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Life and death in otolaryngology: mechanisms of apoptosis and its role in the pathology and treatment of disease.

OBJECTIVES: To review recent advances in our understanding of programmed cell death, or apoptosis, and discuss implications of these basic science advances in our understanding of causes and potential treatments of a variety of diseases of the head and neck. DATA SOURCES: Basic science literature relevant to the study of apoptosis and its clinical implications. CONCLUSIONS: Apoptosis is now understood to be important in the normal development and survival of all multicellular organisms. Deregulation of this normally tightly controlled process underlies a variety of disease states, including neoplasia, autoimmune disease, and disorders of the central nervous system. A better understanding of this process and its regulation may help otolaryngologists better understand diseases relevant to this specialty and will lead to improved therapeutic interventions.

Apoptosis↗

The impact of an elective curriculum in pathology.

Under the revised medical curriculum at Duke University, elective courses were offered in the third and fourth years beginning in 1968-1969. Departmental electives in autopsy, surgical, and systemic pathology were offered as major courses, and the subspecialty courses in cardiovascular, renal, pulmonary, pediatric, and neuropathology were taught by specialists in those areas. Special topics in subcellular and molecular pathology, neoplasia, environmental diseases, and experimental pathology were subscribed by medical and graduate students alike. To determine the impact of elective courses in pathology, these electives were compared to those offered by other basic science disciplines. Tabulation of total courses offered, student enrollment, and total academic credit hours were constructed for each basic science area. The data show that over the six year study period the students elected more courses in pathology than in any other basic science. The most heavily subscribed electives in pathology were those that were clinically oriented, such as cardiovascular or renal pathology. One impact of this elective system may be to enhance recruitment. During the period studied, 29 Duke graduates interned in pathology compared to six under a comparable time period in the traditional curriculum.

Curriculum↗

The application of basic science concepts to clinical problem-solving.

This study looks at the relationship between anatomical concepts held by medical students and their clinical application, and develops a testable model of how students use basic science concepts for clinical problem-solving. According to the model, the essential prerequisites to solve a clinical problem using basic science information include the appropriate basic science knowledge, the ability to collect and interpret clinical information, with the key concept being the link that must then be made between clinical data and basic science. A detailed analysis of the individual components of the model should help to clarify and resolve some of the debate about the nature and balance of basic science and clinical education. A neurological diagnostic problem was used to test the assumptions of the model in a group of medical students who had minimal clinical experiences. There was no demonstrable relationship between anatomical knowledge as assessed by conventional tests and the diagnosis. There was a powerful relationship between measures of organization of knowledge and diagnosis, suggesting that the organization and development of concepts is the key to correct diagnosis. The findings have significant implications for assessment purposes and suggest that standard methods as generally practised may not measure the appropriate conceptual development and are not congruent with curricular objectives. Through the examination of its different learning outcome measures, the model may also be used to provide a profile of individual students or classes, which should help teachers and students deal with difficulties that may be experienced in learning to link clinical and basic science concepts.

Clinical Competence↗

Biomass Production System (BPS) plant growth unit.

The Biomass Production System (BPS) was developed under the Small Business Innovative Research (SBIR) program to meet science, biotechnology and commercial plant growth needs in the Space Station era. The BPS is equivalent in size to a double middeck locker, but uses its own custom enclosure with a slide out structure to which internal components mount. The BPS contains four internal growth chambers, each with a growing volume of more than 4 liters. Each of the growth chambers has active nutrient delivery, and independent control of temperature, humidity, lighting, and CO2 set-points. Temperature control is achieved using a thermoelectric heat exchanger system. Humidity control is achieved using a heat exchanger with a porous interface which can both humidify and dehumidify. The control software utilizes fuzzy logic for nonlinear, coupled temperature and humidity control. The fluorescent lighting system can be dimmed to provide a range of light levels. CO2 levels are controlled by injecting pure CO2 to the system based on input from an infrared gas analyzer. The unit currently does not scrub CO2, but has been designed to accept scrubber cartridges. In addition to providing environmental control, a number of features are included to facilitate science. The BPS chambers are sealed to allow CO2 and water vapor exchange measurements. The plant chambers can be removed to allow manipulation or sampling of specimens, and each chamber has gas/fluid sample ports. A video camera is provided for each chamber, and frame-grabs and complete environmental data for all science and hardware system sensors are stored on an internal hard drive. Data files can also be transferred to 3.5-inch disks using the front panel disk drive.

Air Conditioning↗

Mechanisms of ventilator-induced lung injury.

OBJECTIVES: To describe the physiologic mechanisms of ventilator-induced lung injury and to define the major ventilator and host-dependent risk factors that contribute to such injury. DATA SOURCE: Basic science and clinical studies related to ventilator-induced barotrauma and lung pathophysiology. STUDY SELECTION: Emphasis on controlled, experimental studies and clinical studies related to specific mechanisms. DATA EXTRACTION: Preference given to studies with quantitative end-points to assess damage and causal relationships. DATA SYNTHESIS: Related studies are integrated to obtain basic mechanisms of damage where possible. CONCLUSIONS: Ventilation with high tidal volumes can increase vascular filtration pressures; produce stress fractures of capillary endothelium, epithelium, and basement membrane; and cause lung rupture. Mechanical damage leads to leakage of fluid, protein, and blood into tissue and air spaces or leakage of air into tissue spaces. This process is followed by an inflammatory response and possibly a reduced defense against infection. Predisposing factors for lung injury are high peak inspiratory volumes and pressures, a high mean airway pressure, structural immaturity of lung and chest wall, surfactant insufficiency or inactivation, and preexisting lung disease. Damage can be minimized by preventing overdistention of functional lung units during therapeutic ventilation.

Barotrauma↗

Comparison of performance of students from different high school systems in medical sciences at Kuwait University.

Data, although limited, question the validity of the formula applied for admission to the medical school in which high school grades are the only preselection variable applied. Comparison between two groups of students from two different high school systems in Kuwait was carried out to determine if the admission criteria used currently for entry to the medical school are equally valid for both groups. The results are based on the students' performances in the first three-semester programme of medical sciences. Subjects covered were anatomy, physiology, biochemistry and behavioural sciences. The group derived from the High School National Diploma performed significantly better with a percentage pass rate of 82% while of those who were derived from the Course Credit System only 61% passed the final examination. In addition, only one of the latter group attained total marks of more than 80% compared to 12 students from the National Diploma group. The percentage failure according to subjects was consistently higher among the Course Credit graduates in all the subjects. All differences between the two groups are statistically significant (P less than 0.001).

Achievement↗

A knowledge-based system to aid with the clinical interpretation of complex serum protein data.

In every area of science workers are finding increasing difficulty in managing the volume of available data. In medicine, the accelerating pace has the worrisome overtones of our failing to provide up-to-date care for our patients. In other information-intensive areas, we rely heavily on software that manages much of the complexity unseen. Patient care could benefit enormously from the incorporation of "knowledge-based" programs to aid with diagnosis and management of many disorders. This article describes such a system designed to organize complex data which can be viewed as a test cluster aimed at many disorders pertinent to serum proteins. This program performs complex tasks such as reference range adjustment, ICD-9 code assignment, and searching for diagnostic "signatures", to generate clinically relevant text and simple graphics. The results have been remarkably accurate and produce repeatable results at the rate of approximately 10 cases per minute. The reluctance to embrace software assistance in laboratory medicine may have serious consequences in the short term and disastrous results within a decade. Expanding the limited algorithm described here to include more traditional chemistry testing could provide the very assistance that all in clinical care desire, a laboratory tool as powerful and adaptable as the traditional physical exam.

Artificial Intelligence↗

Bone mineral density of lumbar vertebral end plates in the aging male sand rat spine.

STUDY DESIGN: Lumbar vertebral segments from young and old male sand rats were assessed for quantitative determination of lumbar end plate bone mineral density. OBJECTIVES: To determine whether bone mineral density increases in the lumbar end plate with age in the male sand rat and to investigate its relationship to disc degeneration. SUMMARY OF THE BACKGROUND DATA: Few basic science studies evaluated the end plate and disc degeneration. The sand rat provides an excellent economical model in which disc degeneration is reliable and well characterized. METHODS: Bone mineral density data on cranial and caudal lumbar end plates of young (mean age 6.8 months) and old (mean age 23.3 months) male sand rats were assessed for changes related to age, lumbar position, and radiologic features. RESULTS: Mean bone mineral density was significantly greater in end plates in older compared to younger males (P <or= 0.0018). Mean end plate bone mineral density within young animals was not significantly different in levels L5 to L7; in old animals, bone mineral density was significantly different (greater) progressing from L5 to L7 (P < 0.0001). In older animals, mean end plate bone mineral density for each disc showed a significant increase with lower lumbar sites (P = 0.0068). Mean end plate bone mineral density was significantly greater in animals with radiographic evidence of disc wedging (P = 0.006). End plate bone mineral density correlated positively with age. CONCLUSIONS: Results provide quantitative bone mineral density data on end plate sclerosis in male sand rats. Data reveal site specificities and show that in old animals, end plate bone mineral density is greater than in young animals. Mean end plate bone mineral density was significantly greater at sites with radiographic disc wedging (P = 0.006). Data support the hypothesis that end plate sclerosis may play a role in disc degeneration.

Aging↗

The new Russian minorities: a statistical overview.

The author "presents a succinct review of the newly constituted Russian minorities situated in the former Soviet republics. Based on census data series (1897 to 1989) and original computations, the paper covers location (highest proportion of Russians in Kazakhstan, Latvia, and Estonia), concentration (predominantly urban), occupational structure (largely in industry and science), and related data on issues such as language affinities and migration."

Communication↗

Gender differences in patenting in the academic life sciences.

We analyzed longitudinal data on academic careers and conducted interviews with faculty members to determine the scope and causes of the gender gap in patenting among life scientists. Our regressions on a random sample of 4227 life scientists over a 30-year period show that women faculty members patent at about 40% of the rate of men. We found that the gender gap has improved over time but remains large.

Authorship↗

Dental characteristics of a large military population useful for identification.

The number and complexity of dental restorations has decreased for younger Americans. Since the presence and extent of restorations are important data for forensic science identification purposes, the Computer-Assisted Postmortem Identification (CAPMI) system was used to assess the practical effect of the decreased selectivity expected as a result of improved dental health. Dental examination data from 7030 soldiers were recorded on optical mark read forms and entered into a database. The data were reorganized and analyzed to generate summary statistics about the incidence of each type of restoration (divided into 16 categories) for both anterior, posterior, upper, lower, and combined segments. Patients' ages ranged from 17 to 49 with a mean of 24 years 5 months. Sixty percent were from 18 to 25 years old. A characteristic is defined as any situation other than a virgin tooth; for example, extracted, missing, unerupted, or restored. The average subject had 7 dental characteristics with approximately 75% having 4 or more. Within the entire population, 9% had 32 unrestored teeth. 3.6% had only one characteristic. To test the selectivity and uniqueness of various combinations of dental characteristics, 363 simulations using the CAPMI system were made against the entire 7030 subject database. Sample records (33 per group) with 2, 3, 4, 5, 6, 7, 8, 9-11, 12-14, 15-18, and 19+ characteristics were chosen at random from the database and searches were made.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

An additional basic science for clinical medicine: I. The constraining fundamental paradigms.

The four main conceptual paradigms of basic biomedical research are that the explication of mechanisms is a primary goal of science; that scientific data must be "hard"; that formulation of hypotheses and counter-hypotheses is a principal creative challenge; and that experiments are the main mechanism for using scientific methods to conduct investigations. Although suitable for the spectacular accomplishments of biomedical research, these paradigms do not offer a satisfactory foundation for the additional basic science needed in the managerial decisions of patient care. For these decisions, the primary scientific goal is usually prediction rather than explication alone; the crucial data often involve "soft" information about clinical and personal phenomena; and the main creative challenge is to develop an improved methodology for getting adequate data and making unbiased comparisons. Although the experiments conducted as randomized clinical trials have been scientifically helpful, the improved methods will have to include evidence obtained in the often unplanned "experiments" of ordinary clinical practice.

Clinical Trials as Topic↗

Event-history analysis for left-truncated data.

"This paper aims at providing a practical guidance for coping with social science event-history data that are left-truncated, especially when the length of exposure prior to observation is known. Only the case of single events is treated, although much of the discussion should be applicable to the case of repeated events, in which only the first spell is likely to be left-truncated. Marital dissolution data from the Panel Study of Income Dynamics (PSID) are used as an example...."

Americas↗

[Multilevel model applications to the analysis of longitudinal data].

This work is an introduction to repeated measurement analysis for longitudinal studies. It uses a two stage modelling framework, using hierarchical linear models with two levels. The first level pertains to the repeated measures, the second level pertains to the individual. For the last 25 years, hierarchical linear models have been used in the Social Sciences to analyse data coming from organizations with multiple levels. Their applications have been extended to the study of change in populations, both to describe the average change in an outcome variable in a population and to analyse the factors associated with variability in the individual trajectories of change. In this article, the basic concepts are introduced: between subjects and within subjects variability, the person-specific model for the individual trajectory and the between person model to describe how individuals vary in their trajectories, fixed and random effects, linear and quadratic growth models. At the end of each section, an illustration is given for the study of cognitive function of the older people cohort "Aging in Leganés", followed in four occasions between 1993 and 1999. Results from fitting the models to answer the most frequently asked research questions in the descriptions and analysis of individual change are presented. Lastly, we present possible generalizations of these linear models to non linear situations which arise when outcomes are dichotomous, nominal or ordinal.

Aging↗

[Proper handling of correlated data in rehabilitation research].

Many study designs in rehabilitation science give rise to correlated data. For example, patients are followed over time, different responses are measured for each patient, or patients are observed in logical units. Standard statistical methods, however, are only valid for independent responses, and careless application of these methods for actually correlated observations might give erroneous results. By means of a simple example, we show how using methods for correlated data can indeed give a gain in statistical power. In the following, different approaches (Summary measures, Repeated Measurement ANOVA, MANOVA, and Mixed Models) to deal with correlated data are presented. We conclude that among these, the Mixed Models approach is the method of choice because it allows flexible modelling of correlation structure and is, meanwhile, also available in standard statistical software packages.

Analysis of Variance↗