This is the final year of this directed research project. This year's aims were reduced due to an unexpected funding reduction. The reduced aims were:

1) Continue the three-day inpatient study of narrowband blue solid state light on alertness and cognitive performance: (a). complete neurocognitive and melatonin data analysis (b). initiate analysis of polysomnography data, completing as much as possible with remaining funds.

2) Complete a pilot study on testing the effect of light emitting surface size on melatonin suppression. (a). finish running subjects through the test conditions (b). complete blood assays and data analysis.

3) Write a report on the results on items 1 and 2 above.

Two studies have been previously completed for this project using two prototype 122 cm x 122 cm solid-state blue light (peak wavelength 469 nm) exposure systems. A melatonin suppression study has resulted in a peer-reviewed manuscript published in the Journal of Applied Physiology (West et al., 2011). The second study was a three-day inpatient study on the effects of narrowband blue light from light emitting diodes (LEDs) on alertness and cognitive performance.

Per the first aim above, plasma melatonin, alertness, and neurocognitive performance measures have been analyzed. Polysomnographic data from Karolinska Drowsiness Tests (KDTs) was analyzed from 8 of the 22 subjects. Further KDT analysis was not feasible due to the unexpected funding cut. Two presentations were made at international meetings describing the protocol and the preliminary analysis of the melatonin data set (Hanifin et al., 2010a, 2010b). The completed melatonin, alertness, and neurobehavioral data sets are now being written up as a chapter in a doctoral thesis (Hanifin, unpublished) and subsequently are likely to be published as a peer-review manuscript. Importantly, the experimental 122 cm x 122 cm LED light panels we have used in the first two studies for this project are too large to be flight-worthy, although they could be used for lighting countermeasures for ground crew.

This year's second aim was concerned with testing the consequences of reducing the size of the light-emitting surface to a more flight-worthy size. This pilot study used the acute melatonin suppression response as its dependent variable for quantifying how different size light-emitting surfaces influence this neuroendocrine response. A pilot study protocol was designed and approved by the Jefferson Institutional Review Board (IRB). Two new exposure systems were designed, constructed, and equipped with blue-enriched broad-bandwidth LEDs (6,500 K) for this study. Of note, this blue-enriched LED light source is similar to one of the LED sources being specified for the Solid-State Light Assembly (SSLA) that is being proposed for replacing the current fluorescent General Luminaire Assemblies (GLA) onboard the International Space Station. Eight healthy male and female subjects were recruited, screened, and enrolled in an experiment that employed a within-subjects design. Subjects were seated comfortably with their head resting in an ophthalmologic head holder facing the light source at a distance of 90 cm. The volunteers' pupils were freely reactive during the light exposure that was given between 2:00 and 3:30 AM. Subjects were exposed to a 122 cm x 122 cm exposure area or a much smaller 3.81 cm x 3.81 cm exposure area at an equal surface irradiance and a dark control exposure (with at least one week between each exposure). The volunteers have completed all 24 study nights and their plasma samples have been quantified for plasma melatonin content. The resultant data support the hypothesis that light source size is a critical factor in the design of SSLA lighting that can be used to serve as an in-flight countermeasure for circadian disruption and sleep during long duration space exploration. A follow up study testing a range of light emitting surface sizes including the surface size of the SSLA (approximately 11 cm x 54 cm) was planned but not initiated due to the unexpected funding cut. The ultimate goal from this work is to develop a lighting countermeasure that enhances alertness and cognitive performance in ground crew members and astronauts.

This year's results ultimately will impact the NASA Human Integration Design Handbook and the Space Flight Human Systems Standard, NASA-STD-3001, that provide guidance for supporting crew health, habitability, environment, and human factors in human space flight. Our progress addresses NASA Human Research Program Integrated Risk Plan (2011) risk area 22 (Sleep 5, 9, and 10) Critical Risk areas. These areas concern countermeasures that will optimally mitigate health, performance and safety problems due to circadian, neuroendocrine, and neurobehavioral disruption, for flight, surface, and ground crews.

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination, and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. Many people also experience the same effects after air travel across several time zones. The impact of these deficits affects many industries, including transportation, manufacturing, communications, medicine, and homeland security. It has long been a source of concern for the military, as well. In the past, the U.S. Air Force has supported our laboratory to study the acute alerting effects of light (French et al., 1990; Brainard et al., 1996). Our past work for NIH (National Institute of Health) has continued this effort (Lockley et al., 2006).

Existing therapeutic lighting interventions stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation (Byrne and Brainard, 2012). A more efficient intervention with increased potency and/or fewer side effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD). It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, sSAD (Lam and Levitt, 1999). Similar bright white light interventions also are used to treat jetlag. Side effects from exposure to bright white light for these and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity and, potentially, with fewer side effects. Our group has completed Phase I testing of light therapy with blue solid-state lighting for patients with SAD (Glickman et al., 2006).

A melatonin suppression study was conducted with the narrow bandwidth blue LED units to characterize their biological potency and to guide the selection of the light intensity for the multiday alertness study. Healthy subjects (N=8) completed a total of 84 nighttime melatonin suppression experiments. Data analysis was completed showing that the blue LED light evokes a dose-response melatonin suppression, and permitting the calculation of a target intensity for the alertness study. The data also indicate that blue LED light is stronger than 4,000 K white fluorescent light for suppressing melatonin. A peer-review manuscript has been published on these results (West et al., 2011).

Over 300 individuals volunteered to be screened for a 3-day alertness study with the blue LED light units. From that pool of volunteers, 26 subjects completed all medical, psychological, and ophthalmological examinations as well as screens for stability of sleep-wake cycles and drugs of abuse. Of the 24 subjects that entered the study, 22 completed the three-day inpatient alertness protocol. Analysis of plasma melatonin, subjective alertness, objective alertness, and neurobehavioral data was finalized this year. Due to reduced funding, only a partial analysis of polysomnography data was completed. Two presentations have been made at international meetings describing the protocol and a partial analysis of the resultant data set (Hanifin et al., 2010a, 2010b). Preliminary testing of visual performance and color discrimination has been done with selected intensities of the narrow bandwidth blue LEDs with 8 healthy subjects. A pilot study on the consequences of reducing the size of the light-emitting surface to a more flight-worthy size was designed and approved by the Jefferson IRB. Two exposure systems with broad-bandwidth blue-enriched LEDS (6,500 K) were used for this study. Eight healthy male and female subjects completed all 24 nighttime experiments for this study.

This is the fifth year of a directed research project. This past year, we have worked on the following seven aims:

1) Publish a peer-review manuscript on the blue solid-state light melatonin suppression bench-marking study.

2) Complete enrolling subjects for the first alertness and cognitive performance study.

3) Complete assay of alertness study samples for melatonin.

4) Do preliminary analysis of polysomnography, subjective and objective alertness, and neurobehavioral test data from the alertness study.

5) Develop a pilot study design on the consequences of reducing the size of the light-emitting surface to a more flight-worthy size and submit a study protocol for Jefferson IRB review.

6) Related to aim 5, design the necessary solid-state light source exposure systems for the pilot study.

7) Related to aim 5, screen, recruit and enter subjects into the pilot study.

During the first four years of this project, we made significant progress in 1) creating two prototype 122 sq cm solid-state blue light (peak wavelength 469 nm) exposure systems for the studies, 2) validating the safety of these prototypes by an independent hazard analysis that met federal (ACGIH), international (ICNIRP), and NASA guidelines for safety of human ocular exposure, and 3) completing a bench-marking melatonin suppression study using the blue light prototype with eight healthy subjects. The melatonin study confirmed that narrowband, polychromatic blue solid-state light suppresses melatonin in healthy subjects in a dose-response manner and enabled the calculation of a target intensity for the initial alertness study.

In terms of the first aim for the past year, we published a peer reviewed manuscript on the blue solid-state light melatonin suppression bench-marking study in the Journal of Applied Physiology (West, 2011).

The second, third and fourth aims are concerned with our first study on the effects of narrowband, polychromatic blue solid-state light on alertness and cognitive performance in healthy male and female subjects. Over 300 individuals volunteered to be screened for the first 3-day alertness study with the blue LED light units. From that pool of volunteers, 26 subjects completed all medical, psychological, and ophthalmological examinations as well as screens for stability of sleep-wake cycles and drugs of abuse. Of the 24 subjects that entered study, 22 completed the three-day inpatient alertness protocol. Analysis of plasma melatonin, subjective alertness, objective alertness, and neurobehavioral data will be finalized this year. Analysis of polysomnography data is in process. Two presentations have been made at international meetings describing the protocol the preliminary data (Hanifin et al., 2010a, 2010b; Ed. note: see FY2010 Task Book Bibliography). Preliminary testing of visual performance and color discrimination has been done with selected intensities of the narrow bandwidth blue LEDs with 8 healthy subjects.

It is important to note that the experimental 122 sq cm LED light panels we have used in the first two studies are too large to be flight-worthy. The fifth, sixth, and seventh aims are concerned with testing the consequences of reducing the size of the light-emitting surface to a more flight-worthy size. The initial pilot study uses the acute melatonin suppression response as its dependent variable for quantifying how different size light-emitting surfaces influence this neuroendocrine response. A pilot study protocol has been designed and approved by the Jefferson IRB. Two new exposure systems have been designed, constructed, and equipped with blue-enriched broad-bandwidth LEDS (6,500 K) for this study. Importantly, this blue-enriched LED light source is similar to one of the LED sources being specified for the Solid-State Light Assembly (SSLA) that is being proposed for retrofitting the current fluorescent General Light Assembly (GLA) onboard the International Space Station. Subject recruitment, screening and enrollment has been initiated. To date, subjects have completed more than 10 study nights for this ongoing study.

The ultimate goal is to develop a lighting countermeasure that enhances alertness and cognitive performance in ground crew members and astronauts. This year's results will impact the NASA Human Integration Design Handbook and the Space Flight Human Systems Standard, NASA-STD-3001, that provide guidance for supporting crew health, habitability, environment, and human factors in human space flight. Our progress addresses NASA Human Research Program Integrated Risk Plan (2010) risk area 22 (Sleep 5, 9, and 10) Critical Risk areas. These areas concern countermeasures that will optimally mitigate performance problems associated with sleep loss and circadian disturbances and the "mismatch between crew physical capabilities and task demands."

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. Many people also experience the same effects after air travel across several time zones. The impact of these deficits affects many industries, including transportation, manufacturing, communications, medicine, and homeland security. It has long been a source of concern for the military, as well. In the past, the U.S. Air Force has supported our laboratory to study the acute alerting effects of light (French et al., 1990; Brainard et al., 1996). Our current work for NIH has continued this effort (Lockley et al., 2006).

Existing therapeutic lighting interventions stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation. A more efficient intervention with increased potency and/or fewer side effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD), also known as winter depression. It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, subsyndromal Seasonal Affective Disorder (sSAD) (Lam and Levitt, 1999). Similar bright white light interventions also are used to treat jetlag. Side effects from exposure to bright white light for these and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity and, potentially, with fewer side effects. Our group has completed Phase I testing of light therapy with blue solid-state lighting for patients with SAD (Glickman et al., 2006).

For this project, we have four 122 sq cm solid-state light sources: two with narrow-bandwidth (peak 469 nm) LEDs and two with broad-bandwidth blue-enriched LEDS that emit white-appearing light with a CCT of 6,500 K. These units provide a large, uniform light-emitting surface with intensity modulation. An independent safety analysis of both LED light sources based on national (ACGIH) and international (ICNIRP) criteria has been completed. James Maida of JSC and Charles Bowen, Ph.D., of Lockheed Martin (retired) have confirmed that the blue LED units meet NASA's safety standards (West et al., 2008).

An initial melatonin suppression study was conducted with the narrow bandwidth blue LED units to characterize their biological potency and to guide the selection of the light intensity for the first alertness study. Healthy subjects (N>=8) completed a total of 84 nighttime melatonin suppression experiments. Data analysis was completed permitting the calculation of a target intensity for the alertness study. The data showed that the blue LED light evokes a dose-response melatonin suppression. The data also indicate that blue LED light is stronger than 4,000 K white fluorescent light for suppressing melatonin. A peer-reviewed manuscript has been published on these results (West, 2011).

Over 300 individuals volunteered to be screened for the first 3-day alertness study with the blue LED light units. From that pool of volunteers, 26 subjects completed all medical, psychological, and ophthalmological examinations as well as screens for stability of sleep-wake cycles and drugs of abuse. Of the 24 subjects that entered study, 22 completed the three-day inpatient alertness protocol. Analysis of plasma melatonin, subjective alertness, objective alertness, and neurobehavioral data will be finalized this year. Analysis of polysomnography data is in process. Two presentations have been made at international meetings describing the protocol and a partial analysis of the melatonin data set (Hanifin et al., 2010a, 2010b; Ed. note: see FY2010 Task Book Bibliography). Preliminary testing of visual performance and color discrimination has been done with selected intensities of the narrow bandwidth blue LEDs with 8 healthy subjects.

A pilot study protocol on the consequences of reducing the size of the light-emitting surface to a more flight-worthy size has been designed and approved by the Jefferson IRB. Two exposure systems with broad-bandwidth blue-enriched LEDS (6,500 K) are being used for this study. Subject recruitment, screening and enrollment has been initiated. To date, subjects have completed more than 10 study nights for this ongoing study.

1) Submit a peer-review manuscript on the blue solid-state light melatonin suppression bench-marking study.

2) Continue enrolling subjects for the first study on alertness and cognitive performance.

3) Assay samples from the ongoing alertness study for melatonin.

4) Do preliminary analysis of polysomnography, subjective and objective alertness, and neurobehavioral test data from the ongoing alertness study.

5) Develop a study design on the consequences of reducing the size of the light emitting surface to a more flight-worthy size.

6) Submit a protocol on the new study design for Jefferson IRB review.

7) Related to aims 5 and 6, a) design and acquire new prototype solid-state light sources, or b) modify the current study light sources.

During the first three years of this project, we made significant progress in 1) creating two prototype 122 sq cm solid-state blue light (peak wavelength 475 nm) exposure systems for the studies, 2) validating the safety of these prototypes by an independent hazard analysis that met federal (ACGIH), international (ICNIRP), and NASA guidelines for safety of human ocular exposure, and 3) completing a bench-marking melatonin suppression study using the blue light prototype with eight healthy subjects. The melatonin study confirmed that narrowband, polychromatic blue solid-state light suppresses melatonin in healthy subjects in a dose-response manner and enabled the calculation of a target intensity for the initial alertness study.

In terms of the first aim for the past year, we completed data analysis of the bench-marking blue solid-state light melatonin suppression study and submitted a peer-review manuscript on the results. Subsequently we have received reviews that are generally positive. The co-authors are currently working on a manuscript revision.

The second, third and fourth aims are concerned with our first study on the effects of narrowband, polychromatic blue solid-state light on alertness and cognitive performance in healthy male and female subjects. To date, over 300 individuals inquired about participating and went through initial elements of screening for the first 3-day alertness study. From that pool of interested volunteers, 26 subjects completed all medical, psychological, and ophthalmological examinations as well as screens for stability of sleep-wake cycles and drugs of abuse. Of the 24 subjects that entered study, 22 completed the three-day inpatient alertness protocol. Preliminary analysis of plasma melatonin, subjective alertness, objective alertness, polysomnography, and neurobehavioral data are now in process and will continue well into the next year. Until this data analysis is completed, no further volunteers will be screened or entered into the protocol. Two presentations have been made at international meetings describing the protocol and a partial analysis of the melatonin data set (Hanifin et al., 2010a, 2010b).

It is important to note that the experimental 122 sq cm LED light panels we have used in the first two studies, are too large to be flight-worthy. The fifth, sixth, and seventh aims are concerned with needing to test the consequences of reducing the size of the light-emitting surface to a more flight-worthy size. This study will use the acute melatonin suppression response as its dependent variable for quantifying how different size light-emitting surfaces influence this neuroendocrine response. A set of six different study designs were initially developed to test the relative efficacy of smaller light-emitting surfaces. The LRP staff met to review those study designs with the intent of selecting a single design to best accomplish this objective. Progress has been delayed, however, in finalizing this protocol due to unexpected, emergent work on the Solid-State Light Assembly (SSLA) that is being proposed for retrofitting the current fluorescent General Light Assembly (GLA) onboard the International Space Station. Given that the light-emitting surface dimensions of SSLA are now relatively certain, we are re-formulating our approach to include the SSLA light-emitting surface dimension in our overall study design. Instead of developing a new IRB application, we have been guided to amend an existing IRB protocol for supporting this study. This month we submitted that designated IRB for renewal and plan to develop the necessary amendments once the renewal application has been accepted. We have also determined that we will not need to acquire new solid-state light sources for this project. One or more of our current solid-state panels can be modified for the purpose of this study.

The ultimate goal is to develop a lighting countermeasure that enhances alertness and cognitive performance in ground crew members and astronauts. This year's results will impact the NASA Human Integration Design Handbook and the Space Flight Human Systems Standard, NASA-STD-3001, that provide guidance for supporting crew health, habitability, environment, and human factors in human space flight. Our progress addresses NASA Human Research Program Integrated Risk Plan (2009) risk areas 13, 33, and 76, and risk areas 26, 27, and 44 in the Bioastronautics Roadmap (2005).

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. Many people also experience the same effects after air travel across several time zones. The impact of these deficits affects many industries, including transportation, manufacturing, communications, medicine, and homeland security. It has long been a source of concern for the military, as well. In the past, the U.S. Air Force has supported our laboratory to study the acute alerting effects of light (French et al., 1990; Brainard et al., 1996). Our current work for NIH has continued this effort (Lockley et al., 2006).

Existing therapeutic lighting interventions stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation. A more efficient intervention with increased potency and/or fewer side effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD), also known as winter depression. It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, subsyndromal Seasonal Affective Disorder (sSAD) (Lam and Levitt, 1999). Similar bright white light interventions also are used to treat jetlag. Side effects from exposure to bright white light for these and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity and, potentially, with fewer side effects. Our group has completed Phase I testing of light therapy with blue solid-state lighting for patients with SAD (Glickman et al., 2006).

For this study, we have two identical 122 sq cm solid-state blue light sources, installed into identical exposure stations. Each light source consists of an array of 5,776 blue LEDs (peak 475 nm). These units provide a large, uniform light-emitting surface with intensity modulation. The light sources were developed collaboratively with Apollo Health, an NSBRI Industrial Partner. David Sliney, Ph.D., has completed an independent safety analysis of the blue LED light sources based on national (ACGIH) and international (ICNIRP) criteria. After reviewing Dr. Sliney's final report, James Maida of JSC and Charles Bowen, Ph.D., of Lockheed Martin confirmed that the units meet NASA's safety standards and co-authored with our team an abstract showing the safety evaluation results (West et al., 2008).

An initial melatonin suppression study was conducted to characterize the biological potency of the prototype light units and to guide the selection of the light intensity for the first alertness study. Eight healthy men and women participated in the study, completing a total of 84 nighttime melatonin suppression experiments. Data analysis has been completed and, based on the results, a target intensity for the alertness study was calculated. The data showed that the blue LED light evokes a dose-response melatonin suppression in healthy subjects. The data also indicate that blue LED light may be stronger than 4,000 K white fluorescent light for suppressing melatonin. We completed a manuscript on these results and submitted it for peer review. Subsequently we have received reviews that are generally positive. The co-authors are currently working on a manuscript revision.

To date, over 300 individuals contacted our program and went through initial elements of screening for the first 3-day alertness study. From that pool of interested volunteers, 26 subjects completed all medical, psychological, and ophthalmological examinations as well as screens for stability of sleep-wake cycles and drugs of abuse. Of the 24 subjects that entered study, 22 completed the three-day inpatient alertness protocol. Preliminary analysis of plasma melatonin, subjective alertness, objective alertness, polysomnography, and neurobehavioral data are now in process and will continue well into the next year. Until this data analysis is completed, no further volunteers will be screened or entered into the protocol. Two presentations have been made at international meetings describing the protocol and a partial analysis of the melatonin data set (Hanifin et al., 2010a, 2010b).

This is the third year of a directed research project. This past year, we have worked on the following seven aims:

1) Complete data analysis for the blue-enriched solid-state light melatonin suppression bench-marking study.

2) Present the melatonin study results at the NASA Investigators Workshop and complete a manuscript for publication.

3) Complete the setup, calibration, and staff training on polysomnographic equipment and performance testing batteries.

4) Secure necessary amendments to the approved IRB document for the first alertness study.

5) Recruit, screen, enroll, and begin running subjects for the first study on alertness and cognitive performance.

6) Identify follow-up studies.

7) As necessary, a) design and acquire new prototype solid-state light sources or b) develop modifications of current light sources for future studies.

During the first two years of this project, we made significant progress in 1) creating two prototype 122 x 122 cm solid-state blue light (475 nm) exposure systems for the studies, 2) validating the safety of these prototypes by an independent hazard analysis that met federal (ACGIH), international (ICNIRP), and NASA guidelines for safety of human ocular exposure, and 3) completing a bench-marking melatonin suppression study using the blue light prototype with eight healthy subjects.

In terms of the first aim for the past year, we completed data analysis of the bench-marking melatonin suppression study. The goals of the study were to characterize the biological potency of the prototype light units and guide the selection of the light intensity to be tested in the first alertness study. The data confirm that narrowband, polychromatic blue solid-state light suppresses melatonin in healthy subjects in a dose-response manner. Further, the data enabled the calculation of a target intensity for the first alertness study.

For the second aim, the melatonin suppression data was presented at the NASA Investigators' Workshop (West et al., 2008) and a first draft of a manuscript on the study has been completed. Revision of the manuscript by all co-authors is continuing. The intent is to submit a final manuscript to a peer-review journal during this coming year.

The third and fourth aims are concerned with our first study on the effects of narrowband, polychromatic blue solid-state light on alertness and cognitive performance in healthy male and female subjects. Although the collaborative team completed the design of this study in the prior year, further protocol modifications were necessary, and Jefferson’s IRB has approved 4 separate protocol revisions since then. In parallel, we established the polysomnography (PSG) and behavioral testing techniques for this project, and LRP staff completed the necessary training for using these methods. Erin Evans, a Registered PSG Technician at Brigham and Women’s Hospital, joined our team as a collaborator to assist with troubleshooting our PSG setup, data analysis, and data interpretation.

Progress on our fifth aim includes subject recruitment and participation in the alertness study. To date, over 170 individuals have applied to participate and have gone through initial steps of screening for the study. From that pool, more than 10 subjects have completed medical, psychological, and ophthalmological examinations, as well as screens for stability of sleep-wake cycles and drugs of abuse. Ten subjects have now completed the three-day inpatient alertness protocol. Preliminary analysis of plasma melatonin, subjective alertness, objective alertness, and neurobehavioral data are now in process. We plan to continue screening volunteers and entering eligible subjects into the protocol in the coming year.

In terms of our sixth and seventh aims, it is important to note that the experimental panel we currently are testing is not flight-worthy. A set of six different study designs has been developed to test the relative efficacy of smaller light emitting surfaces. The LRP staff has met to review these study designs with the intent of selecting a single design to best accomplish this objective. Although the details of the study design are not finalized, preliminary work on an IRB submission has been initiated. Preliminary discussions have addressed how to modify of the 122 x 122 cm exposure panels for the new study. Work on study design, exposure panel reconfiguration, and the associated IRB will continue into the coming year.

The ultimate goal of this project is to develop a lighting countermeasure that enhances alertness and cognitive performance. This year’s progress addresses Critical Risk areas 26 and 27 in the Bioastronautics Roadmap (research questions 26f, 26h, 27b, and 27f). These areas concern countermeasures that mitigate performance problems due to sleep loss and circadian disturbances. This work ultimately impacts Critical Risk 44 concerning the “mismatch between crew physical capabilities and task demands” (question 44f).

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. Many people also experience the same effects after air travel across several time zones. The impact of these deficits affects many industries, including transportation, manufacturing, communications, medicine, and homeland security. It has long been a source of concern for the military, as well. In the past, the U.S. Air Force has supported our laboratory to study the acute alerting effects of light (French et al., 1990; Brainard et al., 1996). Our current work for NIH has continued this effort (Lockley et al., 2006).

Existing therapeutic lighting interventions stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation. A more efficient intervention with increased potency and/or fewer side effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD), also known as winter depression. It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, subsyndromal Seasonal Affective Disorder (sSAD) (Lam and Levitt, 1999). Similar bright white light interventions also are used to treat jetlag. Side effects from exposure to bright white light for these and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity and, potentially, with fewer side effects. Our group has completed Phase I testing of light therapy with blue solid-state lighting for patients with SAD (Glickman et al., 2006).

For this study, we have two identical 122 x 122 cm solid-state blue light sources, installed into identical exposure stations. Each light source consists of an array of 5,776 blue LEDs (peak 475 nm). These units provide a large, uniform light-emitting surface with intensity modulation. The light sources were designed and developed collaboratively with Apollo Health, an NSBRI Industrial Partner. David Sliney, Ph.D., has completed an independent safety analysis of the blue LED light sources based on national (ACGIH) and international (ICNIRP) criteria. After reviewing Dr. Sliney’s final report, James Maida of JSC and Charles Bowen, Ph.D., of Lockheed Martin confirmed that the units meet NASA’s safety standards and were co-authors with our team on an abstract showing the safety evaluation results (West et al., 2008).

The aims of this bench-marking melatonin suppression study were to characterize the biological potency of the prototype light units and to guide the selection of the light intensity to be tested in the first alertness study. Eight healthy men and women participated in the study, completing a total of 84 nighttime melatonin suppression experiments. Data analysis has been completed and, based on the results, a target intensity for the first alertness study was calculated. The data also showed that the blue LED light evokes a dose-response melatonin suppression in healthy subjects. A first draft of a manuscript on these results has been completed. Revisions of the manuscript by all co-authors will continue into year 4 of work.

Although the collaborative team completed the design of our first study on the effect of blue solid-state light on alertness and cognitive performance in the prior year, further protocol modifications were implemented, and Jefferson’s IRB has approved 4 separate protocol revisions since then. In parallel, we established the polysomnography and behavioral testing techniques for this project and LRP staff completed the necessary training for using these methods. To date, over 170 individuals have applied to participate and have gone through initial elements of screening for the alertness study. From that pool, more than 10 subjects have completed medical, psychological, and ophthalmological examinations, as well as screens for stability of sleep-wake cycles and drugs of abuse. Ten subjects have now completed the three-day inpatient alertness protocol. Preliminary analysis of plasma melatonin, subjective alertness, objective alertness, and neurobehavioral data are now in process. We plan to continue screening volunteers and entering eligible subjects into the protocol in the coming year.

This is the second year of a new, directed research project. This past year, we have worked on the following seven aims:

1) Have independent safety analysis completed on the new solid-state lighting prototype and involve lighting engineers from Johnson Space Center (JSC) and Lockheed Martin in reviewing and approving the safety analysis and proposing any further assessments to ensure that the prototype meets NASA’s standards and applications.

2) Acquire a second solid state blue light exposure system from Apollo Light Systems, Inc., an NSBRI industrial partner. Install and characterize the second system prior to its implementation in the melatonin bench-marking studies.

3) Complete human subject recruitment and nighttime experiments for the melatonin suppression bench-marking study with blue solid-state light. Complete assay of melatonin samples and begin data analysis for this study.

4) Complete the design of the inaugural study on the effect of blue solid-state light on alertness and cognitive performance in healthy subjects.

5) Write and secure Institutional Review Board (IRB) approval of the first alertness study design.

6) Set up and calibrate polysomnographic equipment. Train staff in use of polysomnographic equipment and performance testing batteries for assessing alertness and cognitive performance in the study volunteers.

7) Recruit and screen subjects. Begin running the first experiment on alertness and cognitive performance.

As a basis for accomplishing the first aim, David Sliney, Ph.D. of Aberdeen Proving Ground provided a draft independent safety analysis based on criteria from the American College of Government and Industrial Hygiene (ACGIH) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP) during the first year of the project. The report was finalized during the current year of work. It confirmed that the blue solid-state prototype operates "at all wavelengths and emission levels that are far below limits that are recognized as maximal safe exposure values." Once finalized, the report was distributed to James Maida at JSC and Charles Bowen, Ph.D. of Lockheed Martin for review. In turn, they confirmed that the prototype meets NASA’s standards and applications. No further work is needed on this aim.

Towards the second aim, Apollo Light Systems, Inc. fabricated and delivered a second solid state blue light exposure unit to Jefferson’s Light Research Program. This light source was installed into an exposure system and characterized for spectral output and intensity control. It has been utilized in the melatonin bench-marking studies. No further work is needed on this aim.

For the third aim, human subject recruitment has been completed for the melatonin suppression bench-marking study with blue solid-state light. A total of 84 nighttime experiments with these subjects have been completed. Assay of plasma melatonin samples have been completed and data analysis has begun for this study. Preliminary data assessment indicates that two subjects may have to repeat an exposure night due to technical difficulties. Although a majority of this aim is completed, work will continue into year 3.

The fourth and fifth aims have now been accomplished, and the design is complete for our first study on the effect of blue solid-state light on alertness and cognitive performance in healthy subjects. Jefferson’s IRB formally approved the protocol on 4/17/08. Although protocol amendments may be submitted in the coming year, we are now enabled to start subject recruitment.

We are continuing work on the sixth aim. A sleep medicine physician is consulting with us on implementing polysomnography in this project, and we have hired two part time polysomnography technicians. The first polysomnography training session for the Light Research program staff was conducted on 7/9/08. Determination and purchase of the necessary polysomnography analysis software is underway. Testing of alertness and cognitive performance is being done in a separate phase-shift study, and we are currently determining if these techniques will be suitable in this project on acute alertness.

We will begin work on the seventh aim when we approach completion of the sixth aim. Subject recruitment involves a lengthy interview process, followed by a tour of the live-in laboratory where volunteers will stay for three days. Once volunteers commit to participating, they must avoid prescription or non-prescription drugs, over-the-counter drugs, recreational/street drugs, and other foreign substances. Urine toxicology screens will check compliance for these criteria. Subjects will be required to maintain a scheduled sleep-wake and light-dark cycle prior to the study, complete a daily sleep-wake log and Epsworth Sleepiness Scale, and phone into a voice mailbox to record the bed time and wake up time each day. For at least one week prior to entry into the laboratory study, they will wear a wrist activity monitor to ensure compliance with the screening criteria for maintaining a consistent sleep-wake schedule. In addition, they will be screened medically by a physician and psychologically by a clinical psychologist. Both before and after the study, subjects will have eye screens by a neuro-ophthalmologist. Failure to comply with any of these requirements will result in exclusion from the study. Work on this aim may begin as soon as August of 2008.

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. The impact of these dangers affects many industries, including transportation, manufacturing, communications, and medicine. It has long been a source of concern for the military, as well. Many people also experience the same effects after air travel across several time zones. In the past, the U.S. Air Force has supported our laboratory to study the acute alerting effects of light (French et al., 1990; Brainard et al., 1996). Our current work for NIH has continued this effort (Lockley et al., 2006).

Existing therapeutic interventions using light stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation. A more efficient intervention with increased potency and/or fewer side effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD), also known as winter depression. It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, subsyndromal Seasonal Affective Disorder (sSAD) (Lam and Levitt, 1999). Similar bright white light interventions are also used to treat jetlag. Side effects from exposure to bright white light for these and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity, and potentially fewer side effects. Our group has completed Phase I testing of light therapy with blue solid-state lighting for SAD patients (Glickman et al., 2006).

This year we developed a second blue light exposure system that greatly enhances our ability to run studies more efficiently. Our two solid-state blue light sources are identical in construction, installed into identical exposure stations, and equivalent in performance. Each light source consists of an array of 5,776 blue LEDs (peak 475 nm). These LED prototypes provide a large, uniform light emitting surface with intensity modulation. The donation of the second light source illustrates the continuing commitment of Apollo Light Systems, Inc. to work with our laboratory as an NSBRI Industrial Partner.

The safety evaluation of the prototype blue solid state light sources has been completed. David Sliney, Ph.D., provided an independent safety analysis based on national (ACGIH) and international (ICNIRP) criteria. His final report confirms that the prototype light units operate “at all wavelengths and emission levels that are far below limits that are recognized as maximal safe exposure values.” James Maida at JSC and Charles Bowen, Ph.D., of Lockheed Martin reviewed this report. They confirmed that the units meet NASA’s safety standards and were co-authors with our team on an abstract showing the safety evaluation results at NASA’s 2008 HRP Investigators Workshop.

The aims of the bench-marking melatonin suppression study were to characterize the biological potency of the prototype light units and guide the selection of the light intensity to be tested in the first alertness study. Eight healthy men and women participated in this within-subjects study, completing a total of 84 nighttime melatonin suppression experiments. Assays of plasma melatonin samples have been completed and data analysis has begun. Although further analysis is required, the preliminary data show that the blue LED light evokes a dose-response melatonin suppression in healthy subjects (p<0.001). Although a majority of this aim is completed, work on it will continue into year 3.

This year, our collaborative team completed the design of our first study on the effect of blue solid-state light on alertness and cognitive performance. Jefferson’s IRB has formally approved the protocol. In parallel, we are establishing polysomnography and behavioral testing techniques for this project. The LRP staff had their first polysomnography training session on 7/9/08. Once the polysomnography and behavioral testing techniques are operational, we plan to begin subject recruitment for the first alertness study, possibly before the start of year 3 funding.

This is a new, directed research project. To initiate the work, we proposed the following seven aims:

1) Assemble a team of investigators who will create a set of study designs to be run from 2006 to 2012.

2) Establish either collaborative, consultant or subcontract agreements for elements of the work which are best done outside of Thomas Jefferson University (TJU).

3) Write and secure Institutional Review Board (IRB) approval of the first study design.

4) Design and fabricate the initial solid-state light sources for testing. These sources will serve as the independent variables in the initial study design.

5) Have an independent safety analysis completed on the solid-state lighting prototypes.

6) Purchase and calibrate equipment for assessing alertness and cognitive performance in the study volunteers.

7) Develop a multiyear plan for the development and testing of specific lighting technologies that can be installed in the CEV and other space exploration habitats for acutely enhancing astronaut and ground crew alertness.

Towards accomplishing the first two aims, written correspondence, phone calls and direct meetings were used to establish the team of investigators. Over the first year, a total of eight meetings were held: five meetings at TJU in Philadelphia, one in League City during the NASA Human Research Program Investigators Workshop, one at the External Advisory Committee meeting in Houston, and one at Johnson Space Center (JSC). As a result of these meetings, key collaborators who have formally agreed to participate on this project. These include James Maida of JSC's Habitability and Human Factors Branch; Charles Bowen, Ph.D. of Lockheed Martin's Human Factors Design team; David Dinges, Ph.D. and Namni Goel, Ph.D. from the University of Pennsylvania; Stephen Lockley, Ph.D. of Brigham and Womens Hospital and Harvard Medical School; David Sliney, Ph.D. of the U.S. Army Laser/Optical Radiation Program at Aberdeen Proving Ground; and Mark Rollag, Ph.D. of the University of Virginia. These collaborators will work with scientists and staff of TJU's Light Research Program (LRP) towards accomplishing the goals of this project. The collaborators will work on selected aspects of this project as per their expertise.

Progress towards the third aim involves the development of two experiments. Subject recruitment for the first experiment will be initiated during this month (the end of the first funding year) and the study will be completed in the second funding year. The second experiment will be initiated and run during the second year. The first experiment is a bench-marking study to characterize the biological potency of the prototype solid-state light source that is described below. A within-subjects, acute light-induced melatonin suppression study will be done with eight healthy men and women. This study will have two important outcomes. First, it will help characterize the biological efficacy of the prototype solid-state light source relative to monochromatic and polychromatic light sources previously studied in our lab. In addition, it will guide the selection of the light intensity that will be tested in the second study, which will focus on alertness. The IRB for the first study has been approved by TJU. The protocol for the second experiment, a two-day study on the alerting effects of blue light, is still being refined. Once the experimental design is completed, a separate IRB covering that work will be written and submitted for review.

Progress towards the fourth aim involves our collaboration with Apollo Light Systems, Inc., an industrial partner of NSBRI. Apollo has donated engineering time and materials to develop a large panel of narrowband blue LEDs. This light source will be the independent variable in the first two experiments discussed above. Working closely with an engineer from Apollo, we have modified the original prototype so it can provide a broad range of light intensities with no change to spectral output. Jefferson's LRP staff has thoroughly characterized the prototype radiometry and photometry. This light unit is now completely serviceable for experimental use.

Concerning our fifth aim, David Sliney, Ph.D. of Aberdeen Proving Ground has made a series of radiometric measurements of the prototype and has provided an independent safety analysis based on criteria from the American College of Government and Industrial Hygiene (ACGIH) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). His draft report confirms that the blue solid-state prototype operates "at all wavelengths and emission levels that are far below limits that are recognized as maximal safe exposure values." Once finalized, the report will be distributed to James Maida at JSC and Charles Bowen, Ph.D. of Lockheed Martin for review.

For our sixth aim, we have purchased and received polysomnography and psychomotor vigilance task equipment. Setup, testing, and calibration of this equipment has been initiated and will be completed prior to the start of our second experiment. This equipment will not be needed for the first bench-marking experiment.

Finally, for the seventh aim, extensive discussions have been held between TJU's LRP and the extramural collaborators concerning a multiyear plan for the development and testing of specific lighting technologies that can be installed in the CEV and other space exploration habitats for acutely enhancing astronaut and ground crew alertness. The specific experiments, experiment sequence, and technology development will be determined once data is available from the first two studies.

Aside from evidence of a breakdown in physical health, the effects of circadian disruption and sleep loss have long been known to have potentially dangerous behavioral effects. Mental fatigue, diminished alertness, loss of psychomotor coordination and decreased physical performance are all commonly found in individuals with sleep loss, sleep debt, or circadian misalignment. The impact of these dangers affects many industries, including transportation, manufacturing, communications, and medicine. It has long been a source of concern for the military, as well. Additionally, many people experience the same effects due to air travel across several time zones. The U.S. Air Force has supported our laboratory in the past to study the acute alerting effects of light (French, et al., 1990; Brainard, et al., 1996).

A number of existing therapeutic interventions using light stand to benefit from enhancing our understanding of how different wavelengths of the spectrum affect human circadian and neurobehavioral regulation. A more efficient intervention with increased potency and/or fewer side-effects could result. One such disorder currently being treated with bright white light is Seasonal Affective Disorder (SAD), also known as winter depression. It is estimated that as many as 1 in 5 Americans suffer from SAD or its milder version, subsyndromal Seasonal Affective Disorder (sSAD) (Lam and Levitt, 1999). Similar bright white light interventions are also used for treating jetlag. Side effects from exposure to bright white light for this and other therapies include: hypomania, headache, vision problems, nausea, dizziness, and anxiety. Optimizing the light spectrum for specific affective and/or circadian-related disorders could deliver the same medical impact with lower levels of light intensity, and potentially fewer side-effects. Our group has initiated Phase I testing of light therapy with blue solid-state lighting for SAD patients (Glickman, et al., 2006).

For this project, we are collaborating with Apollo Light Systems, Inc., an NSBRI industrial partner, to develop a large panel of blue LEDs to serve as the independent variable in our first two experiments. Working closely with Apollo, we have modified the original prototype so it can be adjusted to provide a broad range of light intensities with no change in spectral output. Our laboratory has thoroughly characterized the prototype’s radiometry and photometry and it is now ready for use in our first two experiments.

Dr. David Sliney, a key collaborator on this project, has made a series of radiometric measurements of the prototype and has provided an independent safety analysis based on criteria from the American College of Government and Industrial Hygiene (ACGIH) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). His draft report confirms that the blue solid-state prototype operates “at all wavelengths and emission levels that are far below limits that are recognized as maximal safe exposure values.” Once finalized, the report will be distributed to James Maida at JSC and Charles Bowen, Ph.D. of Lockheed Martin for review.

This progress enables the initiation of the first experiment, a bench-marking study to characterize the biological potency of the prototype light. The study employs a within-subjects light-induced melatonin suppression protocol with healthy men and women. The study is approved by Jefferson’s IRB, and subject recruitment has been initiated. This study will be completed during the coming year and will have two important outcomes: it will help characterize the biological efficacy of the prototype light source relative to other light sources previously studied in our lab, and it will guide light intensity selection for the second experiment on the effect of blue light on alertness.

Our laboratory has acquired polysomnography and psychomotor vigilance task equipment for studying the alerting characteristics of this prototype light source. Although not needed for the first bench-marking experiment, setup, testing, and calibration of this equipment has been initiated and will be completed prior to the start of the alertness experiment. During the coming year, the alertness protocol design will be completed and a separate IRB covering that work will be submitted. Once IRB approval is granted, the study will be initiated.

This is a new, directed research project. To initiate the work, we proposed the following seven aims:

1) Assemble a team of investigators who will create a set of study designs to be run from 2006 to 2012.

2) Establish either collaborative, consultant or subcontract agreements for elements of the work which are best done outside of Thomas Jefferson University (TJU).

3) Write and secure Institutional Review Board (IRB) approval of the first study design.

4) Design and fabricate the initial solid-state light sources for testing. These sources will serve as the independent variables in the initial study design.

5) Have an independent safety analysis completed on the solid-state lighting prototypes.

6) Purchase and calibrate equipment for assessing alertness and cognitive performance in the study volunteers.

7) Develop a multiyear plan for the development and testing of specific lighting technologies that can be installed in the CEV and other space exploration habitats for acutely enhancing astronaut and ground crew alertness.

Towards accomplishing the first two aims, written correspondence, phone calls and direct meetings were used to establish the team of investigators. Over the first year, a total of eight meetings were held: five meetings at TJU in Philadelphia, one in League City during the NASA Human Research Program Investigators Workshop, one at the External Advisory Committee meeting in Houston, and one at Johnson Space Center (JSC). As a result of these meetings, key collaborators who have formally agreed to participate on this project. These include James Maida of JSC's Habitability and Human Factors Branch; Charles Bowen, Ph.D. of Lockheed Martin's Human Factors Design team; David Dinges, Ph.D. and Namni Goel, Ph.D. from the University of Pennsylvania; Stephen Lockley, Ph.D. of Brigham and Womens Hospital and Harvard Medical School; David Sliney, Ph.D. of the U.S. Army Laser/Optical Radiation Program at Aberdeen Proving Ground; and Mark Rollag, Ph.D. of the University of Virginia. These collaborators will work with scientists and staff of TJU's Light Research Program (LRP) towards accomplishing the goals of this project. The collaborators will work on selected aspects of this project as per their expertise.

Progress towards the third aim involves the development of two experiments. Subject recruitment for the first experiment will be initiated during this month (the end of the first funding year) and the study will be completed in the second funding year. The second experiment will be initiated and run during the second year. The first experiment is a bench-marking study to characterize the biological potency of the prototype solid-state light source that is described below. A within-subjects, acute light-induced melatonin suppression study will be done with eight healthy men and women. This study will have two important outcomes. First, it will help characterize the biological efficacy of the prototype solid-state light source relative to monochromatic and polychromatic light sources previously studied in our lab. In addition, it will guide the selection of the light intensity that will be tested in the second study, which will focus on alertness. The IRB for the first study has been approved by TJU. The protocol for the second experiment, a two-day study on the alerting effects of blue light, is still being refined. Once the experimental design is completed, a separate IRB covering that work will be written and submitted for review.

Progress towards the fourth aim involves our collaboration with Apollo Light Systems, Inc., an industrial partner of NSBRI. Apollo has donated engineering time and materials to develop a large panel of narrowband blue LEDs. This light source will be the independent variable in the first two experiments discussed above. Working closely with an engineer from Apollo, we have modified the original prototype so it can provide a broad range of light intensities with no change to spectral output. Jefferson's LRP staff has thoroughly characterized the prototype radiometry and photometry. This light unit is now completely serviceable for experimental use.

Concerning our fifth aim, David Sliney, Ph.D. of Aberdeen Proving Ground has made a series of radiometric measurements of the prototype and has provided an independent safety analysis based on criteria from the American College of Government and Industrial Hygiene (ACGIH) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). His draft report confirms that the blue solid-state prototype operates "at all wavelengths and emission levels that are far below limits that are recognized as maximal safe exposure values." Once finalized, the report will be distributed to James Maida at JSC and Charles Bowen, Ph.D. of Lockheed Martin for review.

For our sixth aim, we have purchased and received polysomnography and psychomotor vigilance task equipment. Setup, testing, and calibration of this equipment has been initiated and will be completed prior to the start of our second experiment. This equipment will not be needed for the first bench-marking experiment.

Finally, for the seventh aim, extensive discussions have been held between TJU's LRP and the extramural collaborators concerning a multiyear plan for the development and testing of specific lighting technologies that can be installed in the CEV and other space exploration habitats for acutely enhancing astronaut and ground crew alertness. The specific experiments, experiment sequence, and technology development will be determined once data is available from the first two studies.

Although the studies being considered in this project are focused on developing a non-pharmacological lighting countermeasure for space exploration, it is anticipated that there also will be significant benefits to civilians living on Earth. A significant portion of the global population suffers from chronic sleep loss and/or circadian-related disorders. Evidence for disease or illness occurring due to a disruption of circadian homeostasis has mounted significantly in the past several years. In the United States, 20 million Americans do shift work which interferes with a biologically healthy nocturnal sleep cycle (U.S. Congress OTA, 1991). This group has been shown to be more likely to suffer from a wide variety of ailments, including cardiovascular disease, gastrointestinal distress, cognitive and emotional problems. Furthermore, recent epidemiological studies of female night-shift nurses have shown that they are statistically more likely to suffer from breast cancer and colon cancer compared to day shift workers. Our laboratory is involved in testing the hypothesis that exposure to light at night is a risk factor for cancer (Blask, et al., 2005).