Variable but not random: temporal pattern coding in a songbird brain area necessary for song modification.

Practice of a complex motor gesture involves motor exploration to attain a better match to target, but little is known about the neural code for such exploration. We examine spiking in a premotor area of the songbird brain critical for song modification and quantify correlations between spiking and time in the motor sequence. While isolated spikes code for time in song during performance of song to a female bird, extended strings of spiking and silence, particularly bursts, code for time in song during undirected (solo) singing, or "practice." Bursts code for particular times in song with more information than individual spikes, and this spike-spike synergy is significantly higher during undirected singing. The observed pattern information cannot be accounted for by a Poisson model with a matched time-varying rate, indicating that the precise timing of spikes in both bursts in undirected singing and isolated spikes in directed singing code for song with a temporal code. Temporal coding during practice supports the hypothesis that lateral magnocellular nucleus of the anterior nidopallium neurons actively guide song modification at local instances in time.NEW & NOTEWORTHY This paper shows that bursts of spikes in the songbird brain during practice carry information about the output motor pattern. The brain's code for song changes with social context, in performance versus practice. Synergistic combinations of spiking and silence code for time in the bird's song. This is one of the first uses of information theory to quantify neural information about a motor output. This activity may guide changes to the song.

Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

Copper porphyrins in deep-sea sediments: a possible indicator of oxidized terrestrial organic matter.

Copper porphyrins have been isolated from deep-sea sediments collected during six legs of the Deep Sea Drilling Project-International Program of Ocean Drilling. These pigments are present in depositional areas receiving high inputs of terrestrially derived oxidized organic matter. Such areas include the Black Sea, the Bay of Biscay, the Blake-Bahama Basin, and slumped Miocene deposits off Cape Bojador on the west coast of Africa.

Can quantitative computed tomography detect bone morphological changes associated with catastrophic proximal sesamoid bone fracture in Thoroughbred racehorses?

BACKGROUND: Fracture of the proximal sesamoid bones continues to be the most common fatal musculoskeletal injury in US racehorses. Identifying factors that influence fracture risk could lead to screening techniques to reduce catastrophic injury rates and improve animal welfare. OBJECTIVES: To identify morphological differences between proximal sesamoid bones of the contralateral limb of fracture and control horses and assess the feasibility of computed tomography (CT) to detect traits associated with proximal sesamoid bone fracture. We hypothesised that horses with proximal sesamoid bone fracture would have greater bone density. STUDY DESIGN: Cross-sectional cadaver morphological study. METHODS: Proximal sesamoid bone morphology was measured using high-resolution micro-CT images from 16 Thoroughbred racehorses (eight fracture, eight control) euthanised on New York racetracks. Nominal logistic regression models and receiver operating characteristic curves were created to assess the ability of CT-derived morphological traits to accurately classify fracture horses vs. controls. RESULTS: Bone volume fraction was greater in the fracture group (90.39 ± 1.76%) as compared to controls (87.20 ± 2.79%, P<0.0001). Bone volume fraction, bone width, trabecular thickness and degree of anisotropy were significantly different between fracture and control horses. Receiver operating characteristic curves showed that a combined model that incorporates bone volume fraction and width can identify fracture from control horses with an area under the curve of 0.938, indicating high accuracy at classifying fracture horses from controls. MAIN LIMITATIONS: The number of horses per group is small, although the total number of sesamoids imaged is reasonable (n = 62). In vivo CT at the resolution performed in this study is currently unattainable; however, density and width could be measured with quantitative CT. CONCLUSIONS: Differences in proximal sesamoid bone morphology were identified between fracture and control horses. As improved technology becomes accessible, quantitative CT could potentially be used as a clinical imaging technique to estimate proximal sesamoid bone fracture risk in Thoroughbred racehorses.

Restoration of urban waterways and vacant areas: the first steps toward sustainability.

Increased population pressure and human activities have significantly altered the effectiveness of functions of ecosystems ("ecosystem services") at the local and regional scale. Of primary importance is the decrease in water quality due to urban storm water runoff. A number of communities have initiated restoration strategies to improve water quality standards. One such strategy is the incorporation of riparian walkways with native flora. As a result of such restoration efforts, habitats for native fauna have improved, and the number and diversity of wildlife have increased in urban settings. Restoration of urban habitats also provides social and economic benefits to the surrounding community. Efforts to mitigate the loss of ecological resources by restoring native habitats on lots that cannot be developed or on abandoned lots hold a high, unrealized potential. Habitat restoration not only provides natural diversions to urban surroundings, but also enlightens and educates individual citizens about the importance of balanced ecosystems and the role of humans within ecosystems. Education is the primary step toward creating ecologically sustainable communities.

Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis.

Cyclic hematopoiesis, (CH, or cyclic neutropenia) is a rare disease manifested by transient severe neutropenia that recurs approximately every 21 days. The hematologic profile of families with the autosomal dominant form (ADCH) has not been well characterized, and it is unknown if the phenotype is distinct from the more common sporadic congenital or acquired forms of CH. We studied nine ADCH families whose children displayed typical CH blood patterns. Pedigrees confirmed dominant inheritance without evidence of heterogeneity or decreased penetrance; three pedigrees suggested new mutations. Families were Caucasian with exception of one with a Cherokee Native American founder: A wide spectrum of symptom severity, ranging from asymptomatic to life-threatening illness, was observed within families. The phenotype changed with age. Children displayed typical neutrophil cycles with symptoms of mucosal ulceration, lymphadenopathy, and infections. Adults often had fewer and milder chronic neutropenia without distinct cycles. While CH is commonly described as "benign", four children in three of the nine families died of Clostridium or E. coli colitis, documenting the need for urgent evaluation of abdominal pain. Misdiagnosis with other neutropenias was common but can be avoided by serial blood counts in index cases. Genetic counseling requires specific histories and complete blood counts in relatives at risk to assess status regardless of symptoms, especially to determine individuals with new mutations. We propose diagnostic criteria for ADCH in affected children and adults. Recombinant human granulocyte colony-stimulating factor treatment resulted in dramatic improvement of neutropenia and morbidity. The differential diagnosis from other forms of familial neutropenia is reviewed.

Normal mode oscillation in the presence of inhomogeneous broadening.

We investigate effects of inhomogeneous broadening of excitons on normal mode oscillation in semiconductor microcavities using a coupled oscillator model. We show that inhomogeneous broadening can drastically alter the coherent oscillatory energy exchange process even in regimes where normal mode splitting remains nearly unchanged. The depth, frequency, and phase of normal mode oscillations of excitons at a given energy within the inhomogeneous distribution depend strongly on the energy separation between the exciton and the normal mode resonance. In addition, for an inhomogeneous broadened system, pronounced oscillations in the intensity of the optical field or the total induced optical polarization no longer imply a similar oscillatory coherent energy exchange between excitons and cavity photons.

Rapid fetal lung maturity testing: commercial versus NBD-phosphatidylcholine assay.

We compared the TDx Fetal Lung Maturity test and the fluorescence polarization method using 1-palmitoyl-2(6-[(7-nitro-2,1,3-benzoxadiazol-4- yl)amino]caproyl)phosphatidylcholine (NBD-phosphatidylcholine). Using 76 paired human amniotic fluid samples, the fluorescence polarization values of the two methods were found to have a strong nonlinear correlation (r2 = 0.946). Both assays can be completed in less than 1 hour, have excellent precision (between-day variation less than 2%), and indicate the amount of surfactant phospholipid relative to albumin. The FLM assay is calibrated with surfactant/albumin standards; therefore, the reported results (in mg/g) correlate inversely with polarization of NBD-phosphatidylcholine. Strong correlations were seen for both assays with the lecithin-sphingomyelin ratio and phosphatidylglycerol. The correlations indicate that the recommended reference range for FLM will have more false predictions of immaturity than the NBD-phosphatidylcholine assay.

Measuring the number of lamellar body particles in amniotic fluid.

We describe a method for determining the number and size distribution of lamellar bodies and compare the results prospectively with other tests for fetal lung maturity: lecithin-sphingomyelin ratio (L/S), phosphatidylglycerol, and fluorescence polarization. The technique uses an electronic particle counter calibrated for a size range of 1.7-7.3 fL. The number of lamellar bodies in amniotic fluid samples varied from 3800-166,000 particles per microliter and correlated strongly with L/S ratio (r = 0.75; N = 144) and fluorescence polarization (r = -0.78; N = 165). Amniotic fluid samples stored for up to 10 days at 4C had stable lamellar body counts (within +/- 11%). Longer storage tended to decrease the counts. Addition of more than 1% (v/v) whole blood significantly decreased the lamellar body counts. This technique shows promise for the rapid assessment of fetal lung maturity.

Lamellar body counts for rapid fetal lung maturity testing.

OBJECTIVE: To evaluate amniotic fluid lamellar body counting as a fetal lung maturity test. Lamellar body particles can be rapidly counted using the platelet channel of most blood cell analyzers. METHODS: We conducted a 3-year prospective clinical outcome study. During the interval under study, outcomes of 247 neonates were used to evaluate the test; 28 neonates developed respiratory distress syndrome (RDS). Lecithin-sphingomyelin ratio (L/S) was available for 187 cases. RESULTS: All cases of RDS had lamellar body counts of 55,000/microL or less and L/S of 2.2 or less; 59% of cases with no RDS had counts greater than 55,000/microL and 70% of normal cases had L/S higher than 2.2. CONCLUSION: Use of lamellar body counts is justified as a rapid screening test to predict fetal lung maturity. Immature results should be followed by a more specific test such as L/S.

From the clinic to the research laboratory. The role of the clinician in molecular genetic studies.

BACKGROUND: The first physician to examine a patient with a genetic disorder or birth defect is usually a specialist in a field other than genetics. The presentation of certain categories of patients of particular interest to molecular genetics research may be distinct. The recognition of these patients by clinicians is fundamental to the study of genetic disorders at the DNA level. OBSERVATIONS: Neurofibromatosis type 1 is a paradigm for how the study of a single genetic disease and its multiple molecular features has been facilitated by the use of various categories of patients. Other examples of interest to dermatologists, surgeons, and other specialists are discussed to demonstrate how the identification of key patients was instrumental in studies of gene localization and subsequent cloning, gene clusters or contiguous gene deletion syndromes, or mutation phenomena such as imprinting, uniparental disomy, and gonadal mosaicism. The molecular researcher has limited access to surgical specimens, and the donation of skin, tumor, and other tissues may lead to increased knowledge of new mutations in somatic mosaicism, or loss of heterozygosity of tumor suppression genes in cancer. CONCLUSIONS: Guidelines are suggested to alert the physician to each of these categories of individuals with unusual presentation, as well as to recognize that the study of families with rare disorders may enable scientists to locate the responsible genes. The teamwork of clinician and molecular researcher is essential for the advancement of our understanding of DNA mechanisms in genetic disease. The ethics involved in referral of patients to molecular genetic research studies are discussed.

Holistic processes in the perception and transformation of disoriented figures.

Two experiments tested whether mental rotation of complex, hierarchical stimuli occurs holistically or separately at global and local levels of structure. Large (global) letters were constructed from spatial arrangements of small (local) letters. Reflection conditions (normal vs. reflected) were produced by varying the two levels independently. The task was structured so that subjects could rotate one level of the stimulus in some conditions but had to rotate both levels in other conditions. Experiment 1 showed that rotation rate was not affected by the number of levels that had to be rotated to make a reflection decision. This result implies that the rotation of global and local levels occurred together rather than sequentially. Experiment 2 showed that the rotation of the two levels was holistic as opposed to parallel and independent. The results also demonstrate that global information is processed faster than local information regardless of whether or not a rotation is performed. These findings are discussed in relation to theories of mental rotation and global precedence.

Configural effects in perceived pointing of ambiguous triangles.

Five experiments examined the influence of configural variables on perceived pointing of ambiguous (equilateral) triangles. The amount of time required to see the triangles point in specified directions was measured for single triangles and linear configurations of multiple triangles. The results show that perceived pointing is biased toward directions that are coincident with or perpendicular to the configural line. Perceptual interference occurs when the configural line biases pointing away from the correct direction, and facilitation sometimes occurs when it biases pointing toward the correct direction. The magnitude of interference increases (a) when the required direction is perceptually less salient, (b) when the configural line contains more triangles, and (c) when the triangles are closer together. Further results suggest that the spacing effect depends on relative rather than absolute distance and that the number and spacing effects are additive. In addition, substantial differences were found among individuals in terms of their susceptibility to configural interference. These results are discussed in terms of a sequential sampling model of perceived pointing. The samples result from spontaneous alternations in a multistable system of three mutually inhibitory directional subsystems. It is proposed that configural effects arise from low resolution pattern information that influences the behavior of the multistable system. Possible mechanisms are suggested through which directional, attentional, and individual differences might also arise.

Textural effects in perceived pointing of ambiguous triangles.

Five experiments examined the influence of textural stripes on perceived pointing of ambiguous (equilateral) triangles. Reaction times for discriminating specific directions of pointing were measured for plain triangles and for triangles containing stripes that were either coincident with or perpendicular to one of the three possible directions of pointing. Perceptual interference occurred when the stripes biased a direction other than one specified by the discrimination task. The magnitude of the interference decreased (a) as the environmental salience of the specified direction increased and (b) as the spatial frequency of the stripes increased. Further results indicated that this frequency effect is relative to the size of the triangle; it is not determined by absolute (retinal) frequency. Stripes in the ground region surrounding the triangle also produced interference. However, this interference decreased as the region around the triangle was cleared of stripes. The results are discussed in terms of factors that determine the qualitative and quantitative nature of the interference effect, particularly symmetry and spatial frequency.

Separability and integrality of global and local levels of hierarchical patterns.

We used a constrained classification task to examine the perceptual relations between global and local levels in hierarchical patterns composed of many, relatively small elements and those composed of few, relatively large elements. In Experiments 1 and 3 subjects were asked to make classifications based on "form" or "texture." In Experiments 2 and 4 they were asked to classify according to the "shape" of the configuration or the elements. The results indicate that configural and elemental levels are perceptually separable for many-element patterns when processed as form and texture: Subjects could attend to either level without being affected by variation along the irrelevant dimension. However, when the same many-element patterns were processed for global and local shape, subjects could not selectively attend to either level. For few-element patterns, global configuration and local elements appeared to be perceptually integral dimensions. These results are relevant to two issues: the global precedence hypothesis and the explanations of integral and separable dimensions.

Form and texture in hierarchically constructed patterns.

Perceived organization of hierarchically constructed patterns was investigated through similarity judgments and a verbal description task. The number of elements and their sizes relative to the configuration were varied in a series of five experiments. The results show that in patterns composed of a few relatively large elements, the elements are perceived as individual parts of the overall form and are perceptually salient. Increasing the number of elements and/or decreasing their size results in a perceived unified form associated with texture, representing the structural properties of the elements as a group. In the latter case, the perceptual salience of the individual element decreases and the global form (or sometimes the texture) dominates perception. These findings suggest that the perceptual levels arising from global configuration of local elements may not correspond directly to these two geometrical levels in the stimulus domain as much previous work on "global versus local" processing has assumed. Rather, the mapping of the two independent geometrical levels into meaningful perceptual levels depends critically on the number and relative size of the elements, thus changing the perceived organization of the whole pattern.

Organizational factors in perceived dimensionality.

The hypothesis that perceived dimensionality of projection drawings is influenced by perceived organization was tested in two experiments. Organization was biased by coloration: The drawings were (a) uncolored, (b) colored in ways that emphasized plausible three-dimensional parts of the represented objects, or (c) colored in ways that emphasized two-dimensional (2D) parts of the drawings themselves. In Experiment 1, subjective ratings of three-dimensionality (3D) were greater for the 3D-biased stimuli than for the unbiased stimuli, and ratings for the 2D-biased stimuli were lower than for the unbiased stimuli. Similar results were obtained in Experiment 2 in which latencies to perceive the drawings three-dimensionally were measured. The 3D-biased stimuli were seen in depth more quickly than the unbiased stimuli, and the 2D-biased stimuli were seen in depth more slowly than the unbiased stimuli. Additional results on the relation between ratings and latencies suggest that latencies are affected more strongly by object complexity than are ratings.

Orientation and symmetry: effects of multiple, rotational, and near symmetries.

Time to detect bilateral symmetry in different orientations was studied for closed polygons with single, double, quadruple, rotational, and near symmetry. In Experiment 1, the orientation of the axis of symmetry was varied. Detection was fastest for vertical symmetry, next fastest for horizontal, and slowest for left- and right-diagonal symmetries. For corresponding orientations, responses were faster to quadruple than double symmetries, and faster to double than single symmetries. Negative responses to nearly symmetric figures produced an orientation effect similar to that for single symmetries. Rotational symmetries showed no orientation effect and took longer to reject than near symmetries. In Experiment 2, subjects looked only for vertical symmetry. Responses were twice as fast as in comparable conditions of Experiment 1. The effect of multiple symmetries was still present, but rotational symmetries were rejected faster than near symmetries. The results are interpreted as supporting a dual process model for detecting symmetry in multiple orientation channels: Observers first select potential axes of symmetry defined by mirror-similar parts and then evaluate specific axes sequentially in a detailed comparison for mirror-identity.

Reference frames in mental rotation.

Four experiments are reported that investigate whether images or reference frames are transformed during a mental rotation task. In all experiments a display of four identical letters (P1) was presented at either +90 degrees or -90 degrees from upright, and subjects had to decide whether the letters were normal or mirror-image reflections. A single letter (P2) was then presented 100 ms later in a variable orientation with the same task instructions. Reaction times to P2 were assessed to determine whether an image of P2 was rotated to upright or whether an internal reference frame was rotated into congruence with P2 from the orientation of P1. The results as a whole suggest that transformations of P2 can be initiated either relative to upright or relative to the orientation of P1. They further indicate that the probability of using each reference orientation can be changed by procedural variations. The findings are most parsimoniously interpreted as suggesting that mental rotation involves the transformation of reference frames rather than the transformation of template-like representations.

Late influences on perceptual grouping: Amodal completion.

Perceptual grouping is generally assumed to be an early visual process that operates on a previously unorganized image-based representation. The present experiment shows that elements perceived as occluded by a closer surface tend to be grouped with elements having the same shape as the amodally completed percept rather than with those having the same retinal shape as the incomplete stimulus. It is therefore concluded that perceptual grouping by shape similarity either occurs after amodal completion or is a temporally extended process that occurs both before and after it.