Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 136, January 1975

This special bibliography lists 238 reports, articles, and other documents introduced into the NASA scientific and technical information system in December 1974

The effects of booster breaks during a sedentary night shift on physiological, psychomotor, psycho-physiological, and cognitive performance over a 3 night shift habituation phase

Despite extensive research into shift work, workers working under rotating shift conditions are still plagued by the effects of the desynchronisation resulting from working against their natural circadian rhythms. Additionally, modern industries are shifting towards tasks requiring greater cognitive demand with less manual labour incorporated into the tasks. Research into operator based tasks, and hence those of a sedentary cognitive base both during day and night shifts, has been focusing on the effectiveness of the standard rest/break schedule. Research indicating that the standard rest break schedule is often ineffective in eliminating operator discomfort and performance deterioration, with these affects argued to be more pronounced during a night shift schedule. Therefore current research set out to investigate alternative rest break schedules, incorporating a short bout of physical activity and stretching exercises which are proposed to enhance performance and subjective mood, while eliminating operator discomfort for sedentary based cognitive tasks. Three conditions were tested during a three day habituation shift cycle within a laboratory, incorporating two night shift groups (control and experimental) and a control day shift group. Twelve subjects made up each group, with the two night shift groups completing the shift schedule together. The control groups followed a typical 8 hour shift schedule while the experimental group performed a booster break (exercise and stretches) activity for 7.5 minutes every hour during the night shift schedule. Over the course of the shift, subjects completed a battery of six tests providing data on physiological measurements (heart rate and temperature), performance criteria (reaction time responses, memory and neurobiological) and subjective measures. Responses obtained for all the different parameters measured indicated a strong circadian influence for the majority of the variables, indicating the course of natural down regulation within physiological and performance criteria over the night shift. The booster break significantly improved reaction time performance, subjective ratings and resulted in a high sustainable activity level. Day shift comparisons indicating that within subjective measures and reaction time performance, the booster break resulted in similar responses to those of the day shift workers, while the control night shift groups reported significantly lowers results. Additionally, the booster break had positive influences during the circadian nadir, significantly improving parameters of performance and subjective ratings of sleepiness. The results of this study indicating which variables are strong predictors and indicators of the oscillations in performance and subjective ratings due to the circadian changes. The booster break interventions had positive effects on subjective ratings and reaction time performance, while also being argued to decrease the burden placed on the cardiac system as a result of increased sympathetic tone during the night shift, while additionally resulting in similar responses to those of day shift workers. Further studies are required, however, to provide conclusive evidence particularly within a working situation over a longer shift schedule

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 138

This special bibliography lists 343 reports, articles, and other documents introduced into the NASA scientific and technical information system in January 1975

A question based approach to drug development

As shown in the previous case study, changing the development plan from phase/time oriented to question based can improve the insights on the information that needs to be obtained and will help display the priorities within the program. In conventional phase-based drug development, timing is not the most important issue, as long as studies are performed rapidly. In this thesis, it is shown that the order in which studies are performed has a significant impact on the efficiency and quality of the drug development process. The impact of this novel approach can best be demonstrated by calculation of the financial consequences of resolving the right questions at the right time, during the development of new compounds. This calculation is based on the real-option theory, applied to drug development questions. Simple decision analyses suffice to determine the best sequence of research projects, and detailed pharmaco-economic models are unnecessary for this purpose. The thesis also provides some examples of research projects that were performed at different stages of drug development, with widely different consequences for the values of the projects concernedUBL - phd migration 201

Human pharmacology of current and novel gaba(a)-ergic treatments for anxiety

The GABAergic system has been implicated in the pathogenesis of various anxiety disorders. Pharmacological treatments, like benzodiazepines, have been proven to target the GABA(A) receptors and exert quick-onset anxiolytic effect in anxiety patients. However, the side effects of these non-selective GABA(A)ergic compounds, such as sedation, postural imbalance, or potential abuse, limit their use for clinical anxiolysis. Based on the understanding of benzodiazepines’ mechanism of action, the emergence of α2,3 subtype-selective GABA(A) modulator is expected to provide a novel pharmacological approach that alleviates anxiety symptoms but spares the common undesired side effects. Most of these compounds are still in early clinical development, in which stage proof-of-mechanism studies are usually performed in healthy volunteers. The findings from our studies consistently present a similar pattern in the pharmacodynamic effect profiles of the α2,3 subtype-selective GABA(A) modulators versus those of the non-selective full GABA(A) agonist, lorazepam. Future application of anxiogenic symptom provocation models that combine subjective measurements and/or neuroendocrine biomarker assays may provide further construct validity for clinical anxiolytic effects of α2,3 subtype-selective GABA(A) modulators. Also, such findings are expected to provide insights into the translation of preclinical pharmacological properties of α2,3-subtype-selective GABA(A)ergic compounds to clinical effects in anxiety patients through human pharmacology studies. LUMC / Geneeskunde Repositoriu

Detecting fatigue in car drivers and aircraft pilots by using eye-motion metrics

Fatigue is widely recognised for risking the safety of aviation and ground transportation. To enhance transport safety, fatigue detection systems based on psychophysiological measures have been under development for many years. However, a reliable and robust fatigue detection system is still missing. This thesis starts with a literature review of fatigue concepts in the transportation field and the current psychophysiological measures to fatigue, and narrows down the focus to improving fatigue detection systems using eye-motion measures. A research gap was identified between current fatigue systems only focusing on part of sleepy symptoms and a comprehensive fatigue detection system including mental fatigue needed. To address this gap, four studies were conducted to reshape the understanding of fatigue in transportation and explore effective eye-motion metrics for indicating fatigue considering different causal factors. Studies 1 and 2 investigated the influence of two types of task-related fatigue on eye movement. Twenty participants completed a vigilance task before and after a 1-h simulator-based drive with a secondary task. Forty participants, divided equally into two groups, finished the same task before and after a 1-h and 1.5-h monotonous driving task. The results demonstrated that two types of task-related fatigue caused by cognitive overload and prolonged underload induced different physiological responses to eye-motion metrics. The results also proved that the increased mental fatigue decreased driver’s vigilance. Studies 3 and 4 simulated two hazardous fatigue scenarios for pilots. Study 3 explored the relationship between eye-motion metrics and pilot fatigue in an underload flight condition with sleep deprivation (low workload and sleep pressure). Study 4 explored the effective eye-motion metrics to estimate pilot’s cognitive fatigue imposed by time on task and high workload. The results suggested different eye-motion metrics to indicate sleepiness and mental fatigue. In addition, based on the sleepiness and mental fatigue indicators in Studies 3 and 4, several classifiers were built and evaluated to accurately detect sleepiness and mental fatigue. These findings show that considering casual factors such as sleep pressure, time on task and workload when using eye-motion metrics to detect fatigue can improve the accuracy and face validity of the current fatigue detection systems

Development of new methodologies for the clinical, objective and automated evaluation of visual function based on the analysis of ocular movements : application in visual health

Premi Extraordinari de Doctorat, promoció 2018-2019. Àmbit de CiènciesHealthy visual function not only relies on good visual acuity. Other systems such as accommodation or binocular vision need to be effective. Binocular vision is the ability of the visual system to coordinate and integrate the information received separately from the two eyes into a single binocular percept. Anomalies in the binocular vision system lead to dysfunctions which are often associated with symptoms like asthenopia, diplopia, or ocular strain. The most prevalent non-strabismic binocular dysfunction is convergence insufficiency. The tests typically used to evaluate binocular vision and diagnose binocular dysfunctions essentially consist in eliciting eye movements and asking the patients to report when they perceive diplopia or single vision. In a conventional optometric clinical setting, they are generally run subjectively, as their results depend on the answers of the patients or on the examiner’s criteria. However, there exist instruments to determine the gaze position and measure ocular movements objectively, i.e. eye-trackers. These instruments are used as research tools in a wide range of applications (neuroscience, psychology, marketing, computer science, ophthalmology, etc.). Eye tracking systems are seldom used in optometric clinical practice, although it seems reasonable to think that the evaluation of binocular vision could better rely on eye tracking systems rather than subjective observations. In this context, the main objective of this thesis is to develop new methodologies for the clinical, objective and automated evaluation of visual function based on the analysis of ocular movements. This thesis is divided in 4 studies. In the first study, new methods for an eye tracking system based on multiple corneal reflections are proposed. The other 3 studies aim to analyze ocular movements in clinically interesting situations for the objective and automated evaluation of binocular vision. The results of the first study showed that the light sources configurations that produced the reflections in the lower region of the cornea showed higher accuracy. Vertical accuracy was slightly better with a higher number of corneal reflections. However, the proposed normalization methods improved vertical accuracy and counteracted the tendency for increasing accuracy with the number of glints. As a result, if the light sources are optimally positioned to avoid the interference of the eyelids and the normalization methods are applied, there is no need for more than two light sources. In the second study, an automated and objective method to measure phoria was proposed. It was significantly more repeatable than two other conventional clinical methods. However, the phoria results of the three tests were not interchangeable. This study brings to light several advantages of using eye-trackers in optometric clinical settings. The third study analyzes the characteristics of saccadic movements that occur during the near point of convergence test. The results showed that saccadic amplitude increased and rate decrease at closer viewing distances. These changes might be explained by the more rapid change of vergence demand and the greater angular size of the fixation target at near than at far. In general, saccades contributed to correct vergence errors and fixation position errors of the dominant eye. Finally, the fourth study focuses on the effects of the stimulus’ predictability on the latency and response time of vergence step movements. The results confirmed that vergence movements to predictable stimulus had shorter latency and response time than when the stimulus was random. Latency of convergence and divergence movements was influenced by the direction of the phoria. Other factors such as attention or voluntary effort might also affect vergence responses. All these effects might influence the final result of the vergence facility test, although further research is needed to specify the impact on the clinical test.Una bona funció visual no és sinònim exclusivament de bona agudesa visual. Cal que altres sistemes com l’acomodatiu o la visió binocular siguin eficaços. La visió binocular és la capacitat del sistema visual per coordinar i integrar la informació que reben els dos ulls en una única percepció. Anomalies en el sistema de visió binocular poden donar lloc a disfuncions associades a símptomes com astenopia, o visió doble. La disfunció no estràbica de la visió binocular més prevalent és la insuficiència de convergència. Els tests que normalment es fan per avaluar la visió binocular es basen en estimular moviments oculars i demanar als pacients que indiquin quan veuen doble i quan fusionen. A la pràctica clínica convencional, aquests tests solen ser subjectius. No obstant, hi ha instruments que serveixen per determinar objectivament la posició de mirada i mesurar els moviments oculars: els eye-trackers o instruments de seguiment de mirada. Aquests instruments s’utilitzen en recerca en moltes disciplines (neurociència, psicologia, marketing, oftalmologia, etc.). Tot i que una aplicació directa dels eye-trackers podria ser en l’avaluació de la visió binocular, els sistemes de seguiment de mirada gairebé no s’utilitzen en la pràctica clínica optomètrica. En aquest context, l’objectiu principal d’aquesta tesi és desenvolupar noves metodologies per a l’avaluació clínica, objectiva i automatitzada de la funció visual basades en l’anàlisi dels moviments oculars. La tesi està estructurada en 4 estudis. En el primer, es proposen nous mètodes per a un eye-tracker basat en múltiples reflexos corneals. Els altres 3 estudis tenen com a objectiu analitzar els moviments oculars en situacions d’interès clínic per avaluar objectiva i automàticament la visió binocular. Els resultats del primer estudi demostren que les configuracions d’il·luminació dels eye-trackers que formen les reflexions corneals a la zona inferior de la còrnia són més precises. La precisió vertical és lleugerament millor amb més fonts de llum. Tot i això, els mètodes de normalització proposats milloren considerablement la precisió vertical i contraresten la tendència de més precisió amb més fonts de llum. D’aquesta manera, si les fonts de llum no interfereixen amb les parpelles i s’apliquen els mètodes de normalització, no cal que els eye-trackers tinguin més de dues fonts de llum. En el segon estudi s’ha proposat un mètode automàtic i objectiu per mesurar la fòria. Aquest mètode és significativament més repetitiu que dos altres mètodes clínics. Tot i això, els resultats amb els tres mètodes no són intercanviables. Aquest estudi posa de manifest avantatges que podrien tenir els eye-trackers a la pràctica clínica optomètrica. En el tercer estudi s’analitzen les característiques dels moviments sacàdics que es produeixen durant la prova del punt proper de convergència. Els resultats demostren que l’amplitud dels sacàdics augmenta i la freqüència disminueix a mesura que s’escurça la distància. Aquests canvis poden ser deguts a que la demanda de vergència canvia més ràpid a distàncies properes que llunyanes, i a l’increment de la mida angular de l’objecte de fixació. En general, els sacàdics contribueixen a corregir els errors de vergència i els errors de fixació de l’ull dominant. Finalment, el quart estudi se centra en els efectes de la predictibilitat de l’estímul en la latència i temps de resposta dels salts de vergència. Els resultats confirmen que els moviments de vergència tenen una latència i temps de resposta més curts quan l’estímul es predictible que quan és aleatori. La latència dels moviments de convergència i divergència està influenciada per la direcció de la fòria. Altres factors com el grau d’atenció o d’esforç voluntari pot ser que afectin els moviments de vergència. Tots aquests efectes probablement influencien en el resultat final de la prova de la instal·lació de vergència, encara que es necessiten més investigacions per especificar l'impacte en la prova clínica.Award-winningPostprint (published version