Unlike most of the specialities treated in this volume, control system design is still an art, not a science. These lectures are an attempt to produce a primer for prospective practitioners of this art. A large modern accelerator requires a comprehensive control system for commissioning, machine studies and day-to-day operation. Faced with the requirement to design a control system for such a machine, the control system architect has a bewildering array of technical devices and techniques at his disposal, and it is our aim in the following chapters to lead him through the characteristics of the problems he will have to face and the practical alternatives available for solving them. We emphasize good system architecture using commercially available hardware and software components, but in addition we discuss the actual control strategies which are to be implemented since it is at the point of deciding what facilities shall be available that the complexity of the control system and its cost are implicitly decided. 19 references.
<div>AbstractPurpose:<p>In the placebo-controlled SPARTAN study, apalutamide added to androgen-deprivation therapy (ADT) improved metastasis-free survival, second progression-free survival (PFS2), and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Mechanisms of resistance to apalutamide in nmCRPC require evaluation.</p>Patients and Methods:<p>In a subset of patients from SPARTAN, aberrations were assessed at baseline and end of study treatment (EOST) using targeted next-generation sequencing or qRT-PCR. Circulating-tumor DNA (ctDNA) levels were assessed qualitatively. Select aberrations in androgen receptor (AR) and other common PC-driving genes were detected and summarized by the treatment group; genomic aberrations were summarized in ctDNA-positive samples. Association between detection of aberrations in all patients and outcomes was assessed using Cox proportional-hazards models and multivariate analysis.</p>Results:<p>In 247 patients, the overall prevalence of ctDNA, AR aberrations, and <i>TP53</i> inactivation increased from baseline (40.6%, 13.6%, and 22.2%) to EOST (57.1%, 25.4%, and 35.0%) and was comparable between treatment groups at EOST. In patients who received subsequent androgen signaling inhibition after study treatment, detectable biomarkers at EOST were significantly associated with poor outcomes: ctDNA with PFS2 or OS (HR, 2.01 or 2.17, respectively; <i>P</i> < 0.0001 for both), any AR aberration with PFS2 (1.74; <i>P</i> = 0.024), and <i>TP53</i> or <i>BRCA2</i> inactivation with OS (2.06; <i>P</i> = 0.003; or 3.1; <i>P</i> < 0.0001).</p>Conclusions:<p>Apalutamide plus ADT did not increase detectable AR/non-AR aberrations over ADT alone. Detectable ctDNA, AR aberrations, and <i>TP53/BRCA2</i> inactivation at EOST were associated with poor outcomes in patients treated with first subsequent androgen signaling inhibitor.</p></div>
Mobility is associated with driving a vehicle. Age-related declines in the abilities of older persons present certain obstacles to safe driving. The negative effects of driving cessation on older adults' physical, mental, cognitive, and social functioning are well reported. Automated driving solutions represent a potential solution to promoting driver persistence and the management of fitness to drive issues in older adults. Technology innovation influences societal values and raises ethical questions. The advancement of new driving solutions raises overarching questions in relation to the values of society and how we design technology (a) to promote positive values around ageing, (b) to enhance ageing experience, (c) to protect human rights, (d) to ensure human benefit and (e) to prioritise human well-being. To this end, this chapter reviews the relevant ethical considerations in relation to assisted driving solutions. Further, it presents a new ethically aligned system concept for assisted driving. It is argued that human benefit, well-being and respect for human identity and rights are important goals for new automated driving technologies. Enabling driver persistence is an issue for all of society and not just older adult.
The role of transport in the health and wellbeing of older people is increasingly recognized: driving is the main form of personal transportation across the adult life-span. Patterns of changed mobility and driving cessation are an important focus of research. We investigated cross-sectional changes in driving as the main form of transportation and the frequency of such driving. The impact of Gender and Marital Status on Driver Status was also examined along with the reasons cited for ceasing driving. The impact that Driver Status had on Quality of Life and Loneliness was also assessed. Questionnaire based data from the Irish longitudinal study on aging (TILDA), a stratified clustered sample of 8163 individuals representative of the community dwelling population aged 50 years and over between 2009 and 2011 were examined. Driving oneself was identified by 76.1% as their most frequently used form of transport. Only for 80+ participants in Rural and Urban non-Dublin was it the second most popular option, being replaced by Being driven by someone else. Less women identified Driving oneself as their most frequently used option and they experienced an almost linear decline in uptake with Age. The uptake reported by men remained high up to 69 and only after this point did it begin to decline. A greater proportion of men were Current drivers with a similar pattern being shown by women in relation to Never drivers. Irrespective of Gender, married participants were more likely to drive. A greater proportion of women cited a reason other than health for giving up driving. Three reasons for giving up were impacted by Age category of which Physical incapacity was not one. Driving status impacted positively on Quality of Life and Loneliness. The results are discussed in light of the advantages to society of older drivers continuing to drive.
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