Reverse Engineering Biological Control Systems for Applications in Process Control.

The main emphasis of this dissertation is the development of nonlinear control strategies based on biological control systems. Commonly utilized biological control schemes have been studied in order to reverse engineer the important concepts for applications in process control. This approach has led to the development of a nonlinear habituating control strategy and nonlinear model reference adaptive control schemes. Habituating control is a controller design strategy for nonlinear systems with more manipulated inputs than controlled outputs. Nonlinear control laws that provide input-output linearization while simultaneously minimizing the cost of affecting control are derived. Local stability analysis shows the controller can provide a simple solution to singularity and non-minimum phase problems. A direct adaptive control strategy for a class of single-input, single-output non-linear systems is presented. The major advantage is that a detailed dynamic non-linear model is not required for controller design. Unknown controller functions in the associated input-output linearizing control law are approximated using locally supported radial basis functions. Lyapunov stability analysis is used to derive parameter update laws which ensure the state vector remains bounded and the plant output asymptotically tracks the output of a linear reference model. A nonlinear model reference adaptive control strategy in which a linear model (or multiple linear models) is embedded within the nonlinear controller is presented. The nonlinear control law is constructed by embedding linear controller gains derived from models obtained using standard linear system identification techniques within the associated input-output linearizing control law. Higher-order controller functions are approximated with radial basis functions. Lyapunov stability analysis is used to derive stable parameter update laws. The major disadvantage of the previous techniques is computational expense. Two modifications have been developed. First, the effective dimension is reduced by applying nonlinear principal component analysis to the state variable data obtained from open-loop tests. This allows basis functions to be placed in a lower dimensional space than the original state space. Second, the total number of basis functions is fixed a priori and an algorithm which adds/prunes basis function centers to surround the current operating point on-line is utilized

Revision of Madagascar's Dwarf Lemurs (Cheirogaleidae:Cheirogaleus): Designation of Species, Candidate Species Status and Geographic Boundaries Based on Molecular and Morphological Data

The genus Cheirogaleus, the dwarf lemurs, is a radiation of strepsirrhine primates endemic to the island of Madagascar. The dwarf lemurs are taxonomically grouped in the family Cheirogaleidae (Infraorder: Lemuriformes) along with the genera Microcebus, Mirza, Allocebus, and Phaner. The taxonomic history of the genus Cheirogaleus has been controversial since its inception due to a paucity of evidence in support of some proposed species. In this study, we addressed this issue by expanding the geographic breadth of samples by 91 individuals and built upon existing mitochondrial (cytb and COII) and nuclear (FIBA and vWF) DNA datasets to better resolve the phylogeny of Cheirogaleus. The mitochondrial gene fragments D-loop and PAST as well as the CFTR-PAIRB nuclear loci were also sequenced. In agreement with previous genetic studies, numerous deep divergences were resolved in the C. major, C. minor and C. medius lineages. Four of these lineages were segregated as new species, seven were identified as confirmed candidate species, and four were designated as unconfirmed candidate species based on comparative mitochondrial DNA sequence data gleaned from the literature or this study. Additionally, C. thomasi was resurrected. Given the widespread distribution of the genus Cheirogaleus throughout Madagascar, the methodology employed in this study combined all available lines of evidence to standardize investigative procedures in a genus with limited access to type material and a lack of comprehensive sampling across its total distribution. Our results highlighted lineages that likely represent new species and identified localities that may harbor an as-yet undescribed cryptic species diversity pending further field and laboratory work.We are most grateful to the Ahmanson Foundation, the Theodore F. and Claire M. Hubbard Family Foundation, the Primate Action Fund / Conservation International, the Margot Marsh Biodiversity Foundation, and the National Geographic Society, for financial assistance

Wellbeing measures for workers: a systematic review and methodological quality appraisal

IntroductionIncreasing attention on workplace wellbeing and growth in workplace wellbeing interventions has highlighted the need to measure workers' wellbeing. This systematic review sought to identify the most valid and reliable published measure/s of wellbeing for workers developed between 2010 to 2020.MethodsElectronic databases Health and Psychosocial Instruments, APA PsycInfo, and Scopus were searched. Key search terms included variations of [wellbeing OR “well-being”] AND [employee*OR worker*OR staff OR personnel]. Studies and properties of wellbeing measures were then appraised using Consensus-based Standards for the selection of health Measurement Instruments.ResultsEighteen articles reported development of new wellbeing instruments and eleven undertook a psychometric validation of an existing wellbeing instrument in a specific country, language, or context. Generation and pilot testing of items for the 18 newly developed instruments were largely rated 'Inadequate'; only two were rated as 'Very Good'. None of the studies reported measurement properties of responsiveness, criterion validity, or content validity. The three instruments with the greatest number of positively rated measurement properties were the Personal Growth and Development Scale, The University of Tokyo Occupational Mental Health well-being 24 scale, and the Employee Well-being scale. However, none of these newly developed worker wellbeing instruments met the criteria for adequate instrument design.DiscussionThis review provides researchers and clinicians a synthesis of information to help inform appropriate instrument selection in measurement of workers' wellbeing.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=79044, identifier: PROSPERO, CRD42018079044

A retrospective observational research study to describe the real-world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands

ObjectivesTo describe the real-world effectiveness and safety of bosutinib in patients with chronic myeloid leukemia (CML).MethodsThis was a multi-center, retrospective, non-interventional chart review study conducted in 10 hospitals in the United Kingdom and the Netherlands.ResultsEighty-seven patients were included. Bosutinib was the third-line tyrosine kinase inhibitor (TKI) in 33 (38%) and fourth-line in 44 (51%) patients. Median treatment duration was 15.6 months. Among 84 patients in chronic phase (CP) at baseline, 26 (31%) switched to bosutinib due to resistance and 57 (68%) due to intolerance to prior TKIs. Cumulative complete cytogenetic and major molecular response rates in CP patients were 67% and 55%, respectively. After a median follow-up of 21.5 months, nine (11%) patients in CP died; estimated overall survival rates at 1 and 2 years postbosutinib initiation were 95% and 91%, respectively. Overall, 33/87 (38%) patients discontinued bosutinib due to either lack of efficacy/disease progression (17%), adverse events (14%), death (2%), or other reasons (5%). Eighty-two (94%) patients experienced ≥1 adverse event possibly related to bosutinib, most commonly diarrhea (52%).ConclusionsBosutinib used in routine clinical practice in heavily pretreated patients with CML is an effective treatment for patients in CP and is generally tolerable

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text