Framework for state and unknown input estimation of linear time-varying systems

The design of unknown-input decoupled observers and filters requires the assumption of an existence condition in the literature. This paper addresses an unknown input filtering problem where the existence condition is not satisfied. Instead of designing a traditional unknown input decoupled filter, a Double-Model Adaptive Estimation approach is extended to solve the unknown input filtering problem. It is proved that the state and the unknown inputs can be estimated and decoupled using the extended Double-Model Adaptive Estimation approach without satisfying the existence condition. Numerical examples are presented in which the performance of the proposed approach is compared to methods from literature.Comment: This paper has been accepted by Automatica. It considers unknown input estimation or fault and disturbances estimation. Existing approaches considers the case where the effects of fault and disturbance can be decoupled. In our paper, we consider the case where the effects of fault and disturbance are coupled. This approach can be easily extended to nonlinear system

Validity of the self-administered comorbidity questionnaire in patients with inflammatory bowel disease

Background: The International Consortium for Health Outcomes Measurement has selected the self-administered comorbidity questionnaire (SCQ) to adjust case-mix when comparing outcomes of inflammatory bowel disease (IBD) treatment between healthcare providers. However, the SCQ has not been validated for use in IBD patients. Objectives: We assessed the validity of the SCQ for measuring comorbidities in IBD patients. Design: Cohort study. Methods: We assessed the criterion validity of the SCQ for IBD patients by comparing patient-reported and clinician-reported comorbidities (as noted in the electronic health record) of the 13 diseases of the SCQ using Cohen’s kappa. Construct validity was assessed using the Spearman correlation coefficient between the SCQ and the Charlson Comorbidity Index (CCI), clinician-reported SCQ, quality of life, IBD-related healthcare and productivity costs, prevalence of disability, and IBD disease activity. We assessed responsiveness by correlating changes in the SCQ with changes in healthcare costs, productivity costs, quality of life, and disease activity after 15 months. Results: We included 613 patients. At least fair agreement (κ &gt; 0.20) was found for most comorbidities, but the agreement was slight (κ &lt; 0.20) for stomach disease [κ = 0.19, 95% CI (−0.03; 0.41)], blood disease [κ = 0.02, 95% CI (−0.06; 0.11)], and back pain [κ = 0.18, 95% CI (0.11; 0.25)]. Correlations were found between the SCQ and the clinician-reported SCQ [ρ = 0.60, 95% CI (0.55; 0.66)], CCI [ρ = 0.39, 95% CI (0.31; 0.45)], the prevalence of disability [ρ = 0.23, 95% CI (0.15; 0.32)], and quality of life [ρ = −0.30, 95% CI (−0.37; −0.22)], but not between the SCQ and healthcare or productivity costs or disease activity (|ρ| ⩽ 0.2). A change in the SCQ after 15 months was not correlated with a change in any of the outcomes.Conclusion: The SCQ is a valid tool for measuring comorbidity in IBD patients, but face and content validity should be improved before being used to correct case-mix differences.</p

Oligomeric Coiled-Coil Adhesin YadA Is a Double-Edged Sword

Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Suprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadAV98D,N99A. The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions

Wider Access to Genotypic Space Facilitates Loss of Cooperation in a Bacterial Mutator

Understanding the ecological, evolutionary and genetic factors that affect the expression of cooperative behaviours is a topic of wide biological significance. On a practical level, this field of research is useful because many pathogenic microbes rely on the cooperative production of public goods (such as nutrient scavenging molecules, toxins and biofilm matrix components) in order to exploit their hosts. Understanding the evolutionary dynamics of cooperation is particularly relevant when considering long-term, chronic infections where there is significant potential for intra-host evolution. The impact of responses to non-social selection pressures on social evolution is arguably an under-examined area. In this paper, we consider how the evolution of a non-social trait – hypermutability – affects the cooperative production of iron-scavenging siderophores by the opportunistic human pathogen Pseudomonas aeruginosa. We confirm an earlier prediction that hypermutability accelerates the breakdown of cooperation due to increased sampling of genotypic space, allowing mutator lineages to generate non-cooperative genotypes with the ability to persist at high frequency and dominate populations. This may represent a novel cost of hypermutability

Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening