Thomas Roth - Academia.edu (original) (raw)

Papers by Thomas Roth

Journal of Clinical Sleep Medicine, 2007

port; and has participated in speaking engagements supported by Sanofi and Takeda. Dr. Scharf is ... more port; and has participated in speaking engagements supported by Sanofi and Takeda. Dr. Scharf is a member of Neurocrine Biosciences Insomnia Advisory Board. Dr. Lankford has served on the advisory board the speaker's bureau for Neurocrine Biosciences, Inc. Dr. Farber is employed by Neurocrine Biosciences. Inc. Dr. Rosenberg has indicated no other financial conflicts of interest.

Sleep, 1986

Performance measures were compared to the multiple sleep latency test (MSL T) as indices to asses... more Performance measures were compared to the multiple sleep latency test (MSL T) as indices to assess tolerance to the residual effects of benzodiazepine hypnotics during repeated nightly administration. Twelve healthy, normal sleepers received flurazepam 30 mg, temazepam 30 mg, and placebo for nine nights in a repeated measures, Latin-square design with 19 nights of recovery separating the treatments. As compared to placebo, both drugs altered sleep stage parameters in the early (nights 1-2) and late (nights 8-9) phases of the study. Hypnotic effects were found for both drugs in the early phase, but diminished for both in the late phase. The subjects' performance the next day was disrupted following treatment with flurazepam, but not with temazepam, during the early phase. Mean sleep latency on the MSLT was reduced by both drugs during the early phase. During the late phase, flurazepam did not disrupt performance but still affected the MSL T. Temazepam affected neither index the next day during the late phase.

Sleep Medicine, 2015

reported outcomes, total sleep time Role of the funding source: This study was funded by Organon,... more reported outcomes, total sleep time Role of the funding source: This study was funded by Organon, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ. Key individuals under the employment of Merck & Co., Inc. who were involved in the design and conduct of the study appear as authors on the manuscript, and were involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. HIGHLIGHTS  Esmirtazapine has a novel mechanism vs. other hypnotics (5-HT2A/H1 antagonist)  This 2-week outpatient study evaluated esmirtazapine vs. placebo in primary insomnia  Esmirtazapine significantly improved sleep onset, duration and quality vs. placebo  There was no evidence of rebound insomnia after discontinuation of esmirtazapine  Esmirtazapine was well tolerated; ≤7% of patients withdrew due to adverse events ABSTRACT Background: Esmirtazapine (Org 50081), a high-affinity antagonist at 5-HT 2A and H 1 receptors, was assessed for its hypnotic efficacy. Methods: In this double-blind, randomized study, non-elderly patients with primary insomnia (but otherwise healthy) were treated with esmirtazapine (1.5, 3.0, or 4.5 mg) or placebo for 2 weeks. The primary endpoint was patient-reported total sleep time (TST); other patient-reported endpoints included sleep latency (SL), wake time after sleep onset (WASO), number of awakenings, sleep quality, and satisfaction with sleep duration. Measures to assess the potential adverse effects of treatment included morning alertness, daytime function/napping, and rebound insomnia during a single-blind placebo run-out week after treatment ended. Adverse events (AEs) were also assessed. Results: Overall, 526 patients were randomized and 463 (88%) completed treatment. All esmirtazapine doses significantly improved TST, SL, sleep quality, and satisfaction with sleep duration versus placebo. Relative to placebo, TST was increased by 30-40 min and SL decreased by ~12 min for all doses. The highest dose (4.5 mg) also significantly reduced

Archiv der Pharmazie, 2014

A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones were prepared in se... more A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones were prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Whereas hydrazones derived from 3-benzoylpyridazines (IC 50 ¼ 0.99-8.74 mM) inhibited the proliferation of the tumor cell lines tested, the non-fully aromatic 3benzoylpyridazinone hydrazones (IC 50 > 10 mM) turned out to be inactive. Compounds E-1b (IC 50 ¼ 0.12 mM) and E-1d (IC 50 ¼ 0.18 mM) exert high cytotoxic activities in clonogenic assays involving human tumor cells of different tissue origins. In vivo application of compound E-1b (300 mg/kg/day) resulted in a 66% reduction in tumor burden.

Journal of Sleep Research, 2014

Review of Scientific Instruments, 2014

We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction ... more We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction in magnetic fields up to 31 T and at low temperature down to 1.5 K. The apparatus consists of a split-pair magnet, a liquid nitrogen bath to cool the pulsed coil, and a helium cryostat allowing sample temperatures from 1.5 up to 250 K. Using a 1.15 MJ mobile generator, magnetic field pulses of 60 ms length were generated in the magnet, with a rise time of 16.5 ms and a repetition rate of 2 pulses/hour at 31 T. The setup was validated for single crystal diffraction on the ESRF beamline ID06.

Sleep, 2014

To assess moderators, such as stressor chronicity, and mediators, including stress response in th... more To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Design: Longitudinal. Setting: Epidemiological. Participants: A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. Interventions: None. Measurements and Results: Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Conclusions: Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice.

Sleep, 2015

(AI), and sleepy insomniacs (SI). Measurements: Sleep parameters were assessed by sleep diary. Ci... more (AI), and sleepy insomniacs (SI). Measurements: Sleep parameters were assessed by sleep diary. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was measured using the multiple sleep latency test (MSLT). Brain activity was measured using the N1 event-related potential (ERP). A tandem repeat in PER3 was genotyped from saliva DNA. Results: (1) AI group showed normal MSLT scores but elevated N1 amplitudes indicating cortical hyperarousal. (2) SI group showed pathologically low MSLT scores but normal N1 amplitudes. (3) AI and SI groups were not significantly different from one another in circadian phase, while controls were significantly phase-delayed relative to both SWD groups. (4) AI showed significantly longer sleep latencies and lower sleep efficiency than controls during both nocturnal and diurnal sleep. SI significantly differed from controls in nocturnal sleep parameters, but differences during diurnal sleep periods were smaller and not statistically significant. (5) Genotype × phenotype χ 2 analysis showed significant differences in the PER3 VNTR: 9 of 10 shift workers reporting sleepiness in a post hoc genetic substudy were found to carry the long tandem repeat on PER3, while 4 of 14 shift workers without excessive sleepiness carried the long allele. Conclusions: Our results suggest that the sleepy insomnia phenotype is comprehensively explained by circadian misalignment, while the alert insomnia phenotype resembles an insomnia disorder precipitated by shift work.

Principles and Practice of Sleep Medicine, 2005

Physiology & Behavior, 2000

Study objectives: There is accumulating evidence that the common cold produces impairments in psy... more Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300 ± 0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3 ± 5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.

2013 IEEE 39th Photovoltaic Specialists Conference (PVSC), 2013

ABSTRACT Excess-carrier recombination lifetime is a key parameter in silicon solar cell design an... more ABSTRACT Excess-carrier recombination lifetime is a key parameter in silicon solar cell design and production. With the vast international use and recent standardization (SEMI PV13) of eddy-current wafer and brick silicon lifetime test instruments, it is important to quantify the inter- and intralaboratory repeatability. This paper presents the results of an international interlaboratory study conducted with 24 participants to determine the precision of the SEMI PV13 eddy-current carrier lifetime measurement test method. Overall, the carrier recombination lifetime between-laboratory reproducibility was found to be within ±11% for the quasi-steady-state mode and ±8% for transient mode for wafer samples, and within ±4% for bulk samples.

Traffic Injury Prevention, 2014

Sleep Medicine Clinics, 2010

Polysomnographic (PSG) studies, which refers to the simultaneous recording of multiple electrophy... more Polysomnographic (PSG) studies, which refers to the simultaneous recording of multiple electrophysiological parameters [i.e., electrooculogram (EOG), electromyogram (EMG), and electroencephalogram (EEG)] during sleep, have demonstrated that sleep is a complex, highly organized biological state composed of two distinct brain states, rapid eye movement (REM) and non rapid eye movement (NREM) sleep (1,2). In terms of EEG activity, NREM sleep is characterized by EEG slowing and increased voltage relative to the low voltage (10-30 microvolts) and fast frequency (16-26 Hz) of activated wakefulness. Relaxed

Sleep Medicine Clinics, 2010

ABSTRACT Insomnia is a disorder characterized by chronic difficulty with sleep and associated imp... more ABSTRACT Insomnia is a disorder characterized by chronic difficulty with sleep and associated impairments in daytime function. This article discusses diagnostic criteria as therapeutic targets for insomnia, self-medication, over-the-counter and prescription medications, and new therapeutic targets and approaches.

Sleep Medicine, 2001

Objectives and background: Given that non-selective gamma-aminobutyric acid (GABA) agonist hypnot... more Objectives and background: Given that non-selective gamma-aminobutyric acid (GABA) agonist hypnotics impair performance and potentiate the disruptive effects of ethanol, this study was done to determine the performance-impairing and ethanol-potentiating effects of zaleplon, a new selective GABA agonist hypnotic.Methods: Eighteen healthy men (12) and women (six), 31.5+/-5.6 years old, were studied. Each underwent six treatments of 2 days in duration, presented in a Latin square design with 2-12 recovery days between. The treatments were: placebo-placebo; placebo-ethanol; triazolam-placebo; triazolam-ethanol; zaleplon-placebo; and zaleplon-ethanol; with triazolam (0.25 mg) or placebo administered at 08:30 h, zaleplon (10 mg) or placebo at 09:00 h, and ethanol (0.75 g/kg) or placebo consumed from 09:30 h. Performance tests were completed each day at 10:30, 12:00 and 14:30 h.Results: Breath ethanol concentration (BrEC), tested 0.5, 2.0, 4.5 and 6 h post consumption, did not differ among treatments and peaked at 0.052%, declining to 0.037, 0.009 and 0.001%. Triazolam with and without ethanol impaired digit symbol substitution, symbol copying, simple and complex reaction times and divided attention performance relative to placebo-placebo treatment. It did so consistently at 10:30 and 12:00 h, and less consistently at 14:30 h. Zaleplon without ethanol impaired only digit symbol substitution and divided attention tracking, and only at 10:30 h. Zaleplon with ethanol impaired most measures at 10:30 and 12:00 h, but not at 14:30 h. Zaleplon without ethanol consistently differed from triazolam without ethanol in the extent of performance impairment. Zaleplon with ethanol began to differ from triazolam with ethanol in performance impairment on the 12:00 and 14:30 h test sessions. Ethanol itself impaired most measures at 10:30 h, fewer at 12:00 h and none at 14:30 h. All active drug treatments increased self-rated sleepiness compared with placebo-placebo. Triazolam without ethanol produced greater self-rated sleepiness than zaleplon without ethanol. The addition of ethanol to both drugs generally produced comparable levels of self-rated sleepiness.Conclusions: In an absolute sense, zaleplon produced less performance impairment and a shorter period of ethanol potentiation than triazolam.

Sleep Medicine, 2008

The preceding articles based on proceedings of The International Sleep Disorders Forum – The Art ... more The preceding articles based on proceedings of The International Sleep Disorders Forum – The Art of Good Sleep constitute a valuable contribution to the current knowledge base in this field. They also provide some stimulating and clear guidance on potential future research and clinical development required. The associations revealed between sleep and memory and learning processes are fascinating and will call for further research into the specific nature of the complex relationships between certain sleep states and certain memory processes. One of the key areas of current research is the development of more valid measures of sleep quality so that we can improve our evaluation of the management of sleep disorder patients. We have seen that there is much to be done in this area in developing valid sleep quality models, particularly in patients with comorbidities such as depression which further confound the self assessment of sleep quality. Obviously, there is much to be learned of the mechanisms for sleep disturbances in patients with depression and sleep disorders and, in these patients, relating sleep outcomes measures to the underlying neurobiology would appear to be a valid and productive approach. One of the largest groups of patients suffering from insomnia is the elderly. Not only do they have a greater prevalence of insomnia but they also experience more negative consequences associated with insomnia and are at greater risk for falls, possibly due both to the sleep disorder and to the medication prescribed. We can do more for this group of patients by individualizing the management and by increasing our awareness of the increased risk of falls due to inappropriate treatment. This will be aided by the availability of more clinical evidence on the impact of sleep and its treatment on falls, especially with regard to use of the newer non-benzodiazepine GABA receptor agonists in elderly patients. The observation that the effect of treatment on the risk of falls and fall risk factors (such as postural stability, balance, gait and reaction time) should be included as clinical endpoints in studies of sleep disorder treatments is pertinent given the challenges of treating this patient population. In conclusion, although there have been considerable advances in the development of outcome measures for sleep, sleep loss and insomnia presented and discussed at the Art of Good Sleep forum, there is much still to be learned. These papers provide us with some indication of the scope of future research in sleep outcomes, all of which will help to improve the quality of our clinical studies and will contribute to improvements in the management of sleep disorders.

Psychopharmacology, 1992

Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine w... more Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine whether or not rebound insomnia would increase the likelihood of self administering a benzodiazepine (triazolam 0°25 mg) hypnotic. The groups compared were patients with insomnia and disturbed sleep, insomnia and normal sleep, and healthy normals. Rebound insomnia, by both subjective and polysomnographic assessment, was induced. The experience of rebound insomnia did not increase the likelihood of self administering a benzodiazepine hypnotic in any of the groups. There were clear group differences in pill self administration with normals rarely and insomnia patients frequently, but not differentially (placebo versus active drug) self administering pills.

Psychopharmacology, 2011

Rationale Adverse drug effects such as reduced alertness may cause drivers to be unaware that the... more Rationale Adverse drug effects such as reduced alertness may cause drivers to be unaware that their driving is impaired. Objective This study was conducted to examine if drivers are adequately aware of their driving ability when treated with central nervous system drugs. Methods Data from three clinical trials applying the on-theroad driving test were used to compare the primary outcome measure, the Standard Deviation of Lateral Position, with subjective assessments of alertness before driving, as well as perceived driving quality, and mental effort to perform the test. Results The analyses revealed significant correlations for perceived driving quality (r=−0.498, p<0.0001), mental effort to perform the test (r= 0.408, p < 0.0001), and alertness taken before driving (r=−0.115, p<0.017). The predictive validity (R 2) of perceived driving quality (24.8%), mental effort (16.6%), and alertness before driving (1.3%) was low. Conclusion The analyses show that subjective assessments do not robustly relate to actual driving performance either in terms of judgments about alertness before the drive or ratings of performance after the drive.

Neuroscience Letters, 1981

The relationship of dream content to the immediate pre- and post-sleep mentation of the dreamer w... more The relationship of dream content to the immediate pre- and post-sleep mentation of the dreamer was studied using the electrophysiologically defined state of REM (rapid eye movement sleep) as dream collection time. The subjects were 20 male and 20 female volunteers, ages 18 to 25. Each slept for three non-consecutive nights in the laboratory and had REM awakenings and pre- and post-sleep verbal content collected. REM reports and waking verbal samples were scored on 18 Hall-Van de Castle content scales. The interscorer agreement of two judges was 0.90. Product moment correlations were performed on each of the 18 content categories between content of the REM reports and of the waking verbal samples. Across all 40 subjects, 9 out of 18 correlations were statistically significant and 14 of the 18 were positive. The zero-mu test indicated that the distribution of the 18 correlations was significantly different from zero. Thus it can be concluded that dream content is related to the psychological parameters of waking life, in a continuous rather than compensatory manner.

Journal of Clinical Sleep Medicine, 2007

port; and has participated in speaking engagements supported by Sanofi and Takeda. Dr. Scharf is ... more port; and has participated in speaking engagements supported by Sanofi and Takeda. Dr. Scharf is a member of Neurocrine Biosciences Insomnia Advisory Board. Dr. Lankford has served on the advisory board the speaker's bureau for Neurocrine Biosciences, Inc. Dr. Farber is employed by Neurocrine Biosciences. Inc. Dr. Rosenberg has indicated no other financial conflicts of interest.

Sleep, 1986

Performance measures were compared to the multiple sleep latency test (MSL T) as indices to asses... more Performance measures were compared to the multiple sleep latency test (MSL T) as indices to assess tolerance to the residual effects of benzodiazepine hypnotics during repeated nightly administration. Twelve healthy, normal sleepers received flurazepam 30 mg, temazepam 30 mg, and placebo for nine nights in a repeated measures, Latin-square design with 19 nights of recovery separating the treatments. As compared to placebo, both drugs altered sleep stage parameters in the early (nights 1-2) and late (nights 8-9) phases of the study. Hypnotic effects were found for both drugs in the early phase, but diminished for both in the late phase. The subjects' performance the next day was disrupted following treatment with flurazepam, but not with temazepam, during the early phase. Mean sleep latency on the MSLT was reduced by both drugs during the early phase. During the late phase, flurazepam did not disrupt performance but still affected the MSL T. Temazepam affected neither index the next day during the late phase.

Sleep Medicine, 2015

reported outcomes, total sleep time Role of the funding source: This study was funded by Organon,... more reported outcomes, total sleep time Role of the funding source: This study was funded by Organon, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ. Key individuals under the employment of Merck & Co., Inc. who were involved in the design and conduct of the study appear as authors on the manuscript, and were involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. HIGHLIGHTS  Esmirtazapine has a novel mechanism vs. other hypnotics (5-HT2A/H1 antagonist)  This 2-week outpatient study evaluated esmirtazapine vs. placebo in primary insomnia  Esmirtazapine significantly improved sleep onset, duration and quality vs. placebo  There was no evidence of rebound insomnia after discontinuation of esmirtazapine  Esmirtazapine was well tolerated; ≤7% of patients withdrew due to adverse events ABSTRACT Background: Esmirtazapine (Org 50081), a high-affinity antagonist at 5-HT 2A and H 1 receptors, was assessed for its hypnotic efficacy. Methods: In this double-blind, randomized study, non-elderly patients with primary insomnia (but otherwise healthy) were treated with esmirtazapine (1.5, 3.0, or 4.5 mg) or placebo for 2 weeks. The primary endpoint was patient-reported total sleep time (TST); other patient-reported endpoints included sleep latency (SL), wake time after sleep onset (WASO), number of awakenings, sleep quality, and satisfaction with sleep duration. Measures to assess the potential adverse effects of treatment included morning alertness, daytime function/napping, and rebound insomnia during a single-blind placebo run-out week after treatment ended. Adverse events (AEs) were also assessed. Results: Overall, 526 patients were randomized and 463 (88%) completed treatment. All esmirtazapine doses significantly improved TST, SL, sleep quality, and satisfaction with sleep duration versus placebo. Relative to placebo, TST was increased by 30-40 min and SL decreased by ~12 min for all doses. The highest dose (4.5 mg) also significantly reduced

Archiv der Pharmazie, 2014

A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones were prepared in se... more A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones were prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Whereas hydrazones derived from 3-benzoylpyridazines (IC 50 ¼ 0.99-8.74 mM) inhibited the proliferation of the tumor cell lines tested, the non-fully aromatic 3benzoylpyridazinone hydrazones (IC 50 > 10 mM) turned out to be inactive. Compounds E-1b (IC 50 ¼ 0.12 mM) and E-1d (IC 50 ¼ 0.18 mM) exert high cytotoxic activities in clonogenic assays involving human tumor cells of different tissue origins. In vivo application of compound E-1b (300 mg/kg/day) resulted in a 66% reduction in tumor burden.

Journal of Sleep Research, 2014

Review of Scientific Instruments, 2014

We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction ... more We have developed a pulsed magnet system with panoramic access for synchrotron x-ray diffraction in magnetic fields up to 31 T and at low temperature down to 1.5 K. The apparatus consists of a split-pair magnet, a liquid nitrogen bath to cool the pulsed coil, and a helium cryostat allowing sample temperatures from 1.5 up to 250 K. Using a 1.15 MJ mobile generator, magnetic field pulses of 60 ms length were generated in the magnet, with a rise time of 16.5 ms and a repetition rate of 2 pulses/hour at 31 T. The setup was validated for single crystal diffraction on the ESRF beamline ID06.

Sleep, 2014

To assess moderators, such as stressor chronicity, and mediators, including stress response in th... more To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Design: Longitudinal. Setting: Epidemiological. Participants: A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. Interventions: None. Measurements and Results: Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Conclusions: Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice.

Sleep, 2015

(AI), and sleepy insomniacs (SI). Measurements: Sleep parameters were assessed by sleep diary. Ci... more (AI), and sleepy insomniacs (SI). Measurements: Sleep parameters were assessed by sleep diary. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was measured using the multiple sleep latency test (MSLT). Brain activity was measured using the N1 event-related potential (ERP). A tandem repeat in PER3 was genotyped from saliva DNA. Results: (1) AI group showed normal MSLT scores but elevated N1 amplitudes indicating cortical hyperarousal. (2) SI group showed pathologically low MSLT scores but normal N1 amplitudes. (3) AI and SI groups were not significantly different from one another in circadian phase, while controls were significantly phase-delayed relative to both SWD groups. (4) AI showed significantly longer sleep latencies and lower sleep efficiency than controls during both nocturnal and diurnal sleep. SI significantly differed from controls in nocturnal sleep parameters, but differences during diurnal sleep periods were smaller and not statistically significant. (5) Genotype × phenotype χ 2 analysis showed significant differences in the PER3 VNTR: 9 of 10 shift workers reporting sleepiness in a post hoc genetic substudy were found to carry the long tandem repeat on PER3, while 4 of 14 shift workers without excessive sleepiness carried the long allele. Conclusions: Our results suggest that the sleepy insomnia phenotype is comprehensively explained by circadian misalignment, while the alert insomnia phenotype resembles an insomnia disorder precipitated by shift work.

Principles and Practice of Sleep Medicine, 2005

Physiology & Behavior, 2000

Study objectives: There is accumulating evidence that the common cold produces impairments in psy... more Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300 ± 0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3 ± 5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.

2013 IEEE 39th Photovoltaic Specialists Conference (PVSC), 2013

ABSTRACT Excess-carrier recombination lifetime is a key parameter in silicon solar cell design an... more ABSTRACT Excess-carrier recombination lifetime is a key parameter in silicon solar cell design and production. With the vast international use and recent standardization (SEMI PV13) of eddy-current wafer and brick silicon lifetime test instruments, it is important to quantify the inter- and intralaboratory repeatability. This paper presents the results of an international interlaboratory study conducted with 24 participants to determine the precision of the SEMI PV13 eddy-current carrier lifetime measurement test method. Overall, the carrier recombination lifetime between-laboratory reproducibility was found to be within ±11% for the quasi-steady-state mode and ±8% for transient mode for wafer samples, and within ±4% for bulk samples.

Traffic Injury Prevention, 2014

Sleep Medicine Clinics, 2010

Polysomnographic (PSG) studies, which refers to the simultaneous recording of multiple electrophy... more Polysomnographic (PSG) studies, which refers to the simultaneous recording of multiple electrophysiological parameters [i.e., electrooculogram (EOG), electromyogram (EMG), and electroencephalogram (EEG)] during sleep, have demonstrated that sleep is a complex, highly organized biological state composed of two distinct brain states, rapid eye movement (REM) and non rapid eye movement (NREM) sleep (1,2). In terms of EEG activity, NREM sleep is characterized by EEG slowing and increased voltage relative to the low voltage (10-30 microvolts) and fast frequency (16-26 Hz) of activated wakefulness. Relaxed

Sleep Medicine Clinics, 2010

ABSTRACT Insomnia is a disorder characterized by chronic difficulty with sleep and associated imp... more ABSTRACT Insomnia is a disorder characterized by chronic difficulty with sleep and associated impairments in daytime function. This article discusses diagnostic criteria as therapeutic targets for insomnia, self-medication, over-the-counter and prescription medications, and new therapeutic targets and approaches.

Sleep Medicine, 2001

Objectives and background: Given that non-selective gamma-aminobutyric acid (GABA) agonist hypnot... more Objectives and background: Given that non-selective gamma-aminobutyric acid (GABA) agonist hypnotics impair performance and potentiate the disruptive effects of ethanol, this study was done to determine the performance-impairing and ethanol-potentiating effects of zaleplon, a new selective GABA agonist hypnotic.Methods: Eighteen healthy men (12) and women (six), 31.5+/-5.6 years old, were studied. Each underwent six treatments of 2 days in duration, presented in a Latin square design with 2-12 recovery days between. The treatments were: placebo-placebo; placebo-ethanol; triazolam-placebo; triazolam-ethanol; zaleplon-placebo; and zaleplon-ethanol; with triazolam (0.25 mg) or placebo administered at 08:30 h, zaleplon (10 mg) or placebo at 09:00 h, and ethanol (0.75 g/kg) or placebo consumed from 09:30 h. Performance tests were completed each day at 10:30, 12:00 and 14:30 h.Results: Breath ethanol concentration (BrEC), tested 0.5, 2.0, 4.5 and 6 h post consumption, did not differ among treatments and peaked at 0.052%, declining to 0.037, 0.009 and 0.001%. Triazolam with and without ethanol impaired digit symbol substitution, symbol copying, simple and complex reaction times and divided attention performance relative to placebo-placebo treatment. It did so consistently at 10:30 and 12:00 h, and less consistently at 14:30 h. Zaleplon without ethanol impaired only digit symbol substitution and divided attention tracking, and only at 10:30 h. Zaleplon with ethanol impaired most measures at 10:30 and 12:00 h, but not at 14:30 h. Zaleplon without ethanol consistently differed from triazolam without ethanol in the extent of performance impairment. Zaleplon with ethanol began to differ from triazolam with ethanol in performance impairment on the 12:00 and 14:30 h test sessions. Ethanol itself impaired most measures at 10:30 h, fewer at 12:00 h and none at 14:30 h. All active drug treatments increased self-rated sleepiness compared with placebo-placebo. Triazolam without ethanol produced greater self-rated sleepiness than zaleplon without ethanol. The addition of ethanol to both drugs generally produced comparable levels of self-rated sleepiness.Conclusions: In an absolute sense, zaleplon produced less performance impairment and a shorter period of ethanol potentiation than triazolam.

Sleep Medicine, 2008

The preceding articles based on proceedings of The International Sleep Disorders Forum – The Art ... more The preceding articles based on proceedings of The International Sleep Disorders Forum – The Art of Good Sleep constitute a valuable contribution to the current knowledge base in this field. They also provide some stimulating and clear guidance on potential future research and clinical development required. The associations revealed between sleep and memory and learning processes are fascinating and will call for further research into the specific nature of the complex relationships between certain sleep states and certain memory processes. One of the key areas of current research is the development of more valid measures of sleep quality so that we can improve our evaluation of the management of sleep disorder patients. We have seen that there is much to be done in this area in developing valid sleep quality models, particularly in patients with comorbidities such as depression which further confound the self assessment of sleep quality. Obviously, there is much to be learned of the mechanisms for sleep disturbances in patients with depression and sleep disorders and, in these patients, relating sleep outcomes measures to the underlying neurobiology would appear to be a valid and productive approach. One of the largest groups of patients suffering from insomnia is the elderly. Not only do they have a greater prevalence of insomnia but they also experience more negative consequences associated with insomnia and are at greater risk for falls, possibly due both to the sleep disorder and to the medication prescribed. We can do more for this group of patients by individualizing the management and by increasing our awareness of the increased risk of falls due to inappropriate treatment. This will be aided by the availability of more clinical evidence on the impact of sleep and its treatment on falls, especially with regard to use of the newer non-benzodiazepine GABA receptor agonists in elderly patients. The observation that the effect of treatment on the risk of falls and fall risk factors (such as postural stability, balance, gait and reaction time) should be included as clinical endpoints in studies of sleep disorder treatments is pertinent given the challenges of treating this patient population. In conclusion, although there have been considerable advances in the development of outcome measures for sleep, sleep loss and insomnia presented and discussed at the Art of Good Sleep forum, there is much still to be learned. These papers provide us with some indication of the scope of future research in sleep outcomes, all of which will help to improve the quality of our clinical studies and will contribute to improvements in the management of sleep disorders.

Psychopharmacology, 1992

Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine w... more Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine whether or not rebound insomnia would increase the likelihood of self administering a benzodiazepine (triazolam 0°25 mg) hypnotic. The groups compared were patients with insomnia and disturbed sleep, insomnia and normal sleep, and healthy normals. Rebound insomnia, by both subjective and polysomnographic assessment, was induced. The experience of rebound insomnia did not increase the likelihood of self administering a benzodiazepine hypnotic in any of the groups. There were clear group differences in pill self administration with normals rarely and insomnia patients frequently, but not differentially (placebo versus active drug) self administering pills.

Psychopharmacology, 2011

Rationale Adverse drug effects such as reduced alertness may cause drivers to be unaware that the... more Rationale Adverse drug effects such as reduced alertness may cause drivers to be unaware that their driving is impaired. Objective This study was conducted to examine if drivers are adequately aware of their driving ability when treated with central nervous system drugs. Methods Data from three clinical trials applying the on-theroad driving test were used to compare the primary outcome measure, the Standard Deviation of Lateral Position, with subjective assessments of alertness before driving, as well as perceived driving quality, and mental effort to perform the test. Results The analyses revealed significant correlations for perceived driving quality (r=−0.498, p<0.0001), mental effort to perform the test (r= 0.408, p < 0.0001), and alertness taken before driving (r=−0.115, p<0.017). The predictive validity (R 2) of perceived driving quality (24.8%), mental effort (16.6%), and alertness before driving (1.3%) was low. Conclusion The analyses show that subjective assessments do not robustly relate to actual driving performance either in terms of judgments about alertness before the drive or ratings of performance after the drive.

Neuroscience Letters, 1981

The relationship of dream content to the immediate pre- and post-sleep mentation of the dreamer w... more The relationship of dream content to the immediate pre- and post-sleep mentation of the dreamer was studied using the electrophysiologically defined state of REM (rapid eye movement sleep) as dream collection time. The subjects were 20 male and 20 female volunteers, ages 18 to 25. Each slept for three non-consecutive nights in the laboratory and had REM awakenings and pre- and post-sleep verbal content collected. REM reports and waking verbal samples were scored on 18 Hall-Van de Castle content scales. The interscorer agreement of two judges was 0.90. Product moment correlations were performed on each of the 18 content categories between content of the REM reports and of the waking verbal samples. Across all 40 subjects, 9 out of 18 correlations were statistically significant and 14 of the 18 were positive. The zero-mu test indicated that the distribution of the 18 correlations was significantly different from zero. Thus it can be concluded that dream content is related to the psychological parameters of waking life, in a continuous rather than compensatory manner.