Visual Experiences during Paralysis

Rationale: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one’s internal visual model and are the subject of this report. Methods: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. Results: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. Conclusion: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence

Visual Experiences during Paralysis

Rationale: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one’s internal visual model and are the subject of this report. Methods: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. Results: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. Conclusion: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence

The Naturalistic Flight Deck System: An Integrated System Concept for Improved Single-Pilot Operations

This paper reviews current and emerging operational experiences, technologies, and human-machine interaction theories to develop an integrated flight system concept designed to increase the safety, reliability, and performance of single-pilot operations in an increasingly accommodating but stringent national airspace system. This concept, know as the Naturalistic Flight Deck (NFD), uses a form of human-centered automation known as complementary-automation (or complemation) to structure the relationship between the human operator and the aircraft as independent, collaborative agents having complimentary capabilities. The human provides commonsense knowledge, general intelligence, and creative thinking, while the machine contributes specialized intelligence and control, extreme vigilance, resistance to fatigue, and encyclopedic memory. To support the development of the NFD, an initial Concept of Operations has been created and selected normal and non-normal scenarios are presented in this document

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

Objectives: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. Methods: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. Results: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. Conclusions: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost

Association between promoter -1607 polymorphism of MMP1 and Lumbar Disc Disease in Southern Chinese

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D), the -1607 promoter polymorphism, of the <it>MMP1 </it>gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD.</p> <p>Methods</p> <p>Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom^®platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test.</p> <p>Results</p> <p>Our results showed substantial evidence of association between -1607 promoter polymorphism of <it>MMP1 </it>and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04–1.90) while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01–2.24). Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033–2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029–2.029). Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele.</p> <p>Conclusion</p> <p>We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of <it>MMP1 </it>are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.</p

Dynamic T cell migration program provides resident memory within intestinal epithelium

Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation

The study of atmospheric ice-nucleating particles via microfluidically generated droplets

Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies