Vertical flight training: An overview of training and flight simulator technology with emphasis on rotary-wing requirements

The principal purpose of this publication is to provide a broad overview of the technology that is relevant to the design of aviation training systems and of the techniques applicable to the development, use, and evaluation of those systems. The issues addressed in our 11 chapters are, for the most part, those that would be expected to surface in any informed discussion of the major characterizing elements of aviation training systems. Indeed, many of the same facets of vertical-flight training discussed were recognized and, to some extent, dealt with at the 1991 NASA/FAA Helicopter Simulator Workshop. These generic topics are essential to a sound understanding of training and training systems, and they quite properly form the basis of any attempt to systematize the development and evaluation of more effective, more efficient, more productive, and more economical approaches to aircrew training. Individual chapters address the following topics: an overview of the vertical flight industry: the source of training requirements; training and training schools: meeting current requirements; training systems design and development; transfer of training and cost-effectiveness; the military quest for flight training effectiveness; alternative training systems; training device manufacturing; simulator aero model implementation; simulation validation in the frequency domain; cockpit motion in helicopter simulation; and visual space perception in flight simulators

Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease

Aims: Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's disease (AD) patients, but are associated with multiple side effects and only 20–40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of administration of a single dose of galantamine on central nervous system (CNS) functioning in mild to moderate AD patients and its potential to predict long-term treatment response. Methods: This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their minimental state examination (MMSE), neuropsychiatric inventory (NPI) and disability assessment in dementia (DAD) scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. Results: A single dose of galantamine significantly reduced saccadic reaction time (−0.0099; 95% CI = −0.0195, −0.0003; P =.0430), absolute frontal EEG parameters in alpha (−14.9; 95% CI = −21.0, −8.3; P =.0002), beta (−12.6; 95% CI = −19.4, −5.3; P =.0019) and theta (−17.9; 95% CI = −25.0, −10.0; P =.0001) frequencies. Relative frontal (−1.669; 95% CI = −2.999, −0.339; P =.0156) and occipital (−1.856; 95% CI = −3.339, −0.372; P =.0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95% CI = 0.158, 2.475; P =.0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (−20.4; 95% CI = −31.6, −7.47; P =.0046), beta (−15.7; 95% CI = −28.3, −0.93; P =.0390) and theta (−25.9; 95% CI = −38.4, −10.9; P =.0024) EEG parameters and of relative frontal theta power (−3.27%; 95% CI = −5.96, −0.58; P =.0187) on EEG significantly distinguished responders (n = 11) from non-responders (n = 32) after 6 months. Conclusions: This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment

Predictors of treatment response in a lupus nephritis population: lessons from the Aspreva Lupus Management Study (ALMS) trial

Objectives: To identify predictors of overall lupus and lupus nephritis (LN) responses in patients with LN. Methods: Data from the Aspreva Lupus Management Study (ALMS) trial cohort was used to identify baseline predictors of response at 6 months. Endpoints were major clinical response (MCR), improvement, complete renal response (CRR) and partial renal response (PRR). Univariate and multivariate logistic regressions with least absolute shrinkage and selection operator (LASSO) and cross-validation in randomly split samples were utilised. Predictors were ranked by the percentage of times selected by LASSO and prediction performance was assessed by the area under the receiver operating characteristics (AUROC) curve. Results: We studied 370 patients in the ALMS induction trial. Improvement at 6 months was associated with older age (OR=1.03 (95% CI: 1.01 to 1.05) per year), normal haemoglobin (1.85 (1.16 to 2.95) vs low haemoglobin), active lupus (British Isles Lupus Assessment Group A or B) in haematological and mucocutaneous domains (0.61 (0.39 to 0.97) and 0.50 (0.31 to 0.81)), baseline damage (SDI>1 vs =0) (0.38 (0.16 to 0.91)) and 24-hour urine protein (0.63 (0.50 to 0.80)). LN duration 2–4 years (0.43 (0.19 to 0.97) vs <1 year) and 24-hour urine protein (0.63 (0.45 to 0.89)) were negative predictors of CRR. LN duration 2–4 years (0.45 (0.24 to 0.83) vs <1 year) negatively predicted PRR. The AUROCs of models for improvement, CRR and PRR were 0.56, 0.55 and 0.51 respectively. Conclusions: Baseline variables predicted 6-month outcomes in patients with SLE. While the modest performance of models emphasises the need for new biomarkers to advance this field, the factors identified can help identify those patients who may require novel treatment strategies

Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort

BackgroundWe aimed to identify factors associated with a significant reduction in SLE disease activity over 12&nbsp;months assessed by the BILAG Index.MethodsIn an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12&nbsp;months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5&nbsp;mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models.Results'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use.ConclusionBaseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates