Development of a clinical and echocardiographic score for assigning risk of major events after exercise and dobutamine echocardiograms

The prognostic value of exercise (EXE) and dobutamine echocardiograms (DbE) has been well defined in large studies. However, while risk is determined by both clinical and echo features, no simple means of combining these data has been defined. We sought to combine these data into risk scores. Methods. At 3 expert centers, 7650 pts underwent standard EXE (n=5211) and DbE (w2439) for evaluation of known or suspected CAD and were followed for up to 10 years (mean 5-2) for major events (death or myocardial infarction). A subgroup of 2953 EXE and 1025 DbE pts was randomly selected to develop separate multivariate models for prediction of events. After simplication of each model for clinical use, models were validated in the remaining EXE and DbE pts. ResuI1s. The total number of events was 200 in the EXE and 225 in the DbE pts, of which 58 and 99 events occurred in the respective testing groups. The following regression equations gave equivalent results I” the testing and validation groups for both EXE and DbE; DbE = (Age’O.02) + (DM’l .O) + (Low RPP’0.6) + ([CHF+lschemia+Scar]‘O.7) EXE = ([DM+CHF]‘O.S) + O.S(lschemla #) + l.B(Scar#) - (METS0.19) (where each categorical variable scored 1 when present and 0 when absent, Ischemia# = 1 for l-2 VD. 6 for 3 VD; Scar# = 1 for 1-2 VD, 1.7 for 3 VD). The table summarizes the scores and equivalent outcomes for EXE and DbE. Conclusions. Risk scores based on clinical and EXE or DbE results may be used to quantify the risk of events during follow-up.

Benefits of amplification for speech recognition in background noise

The purpose of the present study was to examine the benefits of providing audible speech to listeners with sensorineural hearing loss when the speech is presented in a background noise. Previous studies have shown that when listeners have a severe hearing loss in the higher frequencies, providing audible speech (in a quiet background) to these higher frequencies usually results in no improvement in speech recognition. In the present experiments, speech was presented in a background of multitalker babble to listeners with various severities of hearing loss. The signal was low-pass filtered at numerous cutoff frequencies and speech recognition was measured as additional high-frequency speech information was provided to the hearing-impaired listeners. It was found in all cases, regardless of hearing loss or frequency range, that providing audible speech resulted in an increase in recognition score. The change in recognition as the cutoff frequency was increased, along with the amount of audible speech information in each condition (articulation index), was used to calculate the "efficiency" of providing audible speech. Efficiencies were positive for all degrees of hearing loss. However, the gains in recognition were small, and the maximum score obtained by an listener was low, due to the noise background. An analysis of error patterns showed that due to the limited speech audibility in a noise background, even severely impaired listeners used additional speech audibility in the high frequencies to improve their perception of the "easier" features of speech including voicing

Changes in estimated coronary risk in the 1980s: data from 38 populations in the WHO MONICA Project

The World Health Organization (WHO) MONICA Project is a 10-year study monitoring trends and determinants of cardiovascular disease in geographically defined populations. Data were collected from over 100 000 randomly selected participants in two risk factor surveys conducted approximately 5 years apart in 38 populations using standardized protocols. The net effects of changes in the risk factor levels were estimated using risk scores derived from longitudinal studies in the Nordic countries. The prevalence of cigarette smoking decreased among men in most populations, but the trends for women varied. The prevalence of hypertension declined in two-thirds of the populations. Changes in the prevalence of raised total cholesterol were small but highly correlated between the genders (r = 0.8). The prevalence of obesity increased in three-quarters of the populations for men and in more than half of the populations for women. In almost half of the populations there were statistically significant declines in the estimated coronary risk for both men and women, although for Beijing the risk score increased significantly for both genders. The net effect of the changes in the risk factor levels in the 1980s in most of the study populations of the WHO MONICA Project is that the rates of coronary disease are predicted to decline in the 1990s.

Further evidence for a deficit in switching attention in schizophrenia

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B - A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia.

Familial hyperaldosteronism type II: Description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had neg ative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.

Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.

A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: The University of Saskatchewan bone mineral accrual study

To investigate the influence of physical activity on bone mineral accrual during the adolescent years, we analyzed 6 years of data from 53 girls and 60 boys. Physical activity, dietary intakes, and anthropometry were measured every 6 months and dual-energy X-ray absorptiometry scans of the total body (TB), lumbar spine (LS), and proximal femur (Hologic 2000, array mode) were collected annually. Distance and velocity curves for height and bone mineral content (BMC) were fitted for each child at several skeletal sites using a cubic spline procedure, from which ages at peak height velocity (PHV) and peak BMC velocity (PBMCV) were identified. A mean age- and gender-specific standardized activity (Z) score was calculated for each subject based on multiple yearly activity assessments collected up until age of PHV. This score was used to identify active (top quartile), average (middle 2 quartiles), or inactive (bottom quartile) groups. Two-way analysis of covariance, with height and weight at PHV controlled for, demonstrated significant physical activity and gender main effects (but no interaction) for PBMCV, for BMC accrued for 2 years around peak velocity, and for BMC at 1 year post-PBMCV for the TB and femoral neck and for physical activity but not gender at the LS (all p < 0.05). Controlling for maturational and size differences between groups, we noted a 9% and 17% greater TB BMC for active boys and girls, respectively, over their inactive peers 1 year after the age of PBMCV. We also estimated that, on average, 26% of adult TB bone mineral was accrued during the 2 years around PBMCV.

Protein sequence threading, the alignment problem, and a two-step strategy

Conventionally, protein structure prediction via threading relies on some nonoptimal method to align a protein sequence to each member of a library of known structures. We show how a score function (force field) can be modified so as to allow the direct application of a dynamic programming algorithm to the problem. This involves an approximation whose damage can be minimized by an optimization process during score function parameter determination. The method is compared to sequence to structure alignments using a more conventional pair-wise score function and the frozen approximation. The new method produces results comparable to the frozen approximation, but is faster and has fewer adjustable parameters. It is also free of memory of the template's original amino acid sequence, and does not suffer from a problem of nonconvergence, which can be shown to occur with the frozen approximation. Alignments generated by the simplified score function can then be ranked using a second score function with the approximations removed. (C) 1999 John Wiley & Sons, Inc.