Listeners with congenital amusia are sensitive to context uncertainty in melodic sequences.

In typical listeners, the perceptual salience of a surprising auditory event depends on the uncertainty of its context. For example, in melodies, pitch deviants are more easily detected and generate larger neural responses when the context is highly predictable than when it is less so. However, it is not known whether amusic listeners with abnormal pitch processing are sensitive to the degree of uncertainty of pitch sequences and, if so, whether they are to a different extent than typical non-musician listeners. To answer this question, we manipulated the uncertainty of short melodies while participants with and without congenital amusia underwent EEG recordings in a passive listening task. Uncertainty was manipulated by presenting melodies with different levels of complexity and familiarity, under the assumption that simpler and more familiar patterns would enhance pitch predictability. We recorded mismatch negativity (MMN) responses to pitch, intensity, timbre, location, and rhythm deviants as a measure of auditory surprise. In both participant groups, we observed reduced MMN amplitudes and longer peak latencies for all sound features with increasing levels of complexity, and putative familiarity effects only for intensity deviants. No significant group-by-complexity or group-by-familiarity interactions were detected. However, in contrast to previous studies, pitch MMN responses in amusics were disrupted in high complexity and unfamiliar melodies. The present results thus indicate that amusics are sensitive to the uncertainty of melodic sequences and that preattentive auditory change detection is greatly spared in this population across sound features and levels of predictability. However, our findings also hint at pitch-specific impairments in this population when uncertainty is high, thus suggesting that pitch processing under high uncertainty conditions requires an intact frontotemporal loop.

Decomposing neural responses to melodic surprise in musicians and non-musicians: Evidence for a hierarchy of predictions in the auditory system.

Neural responses to auditory surprise are typically studied with highly unexpected, disruptive sounds. Consequently, little is known about auditory prediction in everyday contexts that are characterized by fine-grained, non-disruptive fluctuations of auditory surprise. To address this issue, we used IDyOM, a computational model of auditory expectation, to obtain continuous surprise estimates for a set of newly composed melodies. Our main goal was to assess whether the neural correlates of non-disruptive surprising sounds in a musical context are affected by musical expertise. Using magnetoencephalography (MEG), auditory responses were recorded from musicians and non-musicians while they listened to the melodies. Consistent with a previous study, the amplitude of the N1m component increased with higher levels of computationally estimated surprise. This effect, however, was not different between the two groups. Further analyses offered an explanation for this finding: Pitch interval size itself, rather than probabilistic prediction, was responsible for the modulation of the N1m, thus pointing to low-level sensory adaptation as the underlying mechanism. In turn, the formation of auditory regularities and proper probabilistic prediction were reflected in later components: The mismatch negativity (MMNm) and the P3am, respectively. Overall, our findings reveal a hierarchy of expectations in the auditory system and highlight the need to properly account for sensory adaptation in research addressing statistical learning.

Los límites conceptuales de la esquizofrenia / No disponible

El concepto de esquizofrenia ha sufrido variaciones alo largo de la historia y, actualmente, se discute la necesidadde su propia existencia. A pesar del desarrollo delos sistemas diagnósticos operacionales y del aumentode la confiabilidad interjuicios en el diagnóstico psiquiátrico,la validez de la esquizofrenia continúa siendocuestionada. Las propuestas de reemplazar la esquizofreniay otras psicosis por un síndrome psicótico generalo por nosologías no categoriales (dimensiones) están ala vanguardia de las discusiones vinculadas a la edicióndel DSM-V. En el presente trabajo, se revisa el problemanosológico de la esquizofrenia y sus consecuenciasy se aportan propuestas alternativas para mejorar lavalidez del trastorno(AU)

The concept of schizophrenia had variations alonghistory and the existence of the illness is currently indoubt. Although operational diagnostic systemsimproved interrater reliability, schizophrenia validity isquestioned. In this paper the proposal to change schizophreniaand other disorders for a general psychotic syndromeor a dimensional nosology in DSM-V is discussedand put forward other ideas to improvedisorder’s validity(AU)

Determinants of blood lead levels across the menopausal transition.

In this study, the authors sought to evaluate the impact of menopause on lead remobilization from bone-lead stores. The study was conducted between 1993 and 1995 in Mexico City and included 903 women (mean age = 46.8 y [standard deviation = 8.2 y]). Participants provided information about reproductive variables and known risk factors for high PbB levels. PbB levels were determined with graphite furnace atomic absorption spectrophotometry. The authors used linear-regression models to describe the relationship between PbB levels and variables of interest. PbB levels ranged from 1.0 microg/dl to 43.8 microg/dl (mean = 11.0 microg/dl). Menopausal women at baseline had the highest PbB levels; the mean difference between pre- and postmenopausal women was 0.76 microg/dl (95% confidence interval = 0.024, 1.48). We observed an inverted U-shaped relationship between PbB level and age. The highest PbB levels were observed in women aged 47-50 y. Other important predictors of PbB levels were use of lead-glazed ceramics, number of pregnancies, history of cigarette smoking, and height. Our results support the hypothesis that bone lead may be mobilized during menopause and may constitute an important source of exposure.

Molecular correlations in phenylketonuria: mutation patterns and corresponding biochemical and clinical phenotypes in a heterogeneous California population.

We studied 133 California phenylketonuria (PKU) patients and one obligate heterozygote to delineate the molecular basis of PKU in a population with greater ethnic diversity than in previous studies, and to determine whether a correlation exists between genotype and clinical phenotype, with the latter defined by both the diagnostic pretreatment blood phenylalanine (PHE) level and cognitive (IQ) test scores. To determine PAH genotypes, we used PCR-mediated amplification, denaturing gradient gel electrophoresis, and direct sequencing on dried whole blood samples. Where possible, mutation severity was defined according to predicted in vitro PAH enzyme activity estimated by using Cos cell expression analysis for a given mutation. We then asked whether mutation severity, as defined by such expression analysis, correlated with pretreatment PHE levels or with IQ test results. A mutation was identified in 236 (88%) of 267 mutant alleles. Seventeen new mutant alleles were found; A47E, T81P, I102T, E182G, T328D, Y343P, K371R, Y387H, A389E, E422K, IVS9nt5, IVS11nt20, delS70, del364-368/del198-220, delF299, delT323, and -1C/T. In striking contrast to a number of studies in other populations, in this study, based on predicted PAH activity, we observed no correlation between mutation severity and pretreatment PHE levels. There was also no correlation between genotype and IQ. We conclude that in samples collected from an ethnically heterogeneous population, there is no correlation of mutation severity with either pretreatment PHE levels or IQ measurement in treated patients. We caution that genetic counseling in PKU should incorporate the notion that prognosis may not be predicted with precision based on mutation analysis in a given patient.

Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous southeastern US population.

OBJECTIVE: To determine the molecular basis of phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) and to establish correlations between phenylalanine hydroxylase (PAH) genotypes and biochemical and clinical phenotypes in an ethnically diverse US population, PAH genotypes were determined in 35 patients with PKU or HPA and 1 carrier from the Medical Genetics Clinic of the Emory University School of Medicine. METHODOLOGY: Patients were identified through Georgia's population-based newborn screening program. PAH genotypes in these individuals were determined from dried blood spots or whole-blood samples using a combination of polymerase chain reaction-mediated amplification, denaturing gradient gel electrophoresis, and direct-sequence analysis. The phenotypic severity of patients with PKU and HPA was based on pretreatment serum phenylalanine (PHE) levels during the neonatal period and on dietary tolerance of PHE later in life. RESULTS: Sixty-eight (96%) of 71 mutant alleles were identified. Major mutations in this population included R408W (11 of 71), I65T (11 of 71), Y414C (6 of 71), L348V (4 of 71), and IVS10 (4 of 71). Five new nucleotide substitutions, E76A (1 of 71), R241L (1 of 71), Q304R (2 of 71), C334S (1 of 71), and R400R (2 of 71) were also detected. Thirty-two of the thirty-five nonrelated patients examined in this study were completely genotyped. Strong correlations were observed between the level of PAH activity predicted from the genotype, when known from previous in vitro expression studies of the mutant proteins, and pretreatment serum PHE levels (r = .841) or clinical severity (Kendall rank-order correlation coefficient, .936). CONCLUSIONS: These results demonstrate strong correlations between PAH genotype and biochemical and clinical phenotypes in this heterogeneous American sample population, extending our previous findings from relatively homogeneous European populations. These correlations further demonstrate the clinical utility of genotype analysis in the treatment of patients with PKU and HPA.

[Classification in actual psychiatry]. / Las clasificaciones en la psiquiatría actual.

The importance of diagnosis in psychiatry is relevant for therapeutic, research and public health questions. During the '70s, operational criteria improved ways for developing reliability and the basis of validity of psychiatric diagnosis. However, the possibility of a common language in psychiatry has been in doubt because of the proliferation of operational systems. There are also reductionist trends that could be dangerous for psychopathology and pedagogy.

Las clasificaciones en la psiquiatría actual. / [Classification in actual psychiatry]

The importance of diagnosis in psychiatry is relevant for therapeutic, research and public health questions. During the 70s, operational criteria improved ways for developing reliability and the basis of validity of psychiatric diagnosis. However, the possibility of a common language in psychiatry has been in doubt because of the proliferation of operational systems. There are also reductionist trends that could be dangerous for psychopathology and pedagogy.

Stability of gentamicin sulfate and tobramycin sulfate in extemporaneously prepared ophthalmic solutions at 8 degrees C.

The stability of gentamicin sulfate and tobramycin sulfate in fortified ophthalmic solutions stored under refrigeration was studied. Fortified gentamicin ophthalmic solution and fortified tobramycin ophthalmic solution were prepared to a final theoretical concentration of 13.6 mg/mL by using commercially available ophthalmic and injectable solutions. Volumes of each solution were packaged in plastic bottles and refrigerated at 4-8 degrees C. Samples of each solution were analyzed by fluorescence polarization immunoassay on days 0 (before refrigeration), 1, 2, 3, 4, 7, 14, 28, 63, and 91. To validate the method, identical solutions were prepared, stored under refrigeration at 4-8 degrees C, and analyzed by a stability-indicating high-performance liquid chromatographic assay on days 0 (before refrigeration), 9, 28, 56, and 91. Fluorescence polarization immunoassay showed the mean concentrations of gentamicin and tobramycin on day 91 to be 104.4% and 97.4%, respectively, of the time 0 concentrations; the difference was not significant in either case. HPLC validated these results; the mean concentration of gentamicin and tobramycin on day 91 was 103.3% and 101.2%, respectively, of the mean day 0 concentrations. Gentamicin and tobramycin in ophthalmic solutions prepared by mixing ophthalmic and injectable products and stored in plastic bottles at 4-8 degrees C were stable for three months.

Single-pass imaging through a thick dynamic distorter using four-wave mixing.

We have reconstructed images after a single pass through a thick, turbulent aberrator. The reconstructed image's resolution was independent of the presence, severity, and length of a hot-air aberrator (at least 50 times the collecting optics' depth of field). The slowly responding four-wave mixing medium, fluorescein-doped boric acid glass, averaged out rapidly varying intensity apodizations, which would otherwise degrade the reconstructed image quality.

Effects of thick aberrators in one-way imaging schemes.

The ability of one-way imaging schemes to correct for the effects of thick aberrators is examined. These schemes correct an image for the influence of an intervening aberrator in a single pass. Single-pass image correction is observed for thick aberrators that change in times that are short compared with the nonlinear response time of the four-wave mixing material. Image degradation is observed for static aberrators.

Isolation and Characterization of Coproporphyrin Produced by Four Subspecies of Bacillus thuringiensis.

It was found by using spectrophotometric, spectrofluorometric, and high-pressure liquid chromatography that four subspecies of Bacillus thuringiensis produce coproporphyrin. The porphyrin isomer was identified as coproporphyrin I for B. thuringiensis subsp. kurstaki (HD1). The porphyrin was isolated both from spores and from a variety of spent growth media. The quantity of porphyrin released by each Bacillus subspecies differed. The rank order of porphyrin production follows: B. thuringiensis subsp. kurstaki HD1 > B. thuringiensis subsp. thuringiensis HD27 > B. thuringiensis subsp. thuringiensis HD41 > B. thuringiensis subsp. darmstadiensis HD199.

Adult age differences in memory for motor versus cognitive activities.

Young and elderly participants performed on a series of 12 sustained activities (3 minutes each) under either incidental or intentional memory conditions regarding subsequent recall of those activities. Half of the activities were primarily motor in nature, half primarily cognitive. A significant overall age deficit was found for recall. Most important, in contrast to the contextual support hypothesis, the age deficit was as pronounced for motor activities as for cognitive activities. For both kinds of activities, incidental memory was as proficient as intentional memory.

Drug utilization review of parenteral clindamycin therapy.

A concurrent drug utilization review was conducted to evaluate the appropriateness of parenteral clindamycin use, the incidence of gastrointestinal side effects, and to implement, if necessary, corrective actions to improve parenteral clindamycin use. Criteria for the appropriate use of clindamycin were prepared, reviewed, and approved by the P & T Committee of the City of Memphis Hospital (CMH) and University of Tennessee Medical Center/William F. Bowld Hospital (UTMCH). Forty-five patients were included in the audit. Overall, in 43/45 (96%) of the patients audited, clindamycin use was deemed appropriate. This audit provided the opportunity for positive reinforcement of physician prescribing practices and helped to foster a cooperative, rather than an adversarial relationship, between pharmacists and physicians involved in drug utilization review.

Evaluation of compounding accuracy and aseptic techniques for intravenous admixtures.

Intravenous admixtures containing potassium collected from three hospital pharmacies were analyzed for compounding accuracy, sterility and pyrogenicity. The study was performed in two stages. During stage I, pharmacists and technicians were not informed of the study, but during stage II they were informed. In each stage 10 samples were collected from each person in the two personnel groups, analyzed and the results compared between the two personnel groups and the two stages. Results of the study showed that without monitoring (stage I) pharmacists had a higher mean percent error and contamination level than technicians. With monitoring, however, pharmacists showed a lower mean percent error and contamination level than technicians. Both personnel groups showed a decline in their mean percent error in the second stage, but there were still 83 (39.5%) errors in compounding accuracy greater than +/- 6%. No positive results with the Limulus test for pyrogens were obtained. It is recommended that a planned program of quality control be instituted for the preparation of i.v. admixtures by both pharmacists and technicians.