001). In the chimpanzees, endotoxin induced subsequent rises in the serum concentrations ofTNF and sTNFRs. Although pentoxifylline reduced the TNF response to intravenous endotoxin to 20% (P < .05), the appearance of sTNFRs was only moderately inhibited (sTNFR-p55 to 79% on average, P < .05; sTNFR-p75 to 77%, P = .12). These results indicate that TNF either does not play an important role in the appearance of sTNFRs in systemic infection or that a small amount ofTNF remaining in the circulation after some bacterial challenges is sufficient to preserve the secretion of its soluble receptor

ОБМЕН СООБЩЕНИЯМИ В МИКС-СЕТЯХ

Рассмотрена идея Д.Чаума организации анонимной микс-сети с пересылкой сообщений через каскад миксов (передаточных узлов) и последовательным шифрованием всех промежуточных результатов. Описаны задачи, решаемые миксами в ходе обеспечения анонимности связи, обговариваются проблемы ее безопасности

Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians

Click to hear Dr Baglin's perspective on the role of the laboratory in treatment with new oral anticoagulants SUMMARY: One of the key benefits of the direct oral anticoagulants (DOACs) is that they do not require routine laboratory monitoring. Nevertheless, assessment of DOAC exposure and anticoagulant effects may become useful in various clinical scenarios. The five approved DOACs (apixaban, betrixaban, dabigatran etexilate, edoxaban and rivaroxaban) have different characteristics impacting assay selection and the interpretation of results. This article provides an updated overview on (i) which test to use (and their advantages and limitations), (ii) when to assay DOAC levels, (iii) how to interpret the results relating to bleeding risk, emergency situations and perioperative management, and (iv) what is the impact of DOACs on routine and specialized coagulation assays. Assays for anti-Xa or anti-IIa activity are the preferred methods when quantitative information is useful, although the situations in which to test for DOAC levels are still debated. Different reagent sensitivities and variabilities in laboratory calibrations impact assay results. International calibration standards for all specific tests for each DOAC are needed to reduce the inter-laboratory variability and allow inter-study comparisons. The impact of the DOACs on hemostasis testing may cause false-positive or false-negative results; however, these can be minimized by using specific assays and collecting blood samples at trough concentrations. Finally, prospective clinical trials are needed to validate the safety and efficacy of proposed laboratory thresholds in relation to clinical decisions. We offer recommendations on the tests to use for measuring DOACs and practical guidance on laboratory testing to help patient management and avoid diagnostic errors. ispartof: Journal of Thrombosis and Haemostasis vol:16 issue:2 pages:209-219 ispartof: location:England status: publishe

Remote Non-invasive Stereoscopic Imaging of Blood Vessels: First In-vivo Results of a New Multispectral Contrast Enhancement Technology

We describe a contactless optical technique selectively enhancing superficial blood vessels below variously pigmented intact human skin by combining images in different spectral bands. Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, simultaneously streamed Left (L) and Right (R) image data to a dual-processor PC. Both cameras captured color images within the visible range (VIS, 400–780 nm) and grey-scale images within the near infrared range (NIR, 910–920 nm) by sequentially switching between LED-array emission bands. Image-size-settings of 1280 × 1024 for VIS & 640 × 512 for NIR produced 12 cycles/s (1 cycle = 1 VIS L&R-pair + 1 NIR L&R-pair). Decreasing image-size-settings (640 × 512 for VIS and 320 × 256 for NIR) increased camera-speed to 25 cycles/s. Contrasts from below the tissue surface were algorithmically distinguished from surface shadows, reflections, etc. Thus blood vessels were selectively enhanced and back-projected into the stereoscopic VIS-color-image using either a 3D-display or conventional shutter glasses. As a first usability reconnaissance we applied this custom-built mobile stereoscopic camera for several clinical settings: • blood withdrawal; • vein inspection in dark skin; • vein detection through iodide; • varicose vein and nevi pigmentosum inspection. Our technique improves blood vessel visualization compared to the naked eye, and supports depth perception

Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy

Background - Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). Methods and Results - CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52±16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75±23 g at baseline to 68±22 and 58±19 g (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141±41 to 132±40 and 111±27 g (P<0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up (P=0.03). Conclusions - Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder

Analysis of blood coagulation in mice: pre-analytical conditions and evaluation of a home-made assay for thrombin-antithrombin complexes

BACKGROUND: The use of mouse models for the study of thrombotic disorders has gained increasing importance. Methods for measurement of coagulation activation in mice are, however, scarce. The primary aim of this study was to develop a specific mouse thrombin-antithrombin (TAT) ELISA for measurement of coagulation activation and to compare it with two commercially available assays for human TAT complexes. In addition, we aimed to improve methods for mouse plasma anticoagulation and preparation. METHODS AND RESULTS: First, for the measurement of TAT-complexes in plasma a mouse specific TAT-ELISA was developed using rabbit polyclonal antibodies raised against mouse thrombin and rat antithrombin, respectively. This ELISA detected an increase in TAT levels in a mouse model of endotoxemia. Two commercial human TAT ELISAs appeared to be less specific for mouse thrombin-rat antithrombin complexes. Second, to prevent clotting of mouse blood sodium citrate was either mixed with blood during collection in a syringe or was injected intravenously immediately prior to blood collection. Intravenous sodium citrate completely inhibited blood coagulation resulting in plasma with consistently low TAT levels. Sodium citrate mixed with blood during collection resulted in increased TAT levels in 4 out of 16 plasma samples. Third, heparinase was added to plasma samples after in vivo injection of different heparin doses to test its neutralizing effect. Heparinase neutralized up to a 20 U of heparin/mouse and resulted in accurate APTT and factor VIII determinations. CONCLUSION: These procedures and reagents for plasma preparation and coagulation testing will improve studies on thrombotic disorders in mice

Are we on the right track in DBS surgery for dystonic head tremor?:Polymyography is a promising answer

The clinical benefit of Deep Brain Stimulation (DBS) is associated with electrode positioning accuracy. Intraoperative assessment of clinical effect is therefore key. Evaluating this clinical effect in patients with dystonic head tremor, as opposed to limb tremor, is challenging because the head is fixed in a stereotactic frame. To clinically assess head tremor during surgery, surface electromyography (EMG) electrodes were bilaterally applied to the sternocleidomastoid and cervical paraspinal muscles. This case shows that intraoperative polymyography is an easy and useful tool to assess the clinical effect of DBS electrode positioning