The role of nuclear factor NF-Y/CP1 in the transcriptional regulation of the human aldehyde dehydrogenase 2-encoding gene.

Mitochondrial aldehyde dehydrogenase (ALDH2) activity is produced at low levels in many tissues, with highest production in liver. Transfection assays using the first 600 bp of upstream DNA provided evidence for both positive and negative regulatory elements in the proximal promoter. A region from -79 to -116 bp was protected in DNase I footprinting assays and bound in electrophoretic mobility shift assays (EMSA) by a nuclear factor found in all cell lines and tissues tested. This region, denoted FP160, contained the consensus recognition sites for Sp1 and AP2, and a CCAAT box. The CCAAT box was specifically protected by a nuclear factor in methylation interference assays. Mutagenesis of specific bp within the CCAAT box eliminated protein binding in vitro and decreased transcriptional activity from the ALDH2 promoter approximately 50% in reporter gene assays. Competition experiments showed that the nuclear factor binding to the FP160 oligodeoxyribonucleotide (oligo) was competed by oligos corresponding to an NY-Y/CP1-binding site to a greater extent than by those containing sites for CTF/NF1, C/EPB or CP2. The heat stability, resistance to proteinase K digestion, sensitivity to inhibition of DNA binding by o-phenanthroline, and immunological properties of the liver factor binding to FP160 were very similar to the corresponding properties of NF-Y/CP1. Thus, the proximal ALDH2 promoter was bound by NF-Y/CP1 and this transcription factor may be responsible for the basal expression of the gene observed in most tissues. The NFY-CP1 present in rat liver has similar properties to that previously characterized in M12 B-lymphoma cells and LMTK mouse fibroblasts.

Interrater agreement among psychiatrist in psychiatric emergency assessments.

OBJECTIVE: The authors' purpose in this study was to investigate the interrater agreement among psychiatrists in psychiatric emergency service settings. The interrater reliability of many of the key concepts in psychiatric emergency service settings has not been studied. METHOD: Videotapes of 30 psychiatric emergency service patient assessment interviews conducted by psychiatrists were shown to eight experienced psychiatric emergency service psychiatrists. The eight psychiatrists rated each videotape on dimensions such as severity of depression and psychosis and recommended a disposition for each patient. Interrater reliability was then explored. RESULTS: The level of agreement (intraclass correlation coefficient) among the reviewing psychiatrists was higher for psychosis and substance abuse but lower for psychopathology, impulse control problems, danger to self, and disposition. The reviewers' disposition recommendations did not match well with the assessing psychiatrist's actual disposition, but comparisons with actual practice should be considered only suggestive. CONCLUSIONS: Psychiatric emergency service assessments need improvement. This may be accomplished by exploring the underlying structure of psychiatric emergency service concepts, the creation and validation of structured assessment tools, and the creation of practice guidelines.

Increasing the power of clinical trials through judgment analysis.

A method for increasing the statistical power of clinical trials to detect clinically important differences is described. Inconsistency in physicians' overall judgments of treatment effectiveness adds "noise" to a trial that may mask either the superiority or the inferiority of particular treatments. The method described here uses "judgment analysis" to reduce errors in an individual's overall judgments of treatment effectiveness. The method can also be used to reduce error variance due to differences in judgment between physicians and may thus be particularly useful in multicenter trials. The method is illustrated with results from a recent trial.

Physicians' diagnostic judgments and treatment decisions for acute otitis media in children.

Physicians' diagnoses of acute otitis media (AOM) and their treatment choices were investigated using judgment and decision-making analyses. Thirty-two pediatricians in the Albany, New York, area provided probability judgments of the presence of AOM and made treatment decisions for 32 patient vignettes, each described in terms of historical and examination variables. Their probability judgments were well predicted by linear combinations of the patient variables (R2s ranged from 0.76 to 0.97). Information about the observed condition of the eardrum proved to be most critical to the physicians' diagnoses. They demonstrated good levels of agreement on diagnoses. They varied, however, in their tendencies to treat with amoxicillin rather than another antibiotic. Case vagueness was related to the rate of antibiotic treatment. The rate of antibiotic treatment was higher for vague than for non-vague cases when the mean judged probability of AOM was low. In combination, the findings highlight the importance of performing and interpreting ear examinations and the role that consistent training may have in improving management of AOM.

Aging and multiple cue probability learning: the case of inverse relationships.

Multiple Cue Probability Learning (MCPL) is an important cognitive ability for all age groups that, like other cognitive abilities, depends on information processing speed and working memory capacity--skills that have been found to decline with age. The relation between age and ability to learn direct and inverse probabilistic relationships was studied in two MCPL experiments involving subjects in three age groups. In the first experiment, subjects learned two three-cue tasks following the MCPL paradigm. In the first task, all cues had a direct relation (DR) with the criterion. In the second, one cue had an inverse relation (IR) with the criterion. In the DR task, older subjects were able to learn nearly as well as younger subjects. In the IR task, older subjects performed significantly worse than younger subjects due to an inability to use the inverse cue. In a second experiment involving the IR task, task information (TI) was given, that is, the relation between each cue and the criterion was explicitly described. This eliminated the need for subjects to discover the inverse relation on their own, thus reducing the burden on working memory. Provision of TI resulted in improved performance for the 20-30 and 65-75 year old groups, but not in the 76-90 year old group. Significant differences in performance among age groups remained. These results cannot be fully explained by differences in working memory capacity. It is suggested that flexibility of functioning also plays a role.

Military assistance to safety and traffic services in El Paso: a retrospective analysis.

This study was performed to evaluate the performance of military rotary air medical transport in the El Paso, Texas, region with regard to mortality. A retrospective review of transport and inpatient medical records was undertaken. All trauma patients air transported from January 1, 1996, to February 28, 1998, were included. Patients for whom records were unavailable were excluded. Mean time intervals for prehospital and interhospital transport were calculated. Injury severity and survival data were calculated using Revised Trauma Score, Injury Severity Score, and Trauma and Injury Severity Score (TRISS) methodology. Two hundred sixty-seven patients were eligible for analysis (83% of the total). TRISS analysis predicted 241 survivors; the actual number of survivors was 241 (mean = 0.98, z = 0.03) despite the fact that 6 individuals died who were predicted to live and 3 individuals lived who were predicted to die. We conclude that the actual mortality rate of those patients transported by military aeromedical lift equaled that predicted by TRISS methodology.

GENERALITY OF MULTIDIMENSIONAL REPRESENTATIONS.

Since multidimensional scaling is being used for the dimensionalization of an increasingly broad variety of objects, it is important to have techniques for evaluating the resulting dimensions. The term "generality" is used to refer to the degree to which a dimensional representation for a set of objects can be used to account for behavior in a variety of tasks or situations. It is asserted that generality of a multidimensional configuration is its most important property and that the generality of the results of any multidimensional scaling analysis is a matter for empirical verification. A method using a factor analytic procedure in conjunction with multidimensional scaling to investigate generality is suggested and an example of its use is presented.

Building a strategic technology management program.

Strategic technology management decisions are one of the best opportunities for healthcare providers to positively meet clinical needs, patient expectations and competitiveness goals. Technology management must not be treated as an event (annual capital budgeting) but as a well-thought-out, long-range business plan. A strategic technology management team should be formed that includes all the key strategic business areas, plus ad hoc members from the clinical and biomedical engineering areas. Current and future needs should be assessed and the performance of the plan monitored. A plan will help achieve buy-in from clinicians and reduce unwarranted expenditures on technology.

An A/G polymorphism in the promoter of mitochondrial aldehyde dehydrogenase (ALDH2): effects of the sequence variant on transcription factor binding and promoter strength.

INTRODUCTION: The strong protective effect of the ALDH2*2 mutation on risk of alcoholism suggests that other mutations that reduce mitochondrial aldehyde dehydrogenase (ALDH) activity in the liver might also deter drinking. This study describes a polymorphic locus found in the promoter of the ALDH2 gene that affects expression of reporter constructs. METHODS: Polymerase chain reaction (PCR)-based sequencing was used to search for polymorphisms. The ability of the promoter variants to bind transcription factors apolipoprotein A regulatory protein 1 (ARP-1) and chicken ovalbumin upstream promoter-transcription factor (COUP-TF) was tested in gel retardation assays using in vitro synthesized transcription factors. The variant promoters were tested for transcriptional activity using a heterologous promoter system and transient transfection assays. RESULTS: A common polymorphism (A or G) in the human ALDH2 promoter region was found at -361 base pair (bp) from the translation start site. This polymorphism was found at different frequencies in African Americans, Caucasians, and Asians. The polymorphism occurs adjacent to the core binding motif for the transcription factors COUP-TF and ARP-1. Competition and binding affinity determinations did not show differences in the ability of these two sequences to bind the factors. Reporter genes containing these elements upstream of a basal thymidine kinase promoter had similar activity when transfected into a fibroblast (CV-1) cell line. However, the reporter containing the G allele was more active than that containing the A allele in hepatoma (H4IIEC3) cells. CONCLUSIONS: The -361 bp A/G polymorphism is common in all racial groups tested. The G allele was more active than the A allele in a transfection assay. The basis for this difference is not known. If the differences in activity of the promoter constructs were paralleled by differences in ALDH2 enzyme activity in the liver, this polymorphism could affect risk of alcoholism.