3,889 research outputs found
The Validity of a Brief Vestibular Disorientation Test in Screening Pilot Trainees
Validity of brief vestibular disorientation test in screening pilot trainee
Cross-validation of a brief vestibular disorientation test administered by a variety of personnel
Cross validation of brief vestibular disorientation test during pilot training administered by variety of personne
Plankton dynamics on the outer southeastern U.S. continental shelf. Part II: A time-dependent biological model
A system of ten coupled ordinary differential equations was developed to investigate the time-dependent behavior of phytoplankton and copepod populations associated with frontal eddy and bottom intrusion upwelling features on the outer southeastern U.S. continental shelf. Model equations describe the interactions of nitrate, ammonium, two phytoplankton size fractions (\u3e10 μm and \u3c10 μm), five copepod categories that represent the developmental stages of a population, and a detrital pool. Formulations for the biological processes are based primarily upon data obtained from laboratory and field experiments for southeastern U.S. continental shelf plankton populations. Time series of nutrient and plankton distributions obtained from GABEX II provide verification of model results. The simulated time dependent distributions for bottom intrusions show a phytoplankton maximum occurring approximately eight days after the nitrate maximum, and the copepod biomass peaks within eight to nine days after the phytoplankton. Frontal eddy simulations show the same succession except that the short time scale of these events precludes the development of large copepod blooms. To obtain the correct relative abundance of the two phytoplankton size fractions in the bottom intrusion simulations it was necessary to increase the cell death rate of the small (\u3c10 μm) cell size fraction relative to the large cells (.15 d–1 vs. .1 d–1). The additional loss from the small cells may represent a transfer to a zooplankton or microzooplankton grazer that is not included in the model. The depth-averaged (20 to 40 m) carbon production calculated from the bottom intrusion simulation was approximately 4 mgC m–2d–1 which agrees with production values measured for bottom intrusions. Model simulations indicate that temperature is a potentially important factor in determining the trophic structure in bottom intrusions. Also the role of frequency of nutrient input, fecal pellet remineralization and phytoplankton growth coefficient in determining the biological distributions in bottom intrusions were evaluated with the model
Neurons in the dorsomedial hypothalamus promote, prolong, and deepen torpor in the mouse
Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular, projections from the preoptic area of the hypothalamus to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity-dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence that the preoptic area of the hypothalamus and the DMH form part of a circuit within the mouse hypothalamus that controls entry into daily torpor. SIGNIFICANCE STATEMENT Daily heterotherms, such as mice, use torpor to cope with environments in which the supply of metabolic fuel is not sufficient for the maintenance of normothermia. Daily torpor involves reductions in body temperature, as well as active suppression of heart rate and metabolism. How the CNS controls this profound deviation from normal homeostasis is not known, but a projection from the preoptic area to the dorsomedial hypothalamus has recently been implicated. We demonstrate that the dorsomedial hypothalamus contains neurons that are active during torpor. Activity in these neurons promotes torpor entry and maintenance, but their activation alone does not appear to be sufficient for torpor entry
Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials
PURPOSE:
Interleukin-6 (IL-6) levels discriminate between patients with mild and severe COVID-19, making IL-6 inhibition an attractive therapeutic strategy. We conducted a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of randomized-controlled trials to ascertain the benefit of IL-6 blockade with tocilizumab for COVID-19.
METHODS:
We included randomized-controlled trials (RCTs) allocating patients with COVID-19 to tocilizumab. Our control group included standard care or placebo. Trials co-administering other pharmacological interventions for COVID-19 were not excluded. Primary outcome was 28–30 day mortality. Secondary outcomes included progression-to-severe disease defined as need for mechanical ventilation, intensive-care unit (ICU) admission, or a composite.
RESULTS: We identified 10 RCTs using tocilizumab, 9 of which reported primary outcome data (mortality), recruiting 6493 patients with 3358 (52.2%) allocated to tocilizumab. Tocilizumab may be associated with an improvement in mortality (24.4% vs. 29.0%; OR 0.87 [0.74–1.01]; p = 0.07; I2 = 10%; TSA adjusted CI 0.66–1.14). Meta-regression suggested a relationship between treatment effect and mortality risk, with benefit at higher levels of risk (logOR vs %risk beta = −0.018 [−0.037 to −0.002]; p = 0.07). Tocilizumab did reduce the need for mechanical ventilation and was associated with a benefit in the composite secondary outcome but did not reduce ICU admission.
CONCLUSIONS:
For hospitalized COVID-19 patients, there is some evidence that tocilizumab use may be associated with a short-term mortality benefit, but further high-quality data are required. Its benefits may also lie in reducing the need for mechanical ventilation
Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19—A retrospective cohort study
COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor monoclonal antibodies are associated with heterogenous treatment effects between male and female patients. We conducted a retrospective cohort study assessing the interaction between biological sex and anti-IL-6 receptor antibody treatment with respect to hospital mortality or progression of respiratory failure. We used a Cox proportional hazards regression model to adjust for age, ethnicity, steroid use, baseline C-reactive protein, and COVID-19 variant. We included 1274 patients, of which 58% were male and 15% received anti-IL-6 receptor antibodies. There was a significant interaction between sex and anti-IL-6 receptor antibody use on progression to respiratory failure or death (p = 0.05). For patients who did not receive anti-IL-6 receptor antibodies, the risk of death was slightly higher in males (HR = 1.13 (0.72–1.79)), whereas in patients who did receive anti-IL-6 receptor antibodies, the risk was lower in males (HR = 0.65 (0.32–1.33)). There was a heterogenous treatment effect with anti-IL-6 receptor antibodies between males and females; with anti-IL-6 receptor antibody use having a greater benefit in preventing progression to respiratory failure or death in males (p = 0.05)
Generating natural language specifications from UML class diagrams
Early phases of software development are known to be problematic, difficult to manage and errors occurring during these phases are expensive to correct. Many systems have been developed to aid the transition from informal Natural Language requirements to semistructured or formal specifications. Furthermore, consistency checking is seen by many software engineers as the solution to reduce the number of errors occurring during the software development life cycle and allow early verification and validation of software systems. However, this is confined to the models developed during analysis and design and fails to include the early Natural Language requirements. This excludes proper user involvement and creates a gap between the original requirements and the updated and modified models and implementations of the system. To improve this process, we propose a system that generates Natural Language specifications from UML class diagrams. We first investigate the variation of the input language used in naming the components of a class diagram based on the study of a large number of examples from the literature and then develop rules for removing ambiguities in the subset of Natural Language used within UML. We use WordNet,a linguistic ontology, to disambiguate the lexical structures of the UML string names and generate semantically sound sentences. Our system is developed in Java and is tested on an independent though academic case study
Measuring Interaction Design before Building the System: a Model-Based Approach
Early prototyping of user interfaces is an established good practice in interactive system development. However, prototypes cover only some usage scenarios, and questions dealing with number of required steps, possible interaction paths or impact of possible user errors can be answered only for the specific scenarios and only after tedious manual inspection. We present a tool (MIGTool) that transforms models of the behavior of a user interface into a graph, upon which usage scenarios can be easily specified, and used by MIGTool to compute possible interaction paths. Metrics based on possible paths, with or without user navigation errors, can then be computed. For example, when analyzing four mail applications, we show that Gmail has 3 times more shortest routes, has twice more routes that include a single user error, has routes with 13\ufewer steps, but has also optimal routes with the smallest probability to be chosen. Without MIGTool, this kind of analysis could only be done after building some prototype of the system, and then only for specific scenarios by manually tracing user actions and relative changes to the screens. With MIGTool the exploration of suitability of a design with respect to different scenarios, or comparison of different design alternatives against a single scenario, can be done with just a partial specification of the user interface behavior. This is made possible by the ability to associate scenarios steps to required user actions as defined in the model, by an efficient strategy to identify complete execution traces that users can follow, and by computing a range of diverse metrics on these results
Convalescent plasma for COVID-19: a meta-analysis, trial sequential analysis, and meta-regression
Background:
SARS-CoV-2-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression. /
Objective:
We performed a systematic review, meta-analysis, trials sequential analysis (TSA) and meta-regression of randomized control trials (RCTs) to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30-day mortality. Secondary outcomes included need for mechanical ventilation and intensive care (ICU) admission. /
Data sources:
PubMed, Embase, MedRxiv, and the Cochrane library on 2nd July 2021. /
Results:
Seventeen RCTs were identified recruiting 15,587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs. 25.5%; OR 0.94 (0.85 – 1.04); p = 0.23; I2 = 4%; TSA adjusted CI 0.84 – 1.05), or reduction in need for mechanical ventilation (15.7% vs. 15.4%; OR 1.01 [0.92 – 1.11]; p = 0.82; I2 = 0%; TSA adjusted CI 0.91 – 1.13), or ICU admission (22.4% vs. 16.7%; OR 0.80 (0.21 – 3.09); p = 0.75; I2 = 63%; TSA adjusted CI 0.0 – 196.05). Meta-regression did not reveal any association with titre of convalescent plasma, timing of administration, nor risk of death and treatment effect (p>0.05). Risk of bias was high in most studies. /
Conclusions:
In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.
PROSPERO registration
CRD42021234201
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