Contribution of large scale biases in decoding of direction-of-motion from high-resolution fMRI data in human early visual cortex.

Previous studies have demonstrated that the perceived direction of motion of a visual stimulus can be decoded from the pattern of functional magnetic resonance imaging (fMRI) responses in occipital cortex using multivariate analysis methods (Kamitani and Tong, 2006). One possible mechanism for this is a difference in the sampling of direction selective cortical columns between voxels, implying that information at a level smaller than the voxel size might be accessible with fMRI. Alternatively, multivariate analysis methods might be driven by the organization of neurons into clusters or even orderly maps at a much larger scale. To assess the possible sources of the direction selectivity observed in fMRI data, we tested how classification accuracy varied across different visual areas and subsets of voxels for classification of motion-direction. To enable high spatial resolution functional MRI measurements (1.5mm isotropic voxels), data were collected at 7T. To test whether information about the direction of motion is represented at the scale of retinotopic maps, we looked at classification performance after combining data across different voxels within visual areas (V1-3 and MT+/V5) before training the multivariate classifier. A recent study has shown that orientation biases in V1 are both necessary and sufficient to explain classification of stimulus orientation (Freeman et al., 2011). Here, we combined voxels with similar visual field preference as determined in separate retinotopy measurements and observed that classification accuracy was preserved when averaging in this 'retinotopically restricted' way, compared to random averaging of voxels. This insensitivity to averaging of voxels (with similar visual angle preference) across substantial distances in cortical space suggests that there are large-scale biases at the level of retinotopic maps underlying our ability to classify direction of motion.

Quantitative genetics of age-related retinal degeneration: a second F1 intercross between the A/J and C57BL/6 strains.

PURPOSE: Previously, several quantitative trait loci (QTL) that influence age-related retinal degeneration (ageRD) were demonstrated in a cross between the C57BL/6J-c(2J) and BALB/cByJ strains (B x C). In this study, as a complementary approach to ongoing recombinant progeny testing for the purpose of identifying candidate quantitative trait genes (QTG), a second test cross using the A/J and the pigmented C57BL/6J strains (A x B) was carried out. The albino A/J strain was selected because it had the most amount of ageRD among several inbred strains tested, and the pigmented C57BL/6J strain was selected because along with its coisogenic counterpart C57BL/6J-c(2J) it had the least amount of ageRD. Thus, the effect of pigment on ageRD could be tested at the same time that the C57BL/6 genetic background was kept in common between the crosses from the two studies for the purpose of comparison. METHODS: A non-reciprocal F1 intercross between the A/J and C57BL/6J strains produced 170 F2 progeny. At 8 months of age after being maintained in relatively dim light, F2 mice, control mice and mice of other strains were evaluated for retinal degeneration by measurement of the thickness of the outer nuclear layer of the retina. The F2 mice were genotyped with dinucleotide repeat markers spanning the genome. Correlation of genotype with phenotype was made with Map Manager QTX software. RESULTS: Comparison of several strains of mice including the pigmented strains 129S1/SvImJ and C57BL/6J and the albino strains A/J, NZW/LacJ, BALB/cByJ and C57BL/6J-c(2J), showed significant differences in ageRD. The greatest difference was between the albino A/J strain and the pigmented C57BL/6J strain. However, there was no significant difference between the pigmented C57BL/6J and its albino coisogenic counterpart C57BL/6J-c(2J). Neither was there significant difference between the pigmented and albino F2 mice from the A x B cross. On the other hand, F2 males had a small but significantly lower amount of ageRD than females. Several QTL were identified in the A x B cross but surprisingly none of the 3 major QTL present in the original B x C cross (Chrs 6, 10, and 16) was present. There were minor QTL on proximal Chr 12 and proximal Chr 14 in common between the two crosses, and the proximal Chr 12 QTL was present in a previous light damage study involving the B and C strains. At least one sex-limited QTL was present on the X chromosome with a peak in a different location from that of a sex-limited QTL in the previous B x C study. In addition, the protective X allele was from the BALB/cByJ strain in the B x C cross and from C57BL/6J in the A x B cross. In both crosses, the C57BL/6J X-chromosome allele was recessive. CONCLUSIONS: Significant differences were observed in ageRD among several inbred strains of mice maintained in relatively dim light. AgeRD was not influenced by pigment but was influenced by gender, albeit to a small degree. The presence of the same QTL in one light-induced and two ageRD studies suggests at least partial commonality in retinal degeneration pathways of different primary cause. However, the three main QTL present in the B x C cross were absent from the A x B cross. This suggests that the genetic determinants responsible for the greater sensitivity to ageRD of BALB/cByJ and A/J relative to C57BL/6J are not the same. This is supported by the presence of sex-limited X-chromosome QTL in the two crosses in which the C57BL/6J allele is protective relative to the A allele and sensitive relative to the C allele. The findings in the two studies of differing allelic relationships of QTG, and differing QTL aid the identification of candidate genes mapping to critical QTL. Identifying natural modifying genes that influence retinal degeneration resulting from any causal pathway, especially those QTG that are protective, will open avenues of study that may lead to broad based therapies for people suffering retinal degenerative diseases.

Selective mechanisms for complex visual patterns revealed by adaptation.

A great deal is known about the initial steps of visual processing. We know that humans have neural mechanisms selectively tuned to simple patterns of particular spatial frequencies and orientations. We also know that much later in the visual pathway, in inferotemporal cortex, cells respond to extremely complex visual patterns such as images of faces. Very little is known about intermediate levels of visual processing, where early visual signals are presumably combined to represent increasingly complex visual features. Here we show the existence of visual mechanisms in humans, tuned and selective to particular combinations of simple sinusoidal patterns, using a novel method of compound adaptation.

Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects.

We recently mapped two quantitative trait loci that have widespread effects on hippocampal architecture in mouse: Hipp1a and Hipp5a. We also noted remarkable strain differences in the relative sizes of different hippocampal regions. Estimated heritable variation for these differences was 42% in hippocampus proper, 40% in dentate gyrus, 31% in granule cell layer and 18% in pyramidal cell layer. Region size varied at least 50% from largest to smallest measurement. Here we have utilized these differences to identify loci with effects on the dentate gyrus, granule cell layer, hippocampus proper and pyramidal cell layer. Our sample consists of C57BL/6J and DBA/2J and 32 BXD recombinant inbred strains. Volumetric data were corrected for shrinkage and for differences in brain weight. We identified significant loci on chromosomes (Chr) 6, 13 and 15, and a significant interaction locus on proximal Chr 11. A suggestive distal Chr 1 locus overlaps with Hipp1a. HipV13a (Chr 13, 42-78Mb) has an additive effect of 0.56 mm3 (12.1%) on dentate gyrus volume, while GrV6a (Chr 6, 29-65 Mb) has additive effects of 0.14 mm3 (16.0%) on the volume of the granule cell layer. HipV13a also interacts with DGVi11a, a locus on proximal Chr 11 that operates exclusively through its epistatic effect on HipV13a and has no independent main effect HipV15a (Chr 15, 0-51 Mb) has an additive effect of 1.76 mm3 (9.0%) on the volume of the hippocampus proper. We used WebOTL, a recently described web-based tool, to examine genetic correlation of gene expression with hippocampal volume. We identified a number of genes that map within the OTL intervals and have highly correlated expression patterns. Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response.

Consumption of biogenic nitric oxide in hydrated soil.

An experimental study was conducted in order to determine the relationship of nitric oxide (NO) consumption to water-filled pore space in soil. A test system that included the capability to blend gases, test soil samples, and analyze off-gases was used to conduct the study. The experimental set consisted of three replicates at five different levels of soil water content and three different levels of soil nitrogen in a sandy loam soil: unamended soil, soil fertilized at 56.2 kg N per ha (50 lb N acre(-1)), and soil fertilized at 112.3 kg N per ha (100 lb N acre(-1)). The average NO consumption rates were 7.1x10(-13) g-NO cm(-3) soil, 3.5x10(-11) g-NO cm(-3) soil, and 1.5x10(-10) g-NO cm(-3) soil, respectively.

Sheep don't forget a face.

The human brain has evolved specialized neural mechanisms for visual recognition of faces, which afford us a remarkable ability to discriminate between, remember and think about many hundreds of different individuals. Sheep also recognize and are attracted to individual sheep and humans by their faces, as they possess similar specialized neural systems in the temporal and frontal lobes for assisting in this important social task, including a greater involvement of the right brain hemisphere. Here we show that individual sheep can remember 50 other different sheep faces for over 2 years, and that the specialized neural circuits involved maintain selective encoding of individual sheep and human faces even after long periods of separation.

Human face recognition in sheep: lack of configurational coding and right hemisphere advantage.

Face recognition in sheep is qualitatively similar to that in humans in terms of its left visual field bias, and the effects of expertise and configural coding. The current study was designed to determine whether such effects are species specific by investigating the case of sheep recognising humans. It was found that the sheep could identify human faces and while they showed a small inversion-induced decline in discriminatory performance, this was significantly less than seen with sheep faces. In other aspects, there were qualitative differences with human face recognition compared with conspecific recognition. In contrast with sheep faces there was no left visual field advantage in the recognition of human faces and the internal features were not used at all as visual cues. The data suggest that these sheep, whilst being extensively exposed to interactions with humans, were unable to identify them with all the same 'expert' methods as were used to discriminate other sheep. This suggests that different neural systems may, to some extent, be used for recognition of sheep as opposed to human faces. The relative contribution to differential neural processing of the faces of the different species and the role of expertise are discussed.

Hurricane-loaded soil: effects on nitric oxide emissions from soil.

The nitric oxide (NO) flux from eastern North Carolina soils subjected to flooding from hurricanes were studied in laboratory experiments. Three sites along the Neuse River basin in eastern North Carolina that sustained different intensities of flooding in September 1999 from Hurricane Floyd were examined. Hurricane Floyd impacted the Neuse River basin by inducing flooding that damaged and disabled hog (Sus scrofa) lagoons and municipal wastewater treatment plants. Between approximately 53 and 325 million liters (14 and 86 million gallons) of untreated hog waste and between approximately 5.7 and 34.4 billion liters (1.5 and 9.1 billion gallons) of untreated municipal wastewater are projected to have entered the Neuse River basin, increasing the concentrations of nitrogen (N), phosphorus (P), and total solids. Phosphorus and total solids are projected to have increased 3.2 and 199.2 mg/L, respectively. Total N was projected to have increased by 9.8 mg/L, which is posited to have increased the NO flux from flooded soils for months after the hurricane. Nitric oxide emissions from soil can adversely affect ozone levels in the lower troposphere. Minimization of NO flux from soil is advantageous, protecting air quality as well as conserving valued nitrogen fertilizers. Hurricane-loaded soils were found to produce more than 30 times greater NO emissions than nonflooded soils with NO fluxes ranging from 0.1 to 102.5 ng N/(m2 s).

Using the free-to-total prostate-specific antigen ratio to detect prostate cancer in men with nonspecific elevations of prostate-specific antigen levels.

BACKGROUND: Prostate-specific antigen (PSA) levels between 4.0 to 10.0 ng/ml have poor specificity in prostate cancer screening, leading to unnecessary biopsies. OBJECTIVE: To determine whether the free-to-total PSA ratio (F/T PSA) improved the diagnostic accuracy of these nonspecific PSA levels. MEASUREMENTS AND MAIN RESULTS: MEDLINE searchedwas from 1986 to 1997. Additional studies were identified from article bibliographies and by searching urology journals. Two investigators independently identified English-language studies providing F/T PSA ratio test-operating characteristics data on > or = 10 cancer patients with PSA values between 2.0 and 10.0 ng/ml. Twenty-one of 90 retrieved studies met selection criteria. Two investigators independently extracted data on methodology and diagnostic performance. Investigator-selected cut points for the optimal F/T PSA ratio had a median likelihood ratio of 1.76 (interquartile range, 1.40 to 2.11) for a positive test and 0.27 (0.20 to 0.40) for a negative test. Assuming a 25% pretest probability of cancer, the posttest probabilities were 37% following a positive test and 8% following a negative test. The summary receiver operating characteristic curve showed that maintaining test sensitivity above 90% was associated with false positive rates of 60% to 90%. Methodologic problems limited the validity and generalizability of the literature. CONCLUSIONS: A negative test reduced the posttest probability of cancer to approximately 10%. However, patients may find that this probability is not low enough to avoid undergoing prostate biopsy. The optimal F/T PSA ratio cut point and precise estimates for test specificity still need to be determined.

The paradox of physicians and administrators in health care organizations.

Rapidly changing times in health care challenge both physicians and health care administrators to manage the paradox of providing orderly, high quality, and efficient care while bringing forth innovations to address present unmet problems and surprises that emerge. Health care has grown throughout the past several centuries through differentiation and integration, becoming a highly complex biological system with the hospital as the central attractive force--or "strange attractor"--during this century. The theoretical model of complex adaptive systems promises more effective strategic direction in addressing these chaotic times where the new strange attractor moves beyond the hospital.

Configurational coding, familiarity and the right hemisphere advantage for face recognition in sheep.

This study examined characteristics of visual recognition of familiar and unfamiliar faces in sheep using a 2-way discrimination task. Of particular interest were effects of lateralisation and the differential use of internal (configurational) vs external features of the stimuli. Animals were trained in a Y-maze to identify target faces from pairs, both of which were familiar (same flock as the subjects) or both of which were unfamiliar (different flock). Having been trained to identify the rewarded face a series of stimuli were presented to the sheep, designed to test for the use of each visual hemifield in the discriminations and the use of internal and external facial cues. The first experiment showed that there was a left visual hemifield (LVF) advantage in the identification of 'hemifaces', and 'mirrored hemifaces' and 'chimeric' faces and that this effect was strongest with familiar faces. This represents the first evidence for visual field bias outside the primate literature. Results from the second experiment showed that, whilst both familiar and unfamiliar faces could be identified by the external features alone, only the familiar faces could be recognised by the internal features alone. Overall the results suggest separate recognition methods for socially familiar and unfamiliar faces, with the former being coded more by internal, configurational cues and showing a lateral bias to the left visual field.

A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.

CONTEXT: Adverse drug events (ADEs) are the most common type of iatrogenic injury occurring in hospitalized patients. Errors leading to ADEs are often due to restricted availability of information at the time of physician order writing. OBJECTIVES: To develop, implement, and evaluate a computer alert system designed to correct errors that might lead to ADEs and to detect ADEs before maximum injury occurs. DESIGN: Prospective case series. SETTING: A 650-bed community teaching hospital in Phoenix, Ariz. PATIENTS: Consecutive sample of 9306 nonobstetrical adult patients admitted during the last 6 months of 1997. INTERVENTIONS: Thirty-seven drug-specific ADEs were targeted. Our hospital information system was programmed to generate alerts in clinical situations with increased risk for ADE-related injury. A clinical system was developed to ensure physician notification of alerts. MAIN OUTCOME MEASURES: A true-positive alert was defined as one in which the physician wrote orders consistent with the alert recommendation after alert notification. RESULTS: During the 6-month study period, the alert system fired 1116 times and 596 were true-positive alerts (positive predictive value of 53%). The alerts identified opportunities to prevent patient injury secondary to ADEs at a rate of 64 per 1000 admissions. A total of 265 (44%) of the 596 true-positive alerts were unrecognized by the physician prior to alert notification. CONCLUSIONS: Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.

A major influence of sex-specific loci on alcohol preference in C57Bl/6 and DBA/2 inbred mice.

C57Bl/6 mice reproducibly prefer to ingest more 10% ethanol in a two-bottle choice paradigm than do DBA/2J mice. In this paper we report the identification of two new sex-specific alcohol preference (Alcp) loci. Melo and associates (1996) identified two loci: Alcp1, a male-specific locus on Chromosome (Chr) 2, and Alcp2, a female- and cross-specific locus on Chr 11. We have additionally identified Alcp3, a male-specific locus on Chr 3, and Alcp4, a female-specific locus on Chr 1. We have also performed a statistical analysis to exclude the possibility of undiscovered major alcohol preference loci that are not sex-specific in our backcross paradigm. Our results indicate that alcohol preference in C57BL/6 mice, as measured in our backcross, is largely controlled in a sex-specific manner.