Dynamic Modulation of Cortical Excitability during Visual Active Sensing.

Visual physiology is traditionally investigated by presenting stimuli with gaze held constant. However, during active viewing of a scene, information is actively acquired using systematic patterns of fixations and saccades. Prior studies suggest that during such active viewing, both nonretinal, saccade-related signals and "extra-classical" receptive field inputs modulate visual processing. This study used a set of active viewing tasks that allowed us to compare visual responses with and without direct foveal input, thus isolating the contextual eye movement-related influences. Studying nonhuman primates, we find strong contextual modulation in primary visual cortex (V1): excitability and response amplification immediately after fixation onset, transiting to suppression leading up to the next saccade. Time-frequency decomposition suggests that this amplification and suppression cycle stems from a phase reset of ongoing neuronal oscillatory activity. The impact of saccade-related contextual modulation on stimulus processing makes active visual sensing fundamentally different from the more passive processes investigated in traditional paradigms.

Top-down, contextual entrainment of neuronal oscillations in the auditory thalamocortical circuit.

Prior studies have shown that repetitive presentation of acoustic stimuli results in an alignment of ongoing neuronal oscillations to the sequence rhythm via oscillatory entrainment by external cues. Our study aimed to explore the neural correlates of the perceptual parsing and grouping of complex repeating auditory patterns that occur based solely on statistical regularities, or context. Human psychophysical studies suggest that the recognition of novel auditory patterns amid a continuous auditory stimulus sequence occurs automatically halfway through the first repetition. We hypothesized that once repeating patterns were detected by the brain, internal rhythms would become entrained, demarcating the temporal structure of these repetitions despite lacking external cues defining pattern on- or offsets. To examine the neural correlates of pattern perception, neuroelectric activity of primary auditory cortex (A1) and thalamic nuclei was recorded while nonhuman primates passively listened to streams of rapidly presented pure tones and bandpass noise bursts. At arbitrary intervals, random acoustic patterns composed of 11 stimuli were repeated five times without any perturbance of the constant stimulus flow. We found significant delta entrainment by these patterns in the A1, medial geniculate body, and medial pulvinar. In A1 and pulvinar, we observed a statistically significant, pattern structure-aligned modulation of neuronal firing that occurred earliest in the pulvinar, supporting the idea that grouping and detecting complex auditory patterns is a top-down, context-driven process. Besides electrophysiological measures, a pattern-related modulation of pupil diameter verified that, like humans, nonhuman primates consciously detect complex repetitive patterns that lack physical boundaries.

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo.

Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols.

Sustainable production of housefly (Musca domestica) larvae as a protein-rich feed ingredient by utilizing cattle manure.

The common housefly, Musca domestica, is a considerable component of nutrient recycling in the environment. Use of housefly larvae to biodegrade manure presents an opportunity to reduce waste disposal while the rapidly assimilated insect biomass can also be used as a protein rich animal feed. In this study, we examine the biodegradation of dairy cattle manure using housefly larvae, and the nutritional value of the resulting larva meal as a feed ingredient. Our results demonstrated that dairy cattle manure presents a balanced substrate for larval growth, and the spent manure showed reductions in concentration of total nitrogen (24.9%) and phosphorus (6.2%) with an overall reduction in mass. Larva yield at an optimum density was approximately 2% of manure weight. Nutritional analysis of M. domestica larva meal showed values comparable to most high protein feed ingredients. Larva meal was 60% protein with a well-balanced amino acid profile, and 20% fat with 57% monounsaturated fatty acids, and 39% saturated fatty acids. Larva meal lacked any significant amount of omega-3 fatty acids. Evaluation of micronutrients in larva meal suggested that it is a good source of calcium and phosphorus (0.5% and 1.1% respectively). The nutritional value of larva meal closely matches that of fishmeal, making it a potentially attractive alternative for use as a protein-rich feed ingredient for livestock and aquaculture operations.

Validity and reliability of a novel patient reported outcome tool to evaluate post-operative dysphagia, odynophagia, and voice (DOV) disability after anterior cervical procedures.

BACKGROUND: Existing evaluative instruments for dysphagia, odynophagia, and voice disturbance are cumbersome, focus pre-dominately on dysphagia, and often require administration by a certified Speech Pathologist. This study was conducted to utilize widely accepted instruments such as the American Speech and Hearing Association's National Outcomes Measurement System (NOMS) and VAS pain scales to validate a novel, patient-reported instrument that quantifies the severity of post-operative dysphagia, odynophagia, and voice disabilities (DOV). METHODS: The DOV was developed and subjected to multiple rounds of face and content validation by representative patient cohorts and a panel of clinical experts. An established, prospective clinical registry was utilized to collect pre and post-operative VAS-swallow related pain and DOV measurements for subjects with recent anterior cervical procedures (n=25 content validation, n=20 criterion validation), or recent lumbar decompressions (n=33). NOMS evaluations were performed by a certified Speech Language Pathologist on the first post-operative day after minimally invasive anterior approaches to cervical reconstruction were performed in the criterion validation cohort. RESULTS: Content validity: Subjects with a recent anterior cervical procedure reported a significant increase in post-operative dysphagia (pre-op: 0.13±0.35, post-op: 1.08±1.41, p=0.01), odynophagia (pre-op: 0.24±0.69, post-op: 0.84±0.90, p=0.001), and voice (pre-op: 0.10±0.41, post-op: 0.88±0.92, p=0.0004) disturbance. In contrast, subjects with a recent lumbar procedure did not demonstrate a significant increase in post-operative dysphagia, odynophagia, or voice disturbance (p>0.05).Criterion validity: Chi-squared contingency testing for independence between converted NOMS and DOV instrument scores accepted linkage between the two instruments for dysphagia X2(DF: 12, n=20, Expected: 21.03, Observed: 24.4, p: 0.02) and voice X2(DF: 6, n=20, Expected: 12.60, Observed: 21.28, p: 0.002) dimensions. Similarly, converted swallow related VAS and DOV odynophagia instruments demonstrated linkage X2(DF: 9, n=20, Expected: 16.92, Observed: 24.21, p: 0.004).Internal Reliability: Chronbach's alpha coefficient of reliability was 0.74 between all DOV survey dimensions. CONCLUSIONS: The DOV survey is a valid patient-reported instrument to rapidly and reliably detect post-operative swallow and voice dysfunction.

Global dynamics of selective attention and its lapses in primary auditory cortex.

Previous research demonstrated that while selectively attending to relevant aspects of the external world, the brain extracts pertinent information by aligning its neuronal oscillations to key time points of stimuli or their sampling by sensory organs. This alignment mechanism is termed oscillatory entrainment. We investigated the global, long-timescale dynamics of this mechanism in the primary auditory cortex of nonhuman primates, and hypothesized that lapses of entrainment would correspond to lapses of attention. By examining electrophysiological and behavioral measures, we observed that besides the lack of entrainment by external stimuli, attentional lapses were also characterized by high-amplitude alpha oscillations, with alpha frequency structuring of neuronal ensemble and single-unit operations. Entrainment and alpha-oscillation-dominated periods were strongly anticorrelated and fluctuated rhythmically at an ultra-slow rate. Our results indicate that these two distinct brain states represent externally versus internally oriented computational resources engaged by large-scale task-positive and task-negative functional networks.

Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant.

UNLABELLED: Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts. SIGNIFICANCE STATEMENT: Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants.

Auditory properties in the parabelt regions of the superior temporal gyrus in the awake macaque monkey: an initial survey.

The superior temporal gyrus (STG) is on the inferior-lateral brain surface near the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical region, the "parabelt," which is part of a network of inferior temporal areas subserving communication and social cognition as well as object recognition and other functions. However, due to its location beneath the squamous temporal bone and temporalis muscle, the STG, like other inferior temporal regions, has been a challenging target for physiological studies in awake-behaving macaques. We designed a new procedure for implanting recording chambers to provide direct access to the STG, allowing us to evaluate neuronal properties and their topography across the full extent of the STG in awake-behaving macaques. Initial surveys of the STG have yielded several new findings. Unexpectedly, STG sites in monkeys that were listening passively responded to tones with magnitudes comparable to those of responses to 1/3 octave band-pass noise. Mapping results showed longer response latencies in more rostral sites and possible tonotopic patterns parallel to core and belt areas, suggesting the reversal of gradients between caudal and rostral parabelt areas. These results will help further exploration of parabelt areas.

Approach to the adult hospitalized patient on an insulin pump.

Patients on continuous subcutaneous insulin infusion, or insulin pumps, are increasingly seen in hospitals. Inpatient providers need to have a working knowledge of insulin pumps to be able to decide, in conjunction with the patient whenever feasible, whether or not pump use is to be continued in the hospital, to assist patients in adjusting insulin doses via continuous subcutaneous insulin infusion, to transition patients to multiple daily subcutaneous insulin dosing as appropriate, and to prevent or manage problems that might arise from improper handling of the insulin pump. Clinical vignettes with key points and strategies for patient care are discussed in this article.

System-wide learning from root cause analysis: a report from the New South Wales Root Cause Analysis Review Committee.

BACKGROUND: Preventable errors are common in healthcare. Over the last decade, Root Cause Analysis (RCA) has become a key tool for healthcare services to investigate adverse events and try to prevent them from happening again. The purpose of this paper is to highlight the work of the New South Wales (NSW) RCA Review Committee. The benefits of correctly classifying, aggregating and disseminating RCA data to clinicians will be discussed. In NSW, we perform an average of 500 RCAs per year. It is estimated that each RCA takes between 20 and 90 h to perform. In 2007, the NSW Clinical Excellence Commission (CEC) and the Quality and Safety Branch at the Department of Health constituted an RCA review committee. 445 RCAs were reviewed by the committee in 14 months. 41 RCAs were related to errors in managing acute coronary syndrome. RESULTS AND DISCUSSION: The large number of RCAs has enabled the committee to identify emerging themes and to aggregate the information about underlying human (staff), patient and system factors. The committee has developed a taxonomy based on previous work done within health and aviation and assesses each RCA against this set of criteria. The effectiveness of recommendations made by RCA teams requires further review. There has been conjecture that staff do not feel empowered to articulate root causes which are beyond the capacity of the local service to address. CONCLUSION: Given the number of hours per RCA, it seems a shame that the final output of the process may not in fact achieve the desired patient safety improvements.

Variability among four laboratories of the filter bag technique to determine acid and neutral detergent fiber contents in ruminant feeds from Argentina.

The objective of this work was to evaluate the filter bag technique (FBT) in an ANKOM 200 fiber analyzer to assess its accuracy for the determination of acid and neutral detergent fiber (ADF and NDF, respectively) contents in common ruminant feeds from the temperate region of Argentina. The evaluation was done in a ring test of 4 laboratories. The 3 Argentine laboratories were from the College of Agronomy, University of Buenos Aires, the College of Agricultural Sciences of the Catholic University of Argentina, and the Balcarce Agricultural Experiment Station of the National Institute of Agricultural Technology (INTA). The fourth laboratory was from the Department of Animal Science of Cornell University, Ithaca, NY. The feeds utilized were soybean meal expeller, whole sunflower seed, corn grain, herbages of alfalfa, ryegrass, tall wheatgrass, weeping lovegrass, guinea and barley grasses, and silages of corn and of a natural grassland. Results indicated that values obtained in the 4 laboratories were consistent regardless of the laboratory where the analyses were performed. It was concluded that the FBT in the ANKOM instrument gave satisfactory results when used for the determination of both ADF and NDF across samples having a wide range of fiber contents, and that the among-laboratories variability of this methodology was low.

Perturbation of the small intestine microbial ecology by streptomycin alters pathology in a Salmonella enterica serovar typhimurium murine model of infection.

The small intestine is an important site of infection for many enteric bacterial pathogens, and murine models, including the streptomycin-treated mouse model of infection, are frequently used to study these infections. The environment of the mouse small intestine and the microbiota with which enteric pathogens are likely to interact, however, have not been well described. Therefore, we compared the microbiota and the concentrations of short-chain fatty acids (SCFAs) present in the ileum and cecum of streptomycin-treated mice and untreated controls. We found that the microbiota in the ileum of untreated mice differed greatly from that of the cecum of the same mice, primarily among families of the phylum Firmicutes. Upon treatment with streptomycin, substantial changes in the microbial composition occurred, with a marked loss of population complexity. Characterization of the metabolic products of the microbiota, the SCFAs, showed that formate was present in the ileum but low or not detectable in the cecum while butyrate was present in the cecum but not the ileum. Treatment with streptomycin altered the SCFAs in the cecum, significantly decreasing the concentration of acetate, propionate, and butyrate. In this work, we also characterized the pathology of Salmonella infection in the ileum. Infection of streptomycin-treated mice with Salmonella was characterized by a significant increase in the relative and absolute levels of the pathogen and was associated with more severe ileal inflammation and pathology. Together these results provide a better understanding of the ileal environment in the mouse and the changes that occur upon streptomycin treatment.

Musical intervals in speech.

Throughout history and across cultures, humans have created music using pitch intervals that divide octaves into the 12 tones of the chromatic scale. Why these specific intervals in music are preferred, however, is not known. In the present study, we analyzed a database of individually spoken English vowel phones to examine the hypothesis that musical intervals arise from the relationships of the formants in speech spectra that determine the perceptions of distinct vowels. Expressed as ratios, the frequency relationships of the first two formants in vowel phones represent all 12 intervals of the chromatic scale. Were the formants to fall outside the ranges found in the human voice, their relationships would generate either a less complete or a more dilute representation of these specific intervals. These results imply that human preference for the intervals of the chromatic scale arises from experience with the way speech formants modulate laryngeal harmonics to create different phonemes.

Evaluation of two procedures to determine acid and neutral detergent fibers in ruminant feeds of the temperate region of Argentina.

The objective of this work was to compare the traditional Van Soest's procedure to analyze neutral detergent fibers (NDF) and acid detergent fibers (ADF) using filtering crucibles (VS) with a semiautomatic method which uses filter bags in an ANKOM Technology Corp. instrument (ANK). Nine ruminant feeds widely used in the temperate region of Argentina were analyzed: soybean meal expeller, alfalfa, pasture silage, ryegrass, corn silage, weeping lovegrass, tall wheatgrass, guinea grass, and barley grass. Four runs were done for each technique and feed. The comparison of ADF and NDF means by the means test for paired samples showed no significant differences between techniques (alpha = 0.01). The variability among runs was greater with the VS method than the ANK, both for NDF, standard deviation (SD) = 0.71 vs 0.39, and for ADF, SD = 0.83 vs 0.56, but the differences were not significant. The linear regressions were VS = 1.43 + 0.95 ANK; R2 = 0.99, and VS = 0.53 + 0.98 ANK; R2 = 0.99 for NDF and ADF, respectively, which indicated a strong linear relationship among the results of both procedures. It was concluded that the ANK procedure gave results comparable to those of the VS method when ruminant feeds from the temperate region of Argentina were analyzed.

The consequences of Conduct Disorder for males who develop schizophrenia: associations with criminality, aggressive behavior, substance use, and psychiatric services.

Men with schizophrenia are at increased risk, as compared to the general population, for criminal offending and to have displayed Conduct Disorder (CD) before age 15. The present study examined the consequences of CD among a sample of 248 men with schizophrenia or schizo-affective disorder, aged, on average, 39 years old. Participants were intensively assessed at discharge from the hospital and four times during the subsequent two-year period. CD was associated with criminality and substance misuse among first-degree male relatives and substance misuse among female relatives. In childhood and adolescence, CD was associated with poor academic performance, substance abuse, and physical abuse. In adulthood, the diagnosis of CD and each CD symptom were associated with increased non-violent and violent criminal offending, after adjusting for life-time diagnoses of substance misuse disorders. CD was not associated with homicide. CD was associated with life-time diagnoses of alcohol and drug abuse and/or dependence. During the 24 month follow-up period, CD and the number of CD symptoms were associated with aggressive behavior, controlling for life-time diagnoses of substance use disorders, substance misuse measured objectively and subjectively, medication compliance, and obligatory care. CD was associated with an earlier age at onset of schizophrenia and at first admission to hospital, and with length of time spent in hospital. During the two-year follow-up period, neither the diagnosis of CD nor the number of CD symptoms was associated with levels of positive and negative symptoms assessed five times, compliance with medication, substance use, or readmission. The results are interpreted to suggest that CD is a distinct co-morbid disorder that runs parallel to the course of schizophrenia.

Straightness as a cue for luminance edge interpretation.

In order to determine the reflectance of a surface, it is necessary to discount luminance changes produced by illumination variation, a process that requires the visual system to respond differently to luminance changes that are due to illumination and reflectance. It is known that various cues can be used in this process. By measuring the strength of lightness illusions, we find evidence that straightness is, used as a cue: When a boundary is straight rather than curved, it has a greater tendency to be discounted, as if it were an illumination edge. The strongest illusions occur when a boundary has high contrast and has multiple X-junctions that preserve a consistent contrast ratio.

Adelson's tile and snake illusions: a Helmholtzian type of simultaneous lightness contrast.

Adelson's tile, snake, and some other lightness illusions of the same type were measured with the Munsell neutral scale for twenty observers. It was shown that theories based on low-level luminance contrast processing could hardly explain these illusions. Neither can those based on luminance X-junctions. On the other hand, Helmholtz's idea, that simultaneous lightness contrast originates from an error in judgement of apparent illumination, has been elaborated so as to account for the tile and snake illusions as well as other demonstrations presented in this report.

Unusual reaction to fluorescein dye in patients with inflammatory eye disease.

PURPOSE: Ocular side effects attributable to intravenous fluorescein dye are not well characterized. The purpose of this report was to describe three patients with an unusual ocular reaction after the intravenous administration of fluorescein dye. METHODS: Retrospective review of the clinical and photographic records of three patients. RESULTS: Each patient had some type of preexisting ocular inflammatory disease. Each patient described the subacute onset of a unilateral burning sensation and tearing several minutes after the administration of intravenous fluorescein dye. Findings included a new onset of or a worsening of unilateral conjunctival chemosis and injection in all three patients and yellowish discoloration of the conjunctiva in two patients. In each patient, the noninflamed (fellow) eye did not develop any symptoms or show any visible reaction. The symptoms and findings resolved promptly in the affected eye without specific treatment or effect on vision. CONCLUSIONS: Ocular side effects of intravenous fluorescein dye can include transient symptomatic burning and tearing associated with conjunctival chemosis, injection, and yellowish discoloration. Eyes with active inflammatory diseases may be predisposed to this rare effect through an unclear mechanism.