Particularities of Rotorcraft in Dealing with Advanced Controllers

Advanced nonlinear controllers are a desirable solution to rotorcraft flight control as they can solve the system high nonlinear dynamic behavior. However, conventional nonlinear controllers such as Nonlinear Dynamic Inversion (NDI) controller heavily rely on the availability of accurate model knowledge and this can be problematic for rotorcraft. Therefore, incremental control theory can solve the modelling errors sensitivity by relying on the information obtained from the sensors instead. The paper applied the Incremental Nonlinear Dynamic Inversion (INDI) controller to rotorcraft case. It will be demonstrated that, for rotorcraft, the incremental nonlinear controllers depend on the delays introduced in the controller by the rotor dynamics. To correct this behaviour, residualization and synchronization methods need to be applied accordingly in order to remove the effects of rotor flapping (disctilt) dynamics from the controller. These particularities of rotorcraft in dealing with advanced controllers shows that incremental nonlinear controllers can have relatively small stability robustness margin and careful controller design is needed in order to account properly for rotorcraft time delays and unmodelled dynamics

ROTORCRAFT-PILOT COUPLINGS: ANALYSIS AND DETECTION IN A SAFETY ENHANCEMENT FRAMEWORK

Nowadays, the complexity of high speed civil transport and highly-augmented rotorcraft, has led to an increase in the chances of encountering unwanted unstable phenomena, such as the so called Aircraft/Rotorcraft-Pilot Couplings (A/RPCs) or Pilot-Induced Oscillations (PIOs), whose unpredictability has given rise to a serious problem concerning the safety of a mission. When talking about PIOs, McRuer defined them as "inadvertent, sustained aircraft oscillations which are a consequence of an abnormal joint enterprise between the aircraft and the pilot". However, A/RPCs, these undesirable events associated with the interaction between pilot and aircraft, have become diverse and more complex than those encountered in the past. At the moment, there are different methods available to prevent and detect Cat. I/II A/RPC, but particular interest has recently arisen in this topic for 2ight simulation applications as any enhancement of these tools in order to accurately and objectively predict, detect (in real-time) and alleviate RPCs will be greatly welcomed. One of the main questions to be answered through the efforts carried out within this work is related to the better detection in real-time of embedded tendencies to RPCs in modern aircraft. To answer this question, initially an assessment of the eZcacy of the Phase-Aggression Criterion (PAC), which has been designed a few years ago at the University of Liverpool, will be undertaken either: as a means of alerting the pilot to conditions likely to lead to the onset of a PIO; or, given that the time available for the pilot to counteract may be extremely limited, as a means to assist him/her in alleviating (automatically) the PIO condition itself. Preliminary results from 2ight simulation trials to explore how best to achieve this will be reported. Moreover, this work will report on the development of PAC boundaries for more highly augmented response types. Furthermore, as classified by McRuer, Cat. III PIO, which is nonlinear in essence, is the most complex one. However, the researches on Cat. III PIO are rare. This paper will reveal some elementary results of Cat. III PIO. Since there is no existing method used for predicting and detecting Cat. III PIO, this paper utilized the characteristics of PIO, such as the amplitude, the oscillation frequency and ultimate tendency of key aircraft response states to judge Cat. III PIO preliminarily. By using this elementary judgment of PIO, we studied the following factors: time delay of pilot input and helicopter main body, actuator position saturation, actuator rate limit and SCAS control authority in triggering PIO. Results show that PIO induced by actuator position saturation, actuator rate limit and SCAS control authority can be regarded as Cat. III PIO as the variation of these factors can be viewed as a kind of transition of effective controlled vehicle dynamics. These kinds of transition can cause a mismatch between the effective controlled vehicle dynamics and pilot control strategy, which is the main cause of Cat. III PIO

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Practices to Identify and Preclude Adverse Aircraft-and-Rotorcraft-Pilot Couplings – A Design Perspective

Understanding, predicting and supressing the inadvertent aircraft oscillations caused by Aircraft/Rotorcraft Pilot Couplings (A/RPC) is a challenging problem for designers. These are potential instabilities that arise from the effort of controlling aircraft with high response actuation systems. The present paper reviews, updates and discusses desirable practices to be used during the design process for unmasking A/RPC phenomena. These practices are stemming from the European Commission project ARISTOTEL Aircraft and Rotorcraft Pilot Couplings – Tools and Techniques for Alleviation and Detection (2010–2013) and are mainly related to aerodynamic and structural modelling of the aircraft/rotorcraft, pilot modelling and A/RPC prediction criteria. The paper proposes new methodologies for precluding adverse A/RPCs events taking into account the aeroelasticity of the structure and pilot biodynamic interaction. It is demonstrated that high-frequency accelerations due to structural elasticity cause negative effects on pilot control, since they lead to involuntary body and limb-manipulator system displacements and interfere with pilot's deliberate control activity (biodynamic interaction) and, finally, worsen handling quality ratings