Control Experience Research Articles

A COMPREHENSIVE ANALYSIS OF COMPETENCY AND TRAINING PERSPECTIVES AMONG AIR TRAFFIC CONTROLLERS

The aim of the study was to examine air traffic controllers’ perspectives on competency, performance, and training. Analysing data from 182 participants, the results revealed a strong focus on competency with the controllers actively evaluating their skills. Notably, the experienced controllers (19+ years) displayed a heightened commitment to continuous learning, reflected in their higher participation in individual training and perception of its value for their career goals and adaptation to the evolving aviation industry. Competency-based training programs also received positive feedback across experience levels, highlighting their potential effectiveness. Moreover, training was universally perceived as key to performance throughout careers. These results highlighted the importance of fostering a culture of continuous learning within air traffic control (ATC) communities. Aviation authorities can support this by providing diverse training opportunities, including individual and competency-based programs. Future research should continue investigating the impact of technological advancements and AI/machine learning on ATC competencies, the effectiveness of competency-based training programs, and the role of individual training in competency development, ultimately ensuring the vital role of air traffic controllers in aviation safety.

Influence of decision-making algorithms on the diagnostic accuracy using the current classification of periodontal diseases—a randomized controlled trial

ObjectivesTo examine the influence of the decision-making algorithms published by Tonetti and Sanz in 2019 on the diagnostic accuracy in two differently experienced groups of dental students using the current classification of periodontal diseases.Materials and methodsEighty-three students of two different clinical experience levels were randomly allocated to control and study group, receiving the staging and grading matrix, resulting in four subgroups. All diagnosed two patient cases with corresponding periodontal charts, panoramic radiographs, and intraoral photographs. Both presented severe periodontal disease (stage III, grade C) but considerably differed in complexity and phenotype according to the current classification of periodontal diseases. Controls received the staging and grading matrix published within the classification, while study groups were additionally provided with decision-trees published by Tonetti and Sanz. Obtained data was analyzed using chi-square test, Spearman’s rank correlation, and logistic regression.ResultsUsing the algorithms significantly enhanced the diagnostic accuracy in staging (p = 0.001*, OR = 4.425) and grading (p < 0.001**, OR = 30.303) regardless of the clinical experience. In addition, even compared to the more experienced control, less experienced students using algorithms showed significantly higher accuracy in grading (p = 0.020*). No influence on the criteria extent could be observed comparing study groups to controls.ConclusionThe decision-making algorithms may enhance diagnostic accuracy in dental students using the current classification of periodontal diseases.Clinical relevanceThe investigated decision-making algorithms significantly increased the diagnostic accuracy of differently experienced under graduated dental students and might be beneficial in periodontal education.

Brain structure adapts dynamically to highly demanding bilingual experiences: Insights from interpreters and translators

It remains an open question how the brain adapts structurally to handle strenuous cognitive challenges. Interpreters and translators rely on high cognitive control to regulate two languages in their jobs, which makes them ideal models in investigating experience-based neuroplasticity induced by exceptional cognitive demands. Using structural MRI, we compare volumes of the caudate nucleus and putamen, structures involved in bilingual language control, in three groups of highly experienced bilinguals: translators, interpreters and highly experienced bilinguals. Between-group comparisons revealed larger volumes for both structures in interpreters and translators compared to highly experienced bilinguals. We used Bayesian Generalized Additive Mixed Models to model effects of quantified general bilingual experiences on the structures of interest. Critically, dynamic, group-specific volumetric trajectories of the ROIs related to general bilingual experiences were revealed. Specifically, whereas caudate volumes increased as a function of bilingual experiences across all groups, they started to return to baseline volumes at the high points of experiences in the two professional groups only. As for the putamen, the expansion-renormalisation pattern was replicated in interpreters only, whereas in translators and highly experienced controls, putamen volumes simply increased as a function of bilingual experiences. This pattern of results suggests that bilingualism-related brain adaptations manifest differently in different brain regions and are modulated by quantitative and qualitative differences in bilingual experiences. These findings shed new light on the ways in which extremely demanding bilingual experiences affect neuroplasticity in bilinguals.

Gamma Knife Radiosurgery for Cushing’s Disease: Evaluation of Biological Effective Dose from a Single-Center Experience

Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing's disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS.

Neural correlates of control over pain in fibromyalgia patients

The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings.

Settling Time Optimization in Wire Bonder Systems via Extremum-Seeking Control1

Adequate tuning of control laws is essential for high positioning accuracy, large system throughput, and reliability in high-end mechatronic and robotic systems. However, a population of such systems generally shows slight variations in dynamic responses due to, e.g., manufacturing tolerances, different disturbance situations, or position-dependent dynamics. Given the time-consuming nature of controller design, even by experienced control engineers, typically just one control law is designed for the whole system population based on worst-case bounds on variations in dynamic responses, resulting in a loss of individual system performance. The main contribution of this paper is the development of an automated controller tuning approach, based on extremum-seeking control, for settling time optimization via individual controller tuning. While other automated controller tuning methods exist, the developed approach allows inclusion of closed-loop stability and robustness constraints based solely on non-parametric frequency-response measurements of open-loop plant dynamics, and therewith directly optimizes transient system performance in a purely data-based manner. The proposed approach has been applied in simulation in an industrial case study for settling time optimization in point-to-point motions of a wire bonder system. In this case study, the effectiveness of the approach has been shown by achieving significant performance increases of 39.4% and 40.6% compared to controllers designed by experienced control engineers using manual loop-shaping techniques and a frequency-based auto-tuner, respectively, without needing manual tuning effort.

Immunotherapy treatment responses in hepatocellular carcinoma patients with nonalcoholic fatty liver disease cirrhosis.

e16199 Background: Primary liver cancer is the third most frequent cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) composing 75% of cases. Recent preclinical models suggest that immunotherapy targeting programmed cell death protein 1 (PD-1) leads to CD8+ T-cell activation but not tumor regression in nonalcoholic fatty liver disease (NAFLD) induced HCC. However, additional studies are required to understand the response of NAFLD-associated HCC patients to PD-1 and programmed death-ligand 1 (PD-L1) therapies. Methods: Our team conducted a retrospective, single center study to determine the best responses to anti-PD-1/PD-L1 containing regimens in patients with HCC and underlying NAFLD cirrhosis. There were 2 groups included in this study: patients with HCC associated with NAFLD cirrhosis and those who had HCC without NAFLD cirrhosis. All patients included in this study received either an anti-PD-1/PD-L1 targeted agent as monotherapy or combined with other systemic treatment. Radiologic evaluations were conducted between February 2018 and January 2022. Results: There were 81 patients were included in this study: 15 in the NAFLD cirrhosis HCC group and 66 in the HCC group without NAFLD cirrhosis. When determining the best responses to anti-PD-1/PD-L1 therapies, 6 patients (40%) with HCC and NAFLD cirrhosis had disease progression as their best responses versus 7 patients (10.6%) who had HCC without NAFLD cirrhosis (risk ratio 3.8, p = 0.012). Furthermore, in the HCC group without NAFLD cirrhosis, 59 patients (89.4%) experienced disease control (defined as stable disease, partial response, or complete response) from anti-PD-1/PD-L1 containing regimens compared to 9 patients (60%) in the NAFLD cirrhosis-related HCC group (risk ratio 1.5, p = 0.012). No significant differences were found in gender, patient age, or treatment regimens received between the two groups. See the table below for details on immunotherapy regimens and treatment responses. Conclusions: In this study, HCC patients with NAFLD cirrhosis experienced significantly higher rates of disease progression as the best response to anti-PD-1/PD-L1 therapies compared to HCC patients without NAFLD cirrhosis. As the use of immunotherapy in the HCC population continues to expand, additional prospective studies are necessary to clarify the impact of underlying liver disease on treatment response.[Table: see text]

Meditation-induced effects on whole-brain structural and effective connectivity

In the past decades, there has been a growing scientific interest in characterizing neural correlates of meditation training. Nonetheless, the mechanisms underlying meditation remain elusive. In the present work, we investigated meditation-related changes in functional dynamics and structural connectivity (SC). For this purpose, we scanned experienced meditators and control (naive) subjects using magnetic resonance imaging (MRI) to acquire structural and functional data during two conditions, resting-state and meditation (focused attention on breathing). In this way, we aimed to characterize and distinguish both short-term and long-term modifications in the brain’s structure and function. First, to analyze the fMRI data, we calculated whole-brain effective connectivity (EC) estimates, relying on a dynamical network model to replicate BOLD signals’ spatio-temporal structure, akin to functional connectivity (FC) with lagged correlations. We compared the estimated EC, FC, and SC links as features to train classifiers to predict behavioral conditions and group identity. Then, we performed a network-based analysis of anatomical connectivity. We demonstrated through a machine-learning approach that EC features were more informative than FC and SC solely. We showed that the most informative EC links that discriminated between meditators and controls involved several large-scale networks mainly within the left hemisphere. Moreover, we found that differences in the functional domain were reflected to a smaller extent in changes at the anatomical level as well. The network-based analysis of anatomical pathways revealed strengthened connectivity for meditators compared to controls between four areas in the left hemisphere belonging to the somatomotor, dorsal attention, subcortical and visual networks. Overall, the results of our whole-brain model-based approach revealed a mechanism underlying meditation by providing causal relationships at the structure-function level.

Action prediction modulates self–other integration in joint action

People often coordinate actions with others, requiring an adjustable amount of self–other integration between actor’s and co-actor’s actions. Previous research suggests that such self–other integration (indexed by the joint Simon effect) is enhanced by agent similarity of the co-actor (e.g., high in intentionality). In this study, we aimed to extend this line of research by testing whether experiencing agency over a co-actor’s actions (vicarious agency) and/or action prediction strengthens the joint Simon effect. For this purpose, we manipulated experienced agency by varying the experienced control over a co-actor’s actions (Experiment 1), and action prediction regarding the co-actor’s actions (Experiment 2). Vicarious agency could effectively be induced, but did not modulate the size of the joint Simon effect. The joint Simon effect was decreased when the co-actor’s actions were unpredictable (vs. predictable) during joint task performance. These findings suggest social agency can be induced and effectively measured in joint action. Action prediction can act as an effective agency cue modulating the amount of self–other integration in joint action.

Sense of Agency and User Experience: Is There a Link?

Sense of control is increasingly used as a measure of quality in human-computer interaction. Control has been investigated mainly at a high level, using subjective questionnaire data, but also at a low level, using objective data on participants’ sense of agency. However, it remains unclear how differences in higher level, experienced control reflect lower level sense of control. We study that link in two experiments. In the first one we measure the low-level sense of agency with button, touchpad, and on-skin input. The results show a higher sense of agency with on-skin input. In the second experiment, participants played a simple game controlled with the same three inputs. We find that on-skin input results in both increased sense and experience of control compared to touchpad input. However, the corresponding difference is not found between on-skin and button input, whereas the button performed better in the experiment task. These results suggest that other factors of user experience spill over to the experienced control at rates that overcome differences in the sense of control. We discuss the implications for using subjective measures about the sense of control in evaluating qualities of interaction.

Gender Norms, Control Over Girls’ Sexuality, and Child Marriage: A Honduran Case Study

PurposeThis study explores links among marianismo, girls’ mobility and sexuality, and child marriage among adolescent girls in rural areas of Honduras. MethodsWe analyze quantitative and qualitative data collected in 2008–2016 for a longitudinal cohort study of rural Honduran adolescent girls. These data include interviews (n = 10 married before age 18) and surveys (n = 563; 155 married early). We also use qualitative data from focus groups in 2016 that included students, parents, teachers, and community members (n = 120). ResultsWe find that girls who scored higher on a scale of traditional gender norms were more likely to marry early. Furthermore, our qualitative findings indicate that girls experienced control over their mobility and their sexuality because of rigid gender norms prevalent in their communities. The control girls experience clashes with undergoing psychosocial changes that are associated with increased desire for autonomy and intimacy as well as increased awareness of their sexuality. In some cases, girls believed that marriage was better than staying in their restrictive households, and/or they viewed marriage as the only way to have a romantic relationship. DiscussionRigid gender norms that promote excessive regulation of girls’ behavior and sexuality influence girls’ decision-making processes to enter child marriage. Educational initiatives that challenge sexist gender norms and explain and normalize attraction and intimacy during adolescence should be a central component of child marriage prevention programming for adolescents, parents, and community members.

A Gender Perspective on GDPR and Information Privacy

With the introduction of The General Data Protection Regulation (GDPR) in 2018, European citizens were granted stronger privacy protection. Despite privacy and GDPR being frequent topics of discussion, many consumers lack knowledge on how personal data are harvested for business purposes, and they are unaware of their rights. Drawing on a larger survey conducted in a Norwegian university college, this study investigates gender differences in privacy behaviour (n=444). We offer three insights. The results revealed that (1) respondents’ concern for privacy does not differ across gender, but men claimed to experience slightly more control over their personal data compared to women. (2) Exercising privacy rights were comparable across gender as women and men reported the same inclination to act on rights granted by GDPR. (3) Willingness to share information in return for benefits depended on the information in question. Men and women agreed in their willingness to exchange name and e-mail. However, women were less willing than men to give up more sensitive information, yet more willing to give up date of birthday, TV viewing history and shopping history. Our insights bring attention to a possible link between experienced control over own data and willingness to exchange data for benefits, highlighting a potential mediating relationship that could be worthwhile pursuing.

Paradoxical Role of Work for Indian Middle-Class Working Women Who Experience Partner Abuse

Work is a source of financial and psychological empowerment for middle-class women in intimate partner violence (IPV), but work can also exacerbate their vulnerabilities. Drawing on ethics of vulnerability, this study addressed the paradoxical yet integral role of work in the lives of Indian middle-class women who experience IPV. Using a hermeneutic phenomenological methodology, the study showed that Indian middle-class women in IPV experienced safety and support at work, but also experienced sexual harassment and discrimination. Work fostered autonomy and agency, but women experienced control and pressure. As work allowed them to experience transformation, it also disenfranchised them in their vulnerability. These findings not only highlight the complex nature of work for Indian middle-class women in IPV but also raise pertinent questions on who takes care of those in need. Drawing upon the model of organizational caregiving, this study makes a compelling argument for organizations to assume the moral obligation to genuinely engage in caring for their employees in IPV.

Moral Decision Making in Human-Agent Teams: Human Control and the Role of Explanations.

With the progress of Artificial Intelligence, intelligent agents are increasingly being deployed in tasks for which ethical guidelines and moral values apply. As artificial agents do not have a legal position, humans should be held accountable if actions do not comply, implying humans need to exercise control. This is often labeled as Meaningful Human Control (MHC). In this paper, achieving MHC is addressed as a design problem, defining the collaboration between humans and agents. We propose three possible team designs (Team Design Patterns), varying in the level of autonomy on the agent’s part. The team designs include explanations given by the agent to clarify its reasoning and decision-making. The designs were implemented in a simulation of a medical triage task, to be executed by a domain expert and an artificial agent. The triage task simulates making decisions under time pressure, with too few resources available to comply with all medical guidelines all the time, hence involving moral choices. Domain experts (i.e., health care professionals) participated in the present study. One goal was to assess the ecological relevance of the simulation. Secondly, to explore the control that the human has over the agent to warrant moral compliant behavior in each proposed team design. Thirdly, to evaluate the role of agent explanations on the human’s understanding in the agent’s reasoning. Results showed that the experts overall found the task a believable simulation of what might occur in reality. Domain experts experienced control over the team’s moral compliance when consequences were quickly noticeable. When instead the consequences emerged much later, the experts experienced less control and felt less responsible. Possibly due to the experienced time pressure implemented in the task or over trust in the agent, the experts did not use explanations much during the task; when asked afterwards they however considered these to be useful. It is concluded that a team design should emphasize and support the human to develop a sense of responsibility for the agent’s behavior and for the team’s decisions. The design should include explanations that fit with the assigned team roles as well as the human cognitive state.

Developing a Plan for the Sustainable Implementation of an Electronic Health Intervention (Partner in Balance) to Support Caregivers of People With Dementia: Case Study

BackgroundGiven the increasing use of digital interventions in health care, understanding how best to implement them is crucial. However, evidence on how to implement new academically developed interventions in complex health care environments is lacking. This case study offers an example of how to develop a theory-based implementation plan for Partner in Balance, an electronic health (eHealth) intervention to support the caregivers of people with dementia.ObjectiveThe specific objectives of this study were to (1) formulate evidence-based implementation strategies, (2) develop a sustainable business model, and (3) integrate these elements into an implementation plan.MethodsThis case study concerns Partner in Balance, a blended care intervention to support the caregivers of people with dementia, which is effective in improving caregiver self-efficacy, quality of life, and experienced control. The large-scale implementation of Partner in Balance took place in local dementia case-management services, local care homes, dementia support groups, and municipalities. Experiences from real-life pilots (n=22) and qualitative interviews with national stakeholders (n=14) were used to establish an implementation plan consisting of implementation strategies and a business model.ResultsThe main finding was the need for a business model to facilitate decision-making from potential client organizations, who need reliable pricing information before they can commit to training coaches and implementing the intervention. Additionally, knowledge of the organizational context and a wider health care system are essential to ensure that the intervention meets the needs of its target users. Based on these findings, the research team formulated implementation strategies targeted at the engagement of organizations and staff, dissemination of the intervention, and facilitation of long-term project management in the future.ConclusionsThis study offers a theory-based example of implementing an evidence-based eHealth intervention in dementia health care. The findings help fill the knowledge gap on the eHealth implementation context for evidence-based eHealth interventions after the trial phase, and they can be used to inform individuals working to develop and sustainably implement eHealth.

Usage of Chinese Herbs in Cancer Patients in Southern China: A Survey.

To study the use of Chinese medicine (CM) in cancer patients in southern China. A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

Brain STAT5 Modulates Long-Term Metabolic and Epigenetic Changes Induced by Pregnancy and Lactation in Female Mice.

Several metabolic and behavioral adaptations that emerge during pregnancy remain present after weaning. Thus, reproductive experience causes long-lasting metabolic programming, particularly in the brain. However, the isolate effects of pregnancy or lactation and the molecular mechanisms involved in these long-term modifications are currently unknown. In the current study, we investigated the role of brain signal transducer and activator of transcription-5 (STAT5), a key transcription factor recruited by hormones highly secreted during gestation or lactation, for the long-term adaptations induced by reproductive experience. In control mice, pregnancy followed by lactation led to increased body adiposity and reduced ambulatory activity later in life. Additionally, pregnancy+lactation induced long-term epigenetic modifications in the brain: we observed upregulation in hypothalamic expression of histone deacetylases and reduced numbers of neurons with histone H3 acetylation in the paraventricular, arcuate, and ventromedial nuclei. Remarkably, brain-specific STAT5 ablation prevented all metabolic and epigenetic changes observed in reproductively experienced control female mice. Nonetheless, brain-specific STAT5 knockout (KO) mice that had the experience of pregnancy but did not lactate showed increased body weight and reduced energy expenditure later in life, whereas pregnancy KO and pregnancy+lactation KO mice exhibited improved insulin sensitivity compared with virgin KO mice. In summary, lactation is necessary for the long-lasting metabolic effects observed in reproductively experienced female mice. In addition, epigenetic mechanisms involving histone acetylation in neuronal populations related to energy balance regulation are possibly associated with these long-term consequences. Finally, our findings highlighted the key role played by brain STAT5 signaling for the chronic metabolic and epigenetic changes induced by pregnancy and lactation.

Pattern-based NN control for uncertain pure-feedback nonlinear systems

Implementing human-like learning and control for nonlinear dynamical systems operating in different control situations is an important and challenging issue. This paper presents a pattern-based neural network (NN) control strategy for nonlinear pure-feedback systems via deterministic learning (DL). Firstly, an appropriately designed adaptive neural dynamic surface controller is proposed to achieve the finite time tracking control. By analyzing the recurrent property of NN input signals, a partial persistent excitation (PE) condition for radial basis function (RBF) network is established, the implicit desired control dynamics under different control situations are accurately identified via DL in the case that the dimension of NN input is reduced. And a set of pattern-based experienced actual and virtual controllers is constructed using the learned knowledge. Secondly, to classify different control situations, when the system is operating in different control situations but controlled by current normal experienced controller, the dynamics of each subsystem are accurately identified via DL, n sets of dynamical estimators are constructed using the learned knowledge. Thirdly, in the recognition phase, n sets of residuals are achieved by comparing each set of estimators with the monitored system, sudden change in the control situation is rapidly recognized based on the principle of the earliest occurrence of the minimum residual. Finally, in the control phase, according to the recognition result, the correct experienced actual and virtual controllers will be selected to control the plant, guaranteed stability and superior control performance are achieved without any further re-adaptation online. Simulation studies are given to verify the proposed scheme can not only acquire and memorize knowledge like humans, but also reuse the learned knowledge to achieve rapid recognition and control of current control situation.

FOLFIRINOX in pancreatic cancer patients age 75 years or older.

362 Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS) (11.1 vs 6.8 months [m] with gemcitabine, P &lt; 0.001), pts &gt; 75 yrs old were excluded from this study. As per SEER 2011-2015 data, 38% of new PC cases are diagnosed in pts age &gt; 75. The purpose of this study was to assess the safety and efficacy of FOLFIRINOX in this group of pts. Methods: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with FOLFIRINOX at MD Anderson since 2011. Data obtained include demographics, line of treatment (tx), starting dose, progression free survival (PFS), OS and toxicities. Response was determined by chart documentation. Primary outcomes were mOS and rates of grade 3/4 hematologic toxicity (HT). Results: A total of 24 pts (19 male) were included with median age of 76 (range 75 to 84). 18 had metastatic disease, and FOLFIRINOX was the 1st line of tx for 18 of the 24 pts. The median number of cycles administered was 4 (range 1 to 12). The most frequent starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m2, respectively. Bolus 5-FU and leucovorin were omitted in all but 3 pts. Median PFS was 3.7 m (95% CI: 3.0-5.7) with mOS of 11.6 m (95% CI: 6.14-15.7). 16 pts (67%) experienced disease control (response to tx or stable disease). Grade 3 or 4 HT occurred in 11 pts (46%), and 9 (38%) were supported with granulocyte colony-stimulating factor at some point during tx. 6 pts (25%) required hospital admission for any toxicity, most commonly infection (3 pts), and 10 (42%) stopped FOLFIRINOX due to toxicity, most commonly fatigue (6 pts). Conclusions: In this single-center retrospective analysis of 24 unresectable PC pts age 75 or older given FOLFIRINOX, OS outcomes were similar to those reported by Conroy et al in the original trial which excluded pts older than 75. In our review, toxicities including incidences of grade 3 or 4 HT were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar efficacy and toxicity when compared to younger pts.

Abstract 3627: Organ-specific differential responses to immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma

Abstract Background: Immune checkpoints inhibitors (ICIs) such as anti-PD-1/PD-L1 monoclonal antibodies exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). Immune microenvironments of different organs are often different and may affect the efficacy of immunotherapy. The study explores whether tumor response to ICIs of HCC may vary among different organs. Patients and Methods: We reviewed patients with advanced HCC who had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy, alone or in combination, in 3 medical centers in Taiwan. Patients with measurable diseases were enrolled. An organ-specific response criteria, modified from RECIST 1.1, allowing a maximum of 5 measurable lesions per organ system, was used to evaluate the responses to ICIs for tumors of individual organ system. The organ-specific complete responses (CR), partial responses (PR), stable diseases (SD), or progressive diseases (PD) were determined for individual organ system. Results: A total of 76 patients (Male: Female= 62: 14, median age of 59.1 years) with advanced HCC were enrolled. Among them, 51 (67.1%) and 12 (15.8%) patients had chronic hepatitis B virus or chronic hepatitis C infection. The ICI treatments included anti-PD-1 or anti-PD-L1 alone, anti-CTLA4 alone, and anti-PD-1/PD-L1 plus anti-CTLA4 combination in 59, 1, and 16 patients; 20 and 56 patients had received ICIs as first-line or ≥ 2nd-line therapy. The overall response rate (RR) by RECIST 1.1 was 28.9%. Fifty-nine, 34, 18, and 18 patients who had measurable hepatic tumors, lung, lymph node, and intra-abdomen metastases were subject to organ-specific response evaluation. Organ-specific RRs of hepatic tumors, lung, lymph node, and intra-abdomen metastases, were 23.7, 41.2, 27.8, and 38.9%, respectively. Among 39 patients who had both hepatic and extrahepatic tumors, 16 had significant differential responses between hepatic and extrahepatic tumors: 12 of them had disease control (CR/PR/SD) in extrahepatic tumors and PD in hepatic tumors, and 4 exhibited disease control in hepatic tumors and PD in extrahepatic tumors (p=0.046). Moreover, in 16 patients with only evaluable hepatic tumors and lung metastases, 8 had disease control in lung metastases and PD in hepatic tumors, and none experienced disease control in liver tumors and PD in lung metastases (p=0.005). Conclusions: The hepatic tumors of HCC are less responsive to ICIs than the extrahepatic lesions. Lung metastases show best response to ICIs. The underlying mechanism warrants further investigation. (This work is supported by grants from the Ministry of Science and Technology, Taiwan, MOST 106-2314-B-002-210). Citation Format: Li-Chun Lu, Chiun Hsu, Yu-Yun Shao, Yee Chao, Chia-Jui Yen, I-Lun Shih, Yi-Ping Hung, Chun-Jung Chang, Ying-Chun Shen, Jhe-Cyuan Guo, Tsung-hao Liu, Chih-Hung Hsu, Ann-Lii Cheng. Organ-specific differential responses to immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3627.