Feasibility and acceptability of a group music creativity intervention for adults with varying cognitive function.

Maintaining healthy cognitive functioning and delaying cognitive decline in cognitively intact and cognitive impaired adults are major research initiatives for addressing dementia disease burden. Music interventions are promising, non-pharmaceutical treatment options for preserving cognitive function and psychological health in older adults with varying levels of cognitive function. While passive, music interventions have attracted considerable attention in the abnormal cognitive aging literature, active, music interventions such as music creativity are less well-studied. Among 58 older adults with different levels of cognitive function (cognitively healthy to mild cognitive impairment), we examined the feasibility and acceptability of Project CHROMA, a Stage 1 clinical trial developed to assess the effects of a novel, music creativity curriculum on various health outcomes. Music intervention participation (93%), overall study retention (78%), and intervention satisfaction (100%) rates were comparable to other similarly designed clinical trials. Exploratory analyses using mixed-level modeling tested the efficacy of the intervention on cognitive and psychological outcomes. Compared to those in the control condition, participants in the music condition showed some improvements in cognitive functioning and socioemotional well-being. Findings suggest that a 6-week music creativity clinical trial with several multi-modal health assessments can be feasibly implemented within a sample of varying cognitive ability.

Dalbavancin vs standard of care for Staphylococcus aureus bacteraemia in patients unable to receive outpatient parenteral antimicrobial therapy.

BACKGROUND: This study compared dalbavancin with standard of care (SOC) for patients with Staphylococcus aureus bacteraemia (SAB) who were unable to receive outpatient parenteral antimicrobial therapy (OPAT). METHODS: This retrospective cohort compared re-admission rates related to the index infection between patients treated with dalbavancin or SOC for SAB. Patients aged ≥18 years seen by the infectious diseases consult service who had received at least one dose of dalbavancin or at least 1 week of SOC parenteral antibacterials as directed therapy for SAB at the time of discharge were included. The SOC group consisted of patients transferred from the main hospital to one of the post-acute care facilities to complete parenteral antibacterials. The primary outcome was re-admission rate within 30 days of completion of therapy. Secondary outcomes included re-admission rate within 90 days of completion of therapy and adherence to the antibacterial regimen. RESULTS: Twenty-seven patients received dalbavancin and 27 patients received SOC. Baseline demographics were comparable between groups, although more patients in the SOC group had indwelling prostheses or hardware (4% vs 22%). The majority of SAB was caused by methicillin-susceptible S. aureus (56% vs 59%). Re-admission rates for the dalbavancin group were similar to those for the SOC group within 30 days (15% vs 22%; P=0.484) and 90 days (19% vs 22%; P=0.735) of completion of therapy. Adherence to the antibacterial regimen was significantly higher among patients treated with dalbavancin compared with SOC (85% vs 44%; P<0.001). CONCLUSIONS: Dalbavancin offers similar clinical outcomes to SOC for patients with SAB who are unable to receive OPAT.

Assessment of COVID-19 outbreaks in long-term care facilities.

BACKGROUND: The B.1.167.2 (Delta) variant quickly became the predominant circulating SARS-CoV-2 strain in the USA during summer 2021. Missouri identified a high number of outbreaks in long-term care facilities (LTCFs) across the state with low vaccination rates among LTCF staff members and poor adherence to mitigation measures within local communities. AIM: To describe COVID-19 outbreaks that occurred in Missouri LTCFs impacting staff and residents during the surge of the Delta variant. METHODS: Outbreaks of COVID-19 in 178 LTCFs were identified by the Missouri Department of Health and Senior Services. Case data from LTCFs with the highest burden of disease were analysed to assess disease transmission, vaccination status, and outcomes among residents and staff. Additional investigational measures included onsite visits to facilities with recent COVID-19 outbreaks in communities with substantial transmission to assess mitigation measures. FINDINGS: During April 22nd to July 29th, 2021, 159 COVID-19 cases among 72 staff members and 87 residents were identified in 10 LTCFs. More than 74.7% of resident cases were vaccinated compared to 23.6% of staff cases. Vaccinated residents had a lower proportion of hospitalizations and deaths reported compared to unvaccinated residents. Data analysis and contact-tracing efforts from a sample of the facilities suggest that staff members were likely a major factor in introducing SARS-CoV-2 virus into the facilities. Adherence to COVID-19 mitigation measures varied at the visited facilities. CONCLUSION: Data showed that vaccination rates varied between staff cases and resident cases in facilities with high-burden outbreaks. Differences were identified in mitigation practices in at least two facilities.

Psychiatric diagnostic dilemmas among people with intellectual and developmental disabilities.

BACKGROUND: Research regarding the accuracy of co-morbid psychiatric diagnoses in individuals with intellectual and developmental disabilities (IDD) is sparse. Yet correct diagnostic assignment is vital so that effective and appropriate treatment can be implemented, especially for the large numbers of individuals requiring expensive and restrictive behavioural health crisis services. METHOD: A retrospective review of de-identified data from multidisciplinary specialty team assessments completed for 50 individuals with ID (IntellectualDisability) with and without ASD and unresolved behavioural health challenges was conducted. The accuracy and reliability of the psychiatric diagnoses upon referral were compared with the diagnoses after the comprehensive team evaluation, and within-individual diagnostic agreement was calculated. The agreement between the Mood and Anxiety Semi-Structured interview tool (MASS) and the full team evaluation was also calculated. The influence of demographic and clinical characteristics on diagnostic agreement was explored. RESULTS: The most common chief complaints upon referral were aggression to others and self-injurious behaviour. Individuals were taking a median of six medications (interquartile range: 5 to 7); 80% were taking an antipsychotic medication. The most common medical conditions were constipation (70%) and gastroesophageal reflux disease (52%). Measures of interrater reliability of the referral diagnoses with the team assessment were below 0.5 (kappa range: -0.04 to 0.39), with the exception of ruling out dementia (kappa = 0.85). The interrater reliability estimates for the MASS evaluations for depression and anxiety were higher (kappa = 0.69 and 0.64) and reflected higher sensitivity and PPV. The odds of any referral diagnosis being confirmed by team evaluation were low: 0.25 (range: 0 to 0.67). The level of diagnostic agreement for each patient was not significantly attributable to demographic or clinical characteristics, although effect sizes indicate a possible positive relationship to age and the number of prescribed psychotropic medications at referral. CONCLUSION: Individuals in the current study had serious psychiatric and behavioural problems despite psychiatric care in their communities. The majority of psychiatric diagnoses provided upon referral were not supported by the multidisciplinary specialty team's assessment. In addition to possible diagnostic inaccuracy, the group in the study suffered from multiple medical co-morbidities and were exposed to polypharmacy. Results emphasise the importance of multidisciplinary evaluation by clinicians with expertise in neurodevelopmental disabilities when people with ID with and without ASD have complex behavioural health needs that are unresponsive to usual care. In addition, based on agreement with the full team evaluation, the MASS shows promise as an assessment tool, especially with regards to identifying anxiety and depression.

Music to My Ears: Neural modularity and flexibility differ in response to real-world music stimuli.

Music listening involves many simultaneous neural operations, including auditory processing, working memory, temporal sequencing, pitch tracking, anticipation, reward, and emotion, and thus, a full investigation of music cognition would benefit from whole-brain analyses. Here, we quantify whole-brain activity while participants listen to a variety of music and speech auditory pieces using two network measures that are grounded in complex systems theory: modularity, which measures the degree to which brain regions are interacting in communities, and flexibility, which measures the rate that brain regions switch the communities to which they belong. In a music and brain connectivity study that is part of a larger clinical investigation into music listening and stroke recovery at Houston Methodist Hospital's Center for Performing Arts Medicine, functional magnetic resonance imaging (fMRI) was performed on healthy participants while they listened to self-selected music to which they felt a positive emotional attachment, as well as culturally familiar music (J.S. Bach), culturally unfamiliar music (Gagaku court music of medieval Japan), and several excerpts of speech. There was a marked contrast among the whole-brain networks during the different types of auditory pieces, in particular for the unfamiliar music. During the self-selected and Bach tracks, participants' whole-brain networks exhibited modular organization that was significantly coordinated with the network flexibility. Meanwhile, when the Gagaku music was played, this relationship between brain network modularity and flexibility largely disappeared. In addition, while the auditory cortex's flexibility during the self-selected piece was equivalent to that during Bach, it was more flexible during Gagaku. The results suggest that the modularity and flexibility measures of whole-brain activity have the potential to lead to new insights into the complex neural function that occurs during music perception of real-world songs.

Experimental Manipulation of Corticosterone Does Not Affect Venom Composition or Functional Activity in Free-Ranging Rattlesnakes.

AbstractVenom is an integral feeding trait in many animal species. Although venom often varies ontogenetically, little is known about the proximate physiological mediators of venom variation within individuals. The glucocorticoid hormone corticosterone (CORT) can alter the transcription and activation of proteins, including homologues of snake venom components such as snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2). CORT is endogenously produced by snakes, varies seasonally and also in response to stress, and is a candidate endogenous mediator of changes in venom composition and functional activity. Here, we tested the hypothesis that CORT induces changes in snake venom by sampling the venom of wild adult rattlesnakes before and after they were treated with either empty (control) or CORT-filled (treatment) Silastic implants. We measured longitudinal changes in whole-venom composition, whole-venom total protein content, and enzymatic activity of SVMP and PLA2 components of venom. We also assessed the within-individual repeatability of venom components. Despite successfully elevating plasma CORT in the treatment group, we found no effect of CORT treatment or average plasma CORT level on any venom variables measured. Except for total protein content, venom components were highly repeatable within individuals ([Formula: see text]). Our results indicate that the effects of CORT, a hormone commonly associated with stress and metabolic functions, in adult rattlesnake venom are negligible. Our findings bode well for venom researchers and biomedical applications that rely on the consistency of venoms produced from potentially stressed individuals and provide an experimental framework for future studies of proximate mediators of venom variation across an individual's life span.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Impact of bilateral ureteral reimplantation at the time of complete primary repair of bladder exstrophy on reflux rates, renogram abnormalities and bladder capacity.

INTRODUCTION: Bilateral ureteral reimplantation at the time of the complete primary repair of bladder exstrophy (BUR-CPRE) has been proposed and has demonstrated favorable outcomes in the past. However, the potential benefits, including prevention of vesicoureteral reflux (VUR) and renal scarring must be tempered with any risks of reimplantation, persistent VUR, and the potential for overtreatment. We aimed to determine the impact of BUR-CPRE on reflux rates, renogram findings and bladder capacity. METHODS: An IRB approved registry of children treated for bladder exstrophy epispadias complex (BEEC) during a long-term international collaboration hosted in a region with high prevalence of BEEC was queried. Children undergoing primary CPRE for bladder exstrophy (BE) were identified. Surgical procedure and outcome measures nuclear medicine dimercaptosuccinic acid (DMSA) scintigraphy scans, voiding cystourethrogram (VCUG), and urodynamic study (UDS) were assessed for presence and degree of VUR, renogram abnormalities, and bladder capacity. RESULTS: A total cohort of 147 patients with BEEC was queried; 52 children (37 males, 71%) underwent primary CPRE for BE between 2009 and 2019 at median age of 1.1 years (IQR 0.6-1.9 years) with median follow up 4.4 years (IQR 2.4-6.4 years). BUR-CPRE was performed in 22/52 (42%). After BUR-CPRE, children were less likely to have VUR (any VUR present in 9 of 20 with imaging (45%) compared to 23 of 26 with imaging (82%) in the CPRE alone group (p = 0.007)). VUR in the BUR-CPRE group tended to be unilateral and lower grade in comparison to the CPRE alone group. DMSA abnormalities were less common in the BUR-CPRE group (4/19 (21%) vs.12/27 (44%)), although the difference did not reach statistical significance (p = 0.1). At 4 years follow-up, the BUR-CPRE group had a larger bladder capacity (p = 0.016). DISCUSSION: After BUR-CPRE, children had a lower rate of VUR, and when present, VUR was more often unilateral and lower grade compared to the CPRE alone group. Fewer numbers of children in the BUR-CPRE group depicted DMSA abnormalities. No children developed obstruction after BUR-CPRE and none have undergone repeat reimplantation. We documented a larger bladder capacity at the time of maximum follow-up available (4 years)-but further data are needed to confirm this observation. CONCLUSION: BUR-CPRE decreases the incidence and severity of VUR after CPRE, but the clinical significance of this remains unclear. We are encouraged by these initial results, but since BUR-CPRE does not uniformly eliminate VUR, we continue to proceed carefully in the well selected patient.

Similarity of individual functional brain connectivity patterns formed by music listening quantified with a data-driven approach.

INTRODUCTION: This study aims to explore the similarities in functional connectivity (FC) patterns in individuals when listening to different music genres and, in comparison, to the spoken word, using a novel data-driven approach. Our model and findings can potentially be utilized for evaluating the neurological effects of therapeutic music interventions. MATERIALS AND METHODS: Twelve healthy volunteers listened to seven different sound tracks while undergoing functional magnetic resonance imaging (fMRI) scans: music of the volunteer's choice with positive emotional attachment, two selections of unfamiliar classical music, one classical piece repeated with visual guidance and three spoken language tracks. FC network graphs were created, and selected graph properties were evaluated toward their commonalities across sound tracks. For comparison, FC patterns represented by the graph adjacency matrices were directly compared for high and low BOLD activation during listening. RESULTS: Graph properties averaged across subjects showed similar values for the same sound track compared to different sound tracks (p < 0.003). For high BOLD activation involving most areas in the auditory cortex, FC patterns for the same sound track correlated highly (0.74 ± 0.11), whereas FC patterns for different sound tracks did not (0.09 ± 0.07; p < 6e-5). For low BOLD activation involving additional brain regions, correlation of FC patterns for the sound tracks was still higher (0.43 ± 0.07) than for different sound tracks (0.09 ± 0.05; p < 8e-6). CONCLUSION: Similar music creates similar functional activation and connectivity patterns in the brain of healthy individuals as does listening to the spoken word. Direct comparison of FC patterns yielded higher correlations than indirect comparisons of graph properties derived from corresponding FC networks.

An Exploratory Pilot Study of Brain Activation and Functional Connectivity Induced by the "Goldberg" Variations 276 years after their Commission.

Around 1741, composer Johann Sebastian Bach published a long and complicated keyboard piece, calling it Aria with diverse variations for a harpsichord with two manuals. It was the capstone of a publication project called German Clavier-Übung (Keyboard Practice) where Bach wanted to show what was possible at the keyboard in terms of technical development, virtuosic finesse and compositional sophistication. The music is meticulously patterned, beginning with a highly ornamented Aria, the bass line of which fuels the 30 variations that follow. The piece is clearly divided into two parts with the second half beginning with an overture with a fanfare opening, in variation 16. The piece ends as it begins, with the return of the Aria. Here, we present an investigation into activation and connectivity in the brain of a pianist, who listened to her own recording of the "Goldberg" variation while undergoing a fMRI examination. Similarity of brain connectivity is quantified and compared with the subjective scores provided by the subject.

Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module for youth with Type 2 diabetes: reliability and validity.

AIM: To test the measurement properties of the revised and updated Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module originally developed in Type 1 diabetes in youth with Type 2 diabetes. METHODS: The PedsQL 3.2 Diabetes Module and PedsQL Generic Core Scales were administered in a field test study to 100 young people aged 9-25 years with Type 2 diabetes. Factor analysis was conducted to determine the factor structure of the items. RESULTS: The 15-item Diabetes Symptoms Summary Score and 12-item Type 2-specific Diabetes Management Summary Score were empirically derived through factor analysis. The Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores showed acceptable to excellent reliability across the age groups tested (α = 0.85-0.94). The Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores evidenced construct validity through large effect size correlations with the Generic Core Scales Total Scale Score (r = 0.67 and 0.57, respectively). HbA1c was correlated with the Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores (r = -0.13 and -0.22). Minimal clinically important difference (MCID) scores were 5.91 and 7.39 for the Diabetes Symptoms and Type 2-specific Diabetes Management Summary Scores. CONCLUSIONS: The PedsQL 3.2 Diabetes Module Diabetes Symptoms Summary Score and Type 2-specific Diabetes Management Summary Score exhibited satisfactory measurement properties for use as youth self-reported diabetes symptoms and diabetes management outcomes for clinical research and clinical practice for young people with Type 2 diabetes.

Back to the future: The Cecil-Culp technique for salvage penile reconstructive procedures.

INTRODUCTION: Re-operative penile reconstruction is challenging and requires tension-free skin closure. The repair popularized by Cecil and Culp in the 1940s, using the scrotum to provide a temporary vascularized bed for complex hypospadias repairs, fell out of favor due to temporal trends towards single-stage repairs and concern for utilizing hair-bearing skin on the penile shaft. OBJECTIVE: It was hypothesized that a modified Cecil-Culp (CC) concept of penile scrotalization, leaving the penis attached to the scrotum for 1 year rather than 6 weeks as originally described, improves outcomes with this reconstruction for ventral skin deficiency or poor vascular support. METHODS: Institutional Review Board-approved registries were reviewed to identify patients who underwent a CC repair during 1987-2016 at two institutions. Cecil-Culp technique was utilized in multi-stage hypospadias complication repairs or for insufficient ventral penile shaft skin coverage. Anatomic abnormality, number and type of prior surgeries, and complications before and after CC were recorded. RESULTS: Thirty-nine patients underwent CC: 23 failed hypospadias repairs, three hypospadias after bladder exstrophy, 10 penile curvature following circumcision, and three with skin loss from trauma. Mean age at CC was 61.8 months (hypospadias), and 59.8 months (non-hypospadias). Hypospadias patients underwent a mean of 3.6 surgeries (range 1-9) prior to CC. Four of the 39 patients (10.3%) had perioperative complications after CC, including scrotal abscess, skin infections, and difficulty removing the urethral stent. Eight of 37 (21.6%) patients had longer-term complications related to their hypospadias repair, including fistulae, diverticula, dehiscence, and stricture. Mean time from CC placement to release was 345 and 473 days for hypospadias and non-hypospadias cases, respectively. There was no apparent scrotal skin transferred to the penile shaft at the final take-down. Mean follow-up was 22.3 months. DISCUSSION: Embedding the penis into the scrotum for added vascularity and ventral skin coverage has been used effectively in cases of the most tenacious fistulas and for significant skin loss and trauma. Limitations of this study were its retrospective approach at two institutions over an extended period of time by multiple surgeons, so patient selection and procedure may have varied. CONCLUSIONS: Modification of CC repair by delaying 9-12 months before CC take-down enhanced the benefits of a robust vascular bed for wound healing, and helped to avoid transfer of hair-bearing scrotal skin to the penile shaft. The CC technique is an important tool for penile reconstructive surgery of complex hypospadias repairs with inadequate skin, and for traumatic injuries.

Heritable plant phenotypes track light and herbivory levels at fine spatial scales.

Organismal phenotypes often co-vary with environmental variables across broad geographic ranges. Less is known about the extent to which phenotypes match local conditions when multiple biotic and abiotic stressors vary at fine spatial scales. Bittercress (Brassicaceae: Cardamine cordifolia), a perennial forb, grows across a microgeographic mosaic of two contrasting herbivory regimes: high herbivory in meadows (sun habitats) and low herbivory in deeply shaded forest understories (shade habitats). We tested for local phenotypic differentiation in plant size, leaf morphology, and anti-herbivore defense (realized resistance and defensive chemicals, i.e., glucosinolates) across this habitat mosaic through reciprocal transplant-common garden experiments with clonally propagated rhizomes. We found habitat-specific divergence in morphological and defensive phenotypes that manifested as contrasting responses to growth in shade common gardens: weak petiole elongation and attenuated defenses in populations from shade habitats, and strong petiole elongation and elevated defenses in populations from sun habitats. These divergent phenotypes are generally consistent with reciprocal local adaptation: plants from shade habitats that naturally experience low herbivory show reduced investment in defense and an attenuated shade avoidance response, owing to its ineffectiveness within forest understories. By contrast, plants from sun habitats with high herbivory show shade-induced elongation, but no evidence of attenuated defenses canonically associated with elongation in shade-intolerant plant species. Finally, we observed differences in flowering phenology between habitat types that could potentially contribute to inter-habitat divergence by reducing gene flow. This study illuminates how clonally heritable plant phenotypes track a fine-grained mosaic of herbivore pressure and light availability in a native plant.

Establishment and characterization of a canine soft tissue sarcoma patient-derived xenograft model.

Spontaneously occurring soft tissue sarcoma (STS) is relatively common in canine cancer patients. Because of the similarities to human disease, canine STSs are a valuable and readily available resource for the study of new therapeutics. In this study, a canine patient-derived xenograft (PDX) model, CDX-STS2, was established. The CDX-STS2 model was engrafted and expanded for systemic administration studies with chemotherapeutic agents commonly used to treat STS, including doxorubicin, docetaxel and gemcitabine. Immunohistochemistry for drug-specific biomarkers and tumour growth measurement revealed tumour sensitivity to doxorubicin and docetaxel, whereas gemcitabine had no effect on tumour growth. Although many human PDX tumour models have been established, relatively few canine PDX models have been reported to date. CDX-STS2 represents a new STS PDX research model of canine origin that will be useful in bridging preclinical research with clinical studies of STS in pet dogs.

Longitudinal quality of life improvement in underserved rural youth with obesity.

OBJECTIVE: ACT! (Actively Changing Together) is a family- and community-based intervention targeting youth with obesity. The objective of this study was to establish the longitudinal impact on Health-Related Quality of Life (HRQoL) as well as the relationship with anthropometric and demographic factors. METHODS: Youth (n = 75) aged 8-14 years meeting criteria for overweight or obesity were referred to the programme. Twelve, 90-min classes in English and Spanish were held at the YMCA. Demographics and anthropometrics were assessed, as well as HRQoL that was measured with the child-reported Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scale. Data was collected at three follow-up points after completion of the intervention: initial follow-up (n = 65), 6 (n = 41) and 12 months (n = 25). Analysis included paired dependent t-tests between baseline and follow-up, and Pearson's correlations on HRQoL, anthropometric and demographic data. RESULTS: PedsQL scores significantly improved from baseline to all follow-up timepoints (initial follow-up immediately following the intervention, and 6 and 12 months post intervention). Over time, body mass index Z-Score and per cent body fat displayed various points of significance and strengthening correlations. CONCLUSIONS: Longitudinal improvements in HRQoL were sustained up to 12 months following a family- and community-based intervention in this underserved population. Anthropometric measures continuously correlated with and contributed to HRQoL outcomes.

Long-term behavioral impairment following acute embryonic ethanol exposure in zebrafish.

BACKGROUND: Developmental exposure to ethanol has long been known to cause persisting neurobehavioral impairment. However, the neural and behavioral mechanisms underlying these deficits and the importance of exposure timing are not well-characterized. Given the importance of timing and sequence in neurodevelopment it would be expected that alcohol intoxication at different developmental periods would result in distinct neurobehavioral consequences. METHODS: Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or 24-27 h post-fertilization (hpf) then reared to adolescence and evaluated on several behavioral endpoints. Habituation to a repeated environmental stimulus and overall sensorimotor function were assessed using a tap startle test; measurements of anxiety and exploration behavior were made following introduction to a novel tank; and spatial discrimination learning was assessed using aversive control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also scored (i.e. craniofacial malformations, including eye diameter and midbrain-hindbrain boundary morphology). RESULTS: Ethanol treated fish were more active both at baseline and following a tap stimulus compared to the control fish and were hyperactive when placed in a novel tank. These effects were more prominent following exposure at 24-27 hpf than with the earlier exposure window, for both dose groups. Increases in physical malformation were only present in the 3% ethanol group; all malformed fish were excluded from behavioral testing. DISCUSSION: These results suggest specific domains of behavior are affected following ethanol exposure, with some but not all of the tests revealing significant impairment. The behavioral phenotypes following distinct exposure windows described here can be used to help link cellular and molecular mechanisms of developmental ethanol exposure to functional neurobehavioral effects.

Graph theoretical connectivity analysis of the human brain while listening to music with emotional attachment: feasibility study.

Benefits of listening to music with emotional attachment while recovering from a cerebral ischemic event have been reported. To develop a better understanding of the effects of music listening on the human brain, an algorithm for the graph-theoretical analysis of functional magnetic resonance imaging (fMRI) data was developed. From BOLD data of two paradigms (block-design, first piece: music without emotional attachment, additional visual guidance by a moving cursor in the score sheet; second piece: music with emotional attachment), network graphs were constructed with correlations between signal time courses as edge weights. Functional subunits in these graphs were identified with the MCODE clustering algorithm and mapped back into anatomical space using AFNI. Emotional centers including the right amygdala and bilateral insula were activated by the second piece (emotional attachment) but not by the first piece. Network clustering analysis revealed two separate networks of small-world property corresponding to task-oriented and resting state conditions, respectively. Functional subunits with highest interactions were bilateral precuneus for the first piece and left middle frontal gyrus and right amygdala, bilateral insula, left middle temporal gyrus for the second piece. Our results indicate that fMRI in connection with graph theoretical network analysis is capable of identifying and differentiating functional subunits in the human brain when listening to music with and without emotional attachment.

Genome-wide association study of shared components of reading disability and language impairment.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Enhanced local processing of dynamic visual information in autism: evidence from speed discrimination.

An important issue for understanding visual perception in autism concerns whether individuals with this neurodevelopmental disorder possess an advantage in processing local visual information, and if so, what is the nature of this advantage. Perception of movement speed is a visual process that relies on computation of local spatiotemporal signals but requires the comparison of information from more than a single spatial location or temporal point. This study examined speed discrimination in adolescents (ages 13-18 years old) with autism spectrum disorders (ASD). Compared to healthy controls (n=17), individuals with ASD (n=19) showed similarly precise speed discrimination when two comparison motion stimuli (random dot patterns) were presented closely in time (0.5s). With a longer temporal interval (3s) between the motion stimuli, individuals with ASD outperformed healthy controls on speed discrimination. On a second task--global motion perception--in which individuals were asked to detect coherent motion, individuals with ASD exhibited slightly degraded performance levels. The observed temporally selective enhancement in speed discrimination indicates that a local processing advantage in autism develops over a longer temporal range and is not limited to the spatial domain. These results suggest a dynamic perceptual mechanism for understanding, and therapeutically addressing, atypical visual processing in this neurodevelopmental disorder.

Living Liquid: Design and Evaluation of an Exploratory Visualization Tool for Museum Visitors.

Interactive visualizations can allow science museum visitors to explore new worlds by seeing and interacting with scientific data. However, designing interactive visualizations for informal learning environments, such as museums, presents several challenges. First, visualizations must engage visitors on a personal level. Second, visitors often lack the background to interpret visualizations of scientific data. Third, visitors have very limited time at individual exhibits in museums. This paper examines these design considerations through the iterative development and evaluation of an interactive exhibit as a visualization tool that gives museumgoers access to scientific data generated and used by researchers. The exhibit prototype, Living Liquid, encourages visitors to ask and answer their own questions while exploring the time-varying global distribution of simulated marine microbes using a touchscreen interface. Iterative development proceeded through three rounds of formative evaluations using think-aloud protocols and interviews, each round informing a key visualization design decision: (1) what to visualize to initiate inquiry, (2) how to link data at the microscopic scale to global patterns, and (3) how to include additional data that allows visitors to pursue their own questions. Data from visitor evaluations suggests that, when designing visualizations for public audiences, one should (1) avoid distracting visitors from data that they should explore, (2) incorporate background information into the visualization, (3) favor understandability over scientific accuracy, and (4) layer data accessibility to structure inquiry. Lessons learned from this case study add to our growing understanding of how to use visualizations to actively engage learners with scientific data.