Sound localization in the median sagittal plane by listeners with presbyacusis

In Experiment 1, a group of listeners with substantial hearing loss due to presbyacusis and a group of listeners with normal hearing were given three localization tests: a frontal plane test in which they judged whether sounds came from the left, overhead, or the right; a sagittal plane test in which they judged whether sounds came from directly in front, overhead, or behind; and an elevation test in which they judged the vertical position of sounds coming from in front. The two groups performed similarly on the frontal plane test, which chiefly depended upon their ability to use binaural localization cues. They performed differently on the sagittal plane and elevation tests, for which the predominant localization cues were spectral. The listeners with presbyacusis were substantially less accurate than those with normal hearing in both of these instances. They had particular difficulty judging source elevation, rarely scoring much above chance. Follow-up testing of a group of subjects in the early stages of presbyacusis showed localization performance that was intermediate to the other two groups, but far more like that of the normal-hearing listeners. In Experiment 2, additional tests were run with the following conditions designed to encourage improved performance by listeners with presbyacusic hearing loss: (1) filtering of stimuli to preclude masking of more informative high-frequency components by low frequencies; (2) simplification of the elevation test and greater spatial separation of its loudspeaker sources; and (3) use of hearing aids. Conditions 1 and 2 had no appreciable effect on performance; condition 3 significantly improved presbyacusic listeners' ability to localize in the sagittal plane, particularly when sounds came from the front.     

Influence of eccentricity on the frequency limitations of circular-pad via-holes

We study the influence of the technologically caused eccentricity of a circular-pad via-hole. We derive an eigenvalue equation using a rigorous method based on a linear transformation of the via-hole polar coordinates. The eigenvalue equation is used to compute the modal resonant frequencies and the modal fields of the eccentric via. It is shown that the via-hole misalignment shifts the modal frequencies and influences its frequency band. The proposed model is verified with published experimental data, and is also compared with results generated with the full-wave simulator Agilent Momentum-2002.     

Familial hypokalemic periodic paralysis. Clinical, diagnostic and therapeutic aspects

A model of induced lactation was modified to examine the effects of bovine prolactin (bPRL) and bovine placental lactogen (bPL) on mammary growth and differentiation. Thirty-two peripubertal, non-pregnant Holstein heifers were given daily s.c. injections of oestradiol (0.05 mg/kg) and progesterone (0.25 mg/kg) for 7 days to initiate mammary growth. Treatment with bromocriptine (40 mg/3 days) reduced serum PRL concentrations to approximately 25% of pretreatment levels, for the duration of the study. On the day following the last steroid injection, groups of eight heifers were given twice daily s.c. injections of either saline (negative control), recombinant bPRL (rbPRL; 80 mg/day) or recombinant bPL (rbPL; 80 and 160 mg/day) for 7 days. At the end of this period (day 15), growth and differentiation of the mammary glands were assessed. Treatment with rbPL increased total mammary DNA above control value by 50 and 60% for the 80 and 160 mg/day doses respectively. However, total DNA was not different for the control and rbPRL-treated groups. The blood serum concentration of alpha-lactalbumin was measured daily throughout the study and used as an index of mammary differentiation. Both rbPRL and rbPL stimulated mammary differentiation (i.e. induction of milk synthesis), although rbPRL appeared to be more potent than rbPL. These results indicate that rbPL is lactogenic in vivo and strongly suggest that bPL is a mammary mitogen.     

The 9p21 region in bladder cancer cell lines: large homozygous deletion inactivate the CDKN2, CDKN2B and MTAP genes

Homozygous and hemizygous deletions of 9p21 are the earliest and most common genetic alteration in bladder cancer. The identification of two cell cycle regulators, CDKN2 and CDKN2B, that map to the common region of deletion has prompted the hypothesis that they are critical tumor suppressor genes in this malignancy. However, controversy as to whether these genes are the only or even the most important target in bladder cancer oncogenesis remains. To more clearly determine the effect of these 9p21 alterations, we mapped the homozygous deletions and performed a detailed mutational and expression analysis for CDKN2, CDKN2B and a closely linked gene, methylthioadenoside phosphorylase (MTAP), in 16 established bladder cancer cell lines. Nine of the 16 lines exhibit large (30 to > 2000 kb) homozygous deletions on 9p21. All deletions include at least one exon of CDKN2, eight of nine include CDKN2B, and six of nine include MTAP. MTAP function correlates with the genomic deletions. SSCP and sequence analysis does not reveal any inactivating point mutations of CDKN2 or of CDKN2B in any of the cell lines without homozygous deletions, and all express the CDKN2 and the CDKN2B mRNA as well as the encoded p16 protein. The p16 protein levels vary widely and are correlated with absent pRb expression. We conclude that the 9p21 deletions in bladder cancer usually inactivate the CDKN2. CDKN2B, and MTAP genes but that CDKN2 is the most common target. Other mechanisms for inactivating this gene in bladder cancer appear to be uncommon.     

Genetic selection strategies: computer modeling

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.     

Aggressive drug therapy for rheumatoid arthritis

Recent data indicate that rheumatoid arthritis is more often systemic, progressive, and disabling than benign, and that it reduces life expectancy. The new evidence argues for a dramatic alteration in pharmacologic management. If several months of rest, exercise, and anti-inflammatory therapy are ineffectual, aggressive treatment with disease-modifying antirheumatic and immunosuppressive agents may be in order.