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MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring.

Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

Artificial Intelligence↗

Three-dimensional audio versus head-down traffic alert and collision avoidance system displays.

The advantage of a head-up auditory display for situational awareness was evaluated in an experiment designed to measure and compare the acquisition time for capturing visual targets under two conditions: standard head-down Traffic Alert and Collision Avoidance System display and three-dimensional (3-D) audio Traffic Alert and Collision Avoidance System presentation. (The technology used for 3-D audio presentation allows a stereo headphone user to potentially localize a sound at any externalized position in 3-D auditory space). Ten commercial airline crews were tested under full-mission simulation conditions at the NASA-Ames Crew-Vehicle Systems Research Facility Advanced Concepts Flight Simulator. Scenario software generated targets corresponding to aircraft that activated a 3-D aural advisory (the head-up auditory condition) or a standard, visual-audio TCAS advisory (map display with monaural audio alert). Results showed a significant difference in target acquisition time between the two conditions, favoring the 3-D audio Traffic Alert and Collision Avoidance System condition by 500 ms.

Accidents, Aviation↗

Aerospace technology transfer to breast cancer imaging.

In the United States in 1996, an estimated 44,560 women died of breast cancer, and 184,300 new cases were diagnosed. Advances in space technology are now making significant improvements in the imaging technologies used in managing this important foe. The first of these spinoffs, a digital spot mammography system used to perform stereotactic fine-needle breast biopsy, uses a backside-thinned CCD developed originally for the Space Telescope Imaging Spectrometer. This paper describes several successful biomedical applications which have resulted from collaborative technology transfer programs between the National Aeronautics and Space Administration (NASA), the National Cancer Institute (NCI), and the U.S. Dept. of Health and Human Services Office on Women's Health (OWH). These programs have accelerated the introduction of direct digital mammography by two years. In follow-on work, RTI is now assisting the HHS Office on Women's Health to identify additional opportunities for transfer of aerospace, defense, and intelligence technologies to image-guided detection, diagnosis, and treatment of breast cancer. The technology identification and evaluation effort culminated in a May 1997 workshop, and the formative technology development partnerships are discussed.

Astronomical Phenomena↗

Telemedicine at the top of the world: the 1998 and 1999 Everest extreme expeditions.

The National Aeronautics and Space Administration (NASA) initially established a Commercial Space Center (CSC) in the Department of Surgery at Yale University School of Medicine to further develop and evaluate technologies in information systems, telecommunications applied to medicine, and physiologic sensors. The CSC is known as the Medical Informatics and Technology Applications Consortium (MITAC). The overall purpose for this NASA program is to leverage technology, innovation, and resources from industry and academia through collaborative partnerships. The Yale-NASA CSC/MITAC organized the Everest Extreme Expeditions (E3) for the spring Himalayan climbing seasons in the years 1998 and 1999. The primary mission was to deliver advanced medical support with global telemedicine capabilities to one of the world's most remote and hostile settings--Mount Everest. The purpose was both humanitarian (providing medical support) and scientific (conducting medical and technology research). The Yale team provided medical care for the Everest Base Camp community; conducted validation experiments for several types of advanced medical technologies in this remote, hostile environment; and performed real-time monitoring of selected climbers, while also assessing the basic science of altitude physiology. Additionally, the teams conducted outreach medical care to the citizens of Nepal and provided several educational forums for a variety of medical and nonmedical personnel--including school-age children. As part of the project's mission, the E3 medical teams at both Nepal and New Haven were on a 24-hour emergency call system to deliver medical care in the event of a crisis. Unlike most of the teams at Everest, the mission of E3 was not to climb the 29,028-foot mountain the Nepalese call Sagarmatha ("Sky Head"). The mountain served as an extreme testing ground for telemedicine. The lessons learned from this testbed are reviewed here and further clarify the abilities to provide better health care in remote and extreme environments--which for some may even be their home environment during/after a medical illness.

Altitude Sickness↗

CELSS for advanced manned mission.

An overview of the major concepts of Controlled Ecological Life Support System (CELSS) includes an identification of environmental factors, such as gravity levels, light levels, and growth volume, that influence the type of CELSS system that can be developed. Various plant growth systems are described together with their possible space applications. Life support functions performed by plants include food production, atmosphere regeneration, and water purification. Selected relationships between biological and physical-chemical life support techniques are considered as a part of these functions. Consumers in a CELSS may be humans, animals, or microorganisms, but nutritional, water, and atmosphere requirements of humans are emphasized in this report, as they are the primary requirement drivers for a CELSS design. The human role in waste generation is discussed as it affects plant nutrient availability. The role of waste management systems in recovering nutrients for plant growth and requirements for CELSS are defined for air, water, and food. Both physical and a biological nutrient recovery/waste disposal systems are examined. The separate subsystems of a CELSS are identified and discussed. Nutrient recovery, plant irradiation, automation, and facilities equipment and applications are reviewed with special attention to direct solar irradiation using fiber optics. These subsystems, along with other environmental control systems, such as thermal, humidity, and ventilation, are essential to plant growth in the space environment.

Crops, Agricultural↗

Simulated hand-assisted laparoscopic surgery (HALS) in microgravity.

INTRODUCTION: Previous simulation and porcine experiments aboard the reduced gravity program KC-135 turbojet have demonstrated that microgravity surgery is feasible. Ideally, surgical care in spaceflight will incorporate recent advances in care while remaining easy enough for a crew medical officer (CMO) lacking surgical proficiency or extensive surgical experience to perform. As a minimally invasive surgical technique, hand-assisted laparoscopic surgery (HALS) benefits the patient via smaller incisions, less pain, and faster recovery than traditional open surgery. HALS also helps less experienced laparoscopic surgeons perform laparoscopic surgery. METHODS: An inexpensive inanimate surgical simulator was constructed to evaluate the usefulness of HALS in microgravity. This simulator was utilized during brief periods of microgravity provided by parabolic flight on the KC-135. The simulator was successfully used by both a physician-astronaut and an experienced laparoscopic surgeon. Task completion included simulated surgery with exploration of the intestines and ligation of the appendix. RESULTS: Simulated HALS was successfully performed in microgravity. HALS effectively contained operative equipment and small amounts of introduced fluids within the simulated abdominal cavity. Astronaut and surgeon experience suggest that HALS could facilitate minimally invasive surgery (MIS) in microgravity. DISCUSSION: HALS holds promise as a surgical approach in microgravity, particularly as space travel extends beyond low earth orbit. HALS provides the benefits of MIS, facilitates MIS surgery by less surgically proficient or experienced CMOs, and contains equipment and fluid within the operative field. Simulation provides an easy, cost-effective platform to evaluate medical technology for space flight as well as a method to train CMOs on-orbit.

Appendix↗

Growing crops for space explorers on the moon, Mars, or in space.

An option in the long-duration exploration of space, whether on the Moon or Mars or in a spacecraft on its way to Mars or the asteroids, is to utilize a bioregenerative life-support system in addition to the physicochemical systems that will always be necessary. Green plants can use the energy of light to remove carbon dioxide from the atmosphere and add oxygen to it while at the same time synthesizing food for the space travelers. The water that crop plants transpire can be condensed in pure form, contributing to the water purification system. An added bonus is that green plants provide a familiar environment for humans far from their home planet. The down side is that such a bioregenerative life-support system--called a controlled environment life-support system (CELSS) in this paper--must be highly complex and relatively massive to maintain a proper composition of the atmosphere while also providing food. Thus, launch costs will be high. Except for resupply and removal of nonrecycleable substances, such a system is nearly closed with respect to matter but open with respect to energy. Although a CELSS facility is small compared to the Earth's biosphere, it must be large enough to feed humans and provide a suitable atmosphere for them. A functioning CELSS can only be created with the help of today's advanced technology, especially computerized controls. Needed are energy for light, possibly from a nuclear power plant, and equipment to provide a suitable environment for plant growth, including a way to supply plants with the necessary mineral nutrients. All this constitutes the biomass production unit. There must also be food preparation facilities and a means to recycle or dispose of waste materials and there must be control equipment to keep the facility running. Humans are part of the system as well as plants and possibly animals. Human brain power will often be needed to keep the system functional in spite of the best computer-driven controls. The particulars of a CELSS facility depend strongly on where it is to be located. The presence of gravity on the Moon and Mars simplifies the design for a facility on those bodies, but a spacecraft in microgravity is a much more challenging environment. One problem is that plants, which are very sensitive to gravity, might not grow and produce food in the virtual absence of gravity. However, the experience with growing super-dwarf wheat in the Russian space station Mir, while not entirely successful because of the sterile wheat heads, was highly encouraging. The plants grew well for 123 days, producing more biomass than had been produced in space before. This was due to the high photon flux available to the plants and the careful control of substrate moisture. The sterile heads were probably due to the failure to remove the gaseous plant hormone, ethylene, from the Mir atmosphere. Since ethylene can easily be removed, it should be possible to grow wheat and other crops in microgravity with the production of viable seeds. On the ground Biosphere-2 taught us several lessons about the design and construction of a CELSS facility, but Bios-3 came much closer to achieving the goals of such a facility. Although stability was never completely reached, Bios-3 was much more stable than Biosphere-2 apparently because every effort was made to keep the system simple and to use the best technology available to maintain control. Wastes were not recycled in Bios-3 except for urine, and inedible plant materials were incinerated to restore CO2 to the atmosphere. Since much meat (about 20% of calories) was imported, closure in the Bios-3 experiments was well below 100%. But then, a practical CELSS on the Moon might also depend on regular resupply from Earth. Several important lessons have been learned from the CELSS research described in this review.

Agriculture↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗