Evidence for distinct genetic and environmental influences on fear acquisition and extinction.

BACKGROUND: Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. METHODS: In total, 1937 twins aged 22-25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. RESULTS: Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4-0.5). CONCLUSIONS: Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.

Introducing the Fear Learning and Anxiety Response (FLARe) app and web portal for the remote delivery of fear conditioning experiments.

Experimental paradigms measuring key psychological constructs can enhance our understanding of mechanisms underlying human psychological well-being and mental health. Delivering such paradigms remotely affords opportunities to reach larger, more representative samples than is typically possible with in-person research. The efficiency gained from remote delivery makes it easier to test replication of previously established effects in well-powered samples. There are several challenges to the successful development and delivery of remote experimental paradigms, including use of an appropriate delivery platform, identifying feasible outcome measures, and metrics of participant compliance. In this paper, we present FLARe (Fear Learning and Anxiety Response), open-source software in the form of a smartphone app and web portal for the creation and delivery of remote fear conditioning experiments. We describe the benefits and challenges associated with the creation of a remote delivery platform for fear conditioning, before presenting in detail the resultant software suite, and one instance of deploying this using the FLARe Research infrastructure. We provide examples of the application of FLARe to several research questions which illustrate the benefits of the remote approach to experiment delivery. The FLARe smartphone app and web portal are available for use by other researchers and have been designed to be user-friendly and intuitive. We hope that FLARe will be a useful tool for those interested in conducting well-powered fear conditioning studies to inform our understanding of the development and treatment of anxiety disorders.

The Ability of Family Physicians in the Caribbean to Promote Planetary Health Concepts and the Challenges of Implementing Changes in Practice

The global environment is rapidly changing and the subsequent effects on human health are devastating. Planetary Health is a field focused on characterizing the human health impacts of human-caused disruptions of Earth's natural systems. It has been determined that Family Physicians (FPs) are the best suited to advocate and raise awareness of Planetary Health. The purpose of this research is to assess FPs in the Caribbean, their knowledge of planetary health, their ability to implement planetary health concepts in their practice, and the challenges that may impede implementation.

Validating the use of a smartphone app for remote administration of a fear conditioning paradigm.

Fear conditioning models key processes related to the development, maintenance and treatment of anxiety disorders and is associated with group differences in anxiety. However, laboratory administration of tasks is time and cost intensive, precluding assessment in large samplesnecessary for the analysis of individual differences. This study introduces a newly developed smartphone app that delivers a fear conditioning paradigm remotely using a loud human scream as an aversive stimulus. Three groups of participants (total n = 152) took part in three studies involving a differential fear conditioning experiment to assess the reliability and validity of a smartphone administered fear conditioning paradigm. This comprised of fear acquisition, generalisation, extinction, and renewal phases during which online US-expectancy ratings were collected during every trial with evaluative ratings of negative affect at three time points. We show that smartphone app delivery of a fear conditioning paradigm results in a pattern of fear learning comparable to traditional laboratory delivery and is able to detect individual differences in performance that show comparable associations with anxiety to the prior group differences literature.

Challenges for the Travelling Donor: Variability Between Donor Workup and Donor Surgery in the Canadian Kidney Paired Exchange Program.

BACKGROUND: A primary obstacle to providing renal transplantation is limited access to donated kidneys. The living-donor pool for renal allografts was greatly expanded through implementation of a kidney paired donation program. Whereas some programs ship donor kidneys to the site of renal transplantation, others send the donor to the site of transplantation. Performing the nephrectomy and transplantation at the same location may optimize functional renal outcomes, but preferred surgical approaches may differ between surgical teams performing the donor workup and donor surgery. Our objective was to identify incongruence between the surgery planned by the team that performed the donor's workup, and the surgery that took place at the site of donation. METHODS: A retrospective chart review was performed between the site of preoperative surgical planning, and the site of surgery for kidney donors in the Canadian kidney paired donation program. RESULTS: Fifty-one donors were preoperatively prepared in any of six Canadian provinces, and then underwent surgery in a different province. The surgical procedure performed for 31% of the patients' nephrectomies differed from the procedure suggested by the surgical team who conducted the preoperative workup. Half of these differences were between left laparoscopic and left laparoscopic hand-assisted, but the remainder included more substantial changes of sides and/or laparoscopic versus open procedures. CONCLUSION: Optimal patient care is challenged in a kidney paired donation program that uses the "traveling donor" approach due to differing surgical techniques selected by the surgeon at the site of donor workup and the surgeon at the site of donation.

Attitudes of clinicians following large-scale pharmacogenomics implementation.

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring prescriptions, but clinicians do not agree on how to appropriately assign clinical responsibility for actionable results from a multiplexed panel.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.57.

Management of Complicated Ureteric Strictures After Renal Transplantation: Case Series of Pyelovesicostomy With Boari Flap.

Ureteric strictures are the most common urologic complication following renal transplantation. Different management options exist, ranging from temporizing drainage with ureteric stent or percutaneous nephrostomy tube to endoscopic interventions and open surgical repair. Although minimally invasive procedures are typically preferred, they often have a short duration of efficacy and multiple treatments are required. Open surgical repair allows for definitive management with minimal risk to the transplant. We review our experience with complicated ureteral strictures refractory to endoscopic management. We identified 10 renal transplant recipients who developed ureteric strictures that failed multiple endoscopic treatments. All 10 of these strictures were managed by means of pyelovesicostomy with the use of a Boari flap. The median time to ureteric stricture diagnosis was 2.5 months with a median of 4 endoscopic procedures before surgery. Median time from stricture diagnosis to surgical repair was 53 months. Overall success was 100%, with graft function being salvaged in all cases and no stricture recurrence after a mean follow-up of 18 months. We present a case series of complex ureteric strictures after renal transplantation managed by means of pyelovesicostomy with the use of Boari flap after failed endoscopic management. We demonstrate the safety and effectiveness of this approach of to treat complex ureteric strictures.

Novel B3GALTL mutations in classic Peters plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes.

Peters plus syndrome (PPS) is a rare autosomal-recessive disorder characterized by Peters anomaly of the eye, short stature, brachydactyly, dysmorphic facial features, developmental delay, and variable other systemic abnormalities. In this report, we describe screening of 64 patients affected with PPS, isolated Peters anomaly and PPS-like phenotypes. Mutations in the coding region of B3GALTL were identified in nine patients; six had a documented phenotype of classic PPS and the remaining three had a clinical diagnosis of PPS with incomplete clinical documentation. A total of nine different pathogenic alleles were identified. Five alleles are novel including one frameshift, c.168dupA, p.(Gly57Argfs*11), one nonsense, c.1234C>T, p.(Arg412*), two missense, c.1045G>A, p.(Asp349Asn) and c.1181G>A, p.(Gly394Glu), and one splicing, c.347+5G>T, mutations. Consistent with previous reports, the c.660+1G>A mutation was the most common mutation identified, seen in eight of the nine patients and accounting for 55% of pathogenic alleles in this study and 69% of all reported pathogenic alleles; while two patients were homozygous for this mutation, the majority had a second rare pathogenic allele. We also report the absence of B3GALTL mutations in 55 cases of PPS-like phenotypes or isolated Peters anomaly, further establishing the strong association of B3GALTL mutations with classic PPS only.

Inclusion of pediatric samples in an opt-out biorepository linking DNA to de-identified medical records: pediatric BioVU.

The Vanderbilt DNA repository, BioVU, links DNA from leftover clinical blood samples to de-identified electronic medical records (EMRs). After initiating adult sample collection, pediatric extension required consideration of ethical concerns specific to pediatrics and implementation of specialized DNA extraction methods. In the first year of pediatric sample collection, more than 11,000 samples from individuals younger than 18 years were included. We compared data from the pediatric BioVU cohort with those from the overall Vanderbilt University Medical Center pediatric population and found similar demographic characteristics; however, the BioVU cohort had higher rates of select diseases, medication exposures, and laboratory testing, demonstrating enriched representation of severe or chronic disease. The fact that the sample accumulation is not balanced may accelerate research in some cohorts while limiting the study of relatively benign conditions and the accrual of unaffected and unbiased control samples. BioVU represents a feasible model for pediatric DNA biobanking but involves both ethical and practical considerations specific to the pediatric population.

Haptic Classification of Facial Identity in 2D Displays: Configural versus Feature-Based Processing.

Participants learned through feedback to haptically classify the identity of upright versus inverted versus scrambled faces depicted in simple 2D raised-line displays. We investigated whether identity classification would make use of a configural face representation, as is evidenced for vision and 3D haptic facial displays. Upright and scrambled faces produced equivalent accuracy, and both were identified more accurately than inverted faces. The mean magnitude of the haptic inversion effect for 2D facial identity was a sizable 26 percent, indicating that the upright orientation was ¿privileged¿ in the haptic representations of facial identity in these 2D displays, as with other facial modalities. However, given the effect of scrambling, we conclude that configural processing was not employed; rather, only local information about the features was used, the features being treated as oriented objects within a body-centered frame of reference. The results indicate a fundamental difference between haptic identification of 2D facial depictions and 3D faces, paralleling a corresponding difference in recognition of nonface objects.

Laser-based volumetric flow visualization by digital color imaging of a spectrally coded volume.

We present the framework for volumetric laser-based flow visualization instrumentation using a spectrally coded volume to achieve three-component three-dimensional particle velocimetry. By delivering light from a frequency doubled Nd:YAG laser with an optical fiber, we exploit stimulated Raman scattering within the fiber to generate a continuum spanning the visible spectrum from 500 to 850 nm. We shape and disperse the continuum light to illuminate a measurement volume of 20 x 10 x 4 mm(3), in which light sheets of differing spectral properties overlap to form an unambiguous color variation along the depth direction. Using a digital color camera we obtain images of particle fields in this volume. We extract the full spatial distribution of particles with depth inferred from particle color. This paper provides a proof of principle of this instrument, examining the spatial distribution of a static field and a spray field of water droplets ejected by the nozzle of an airbrush.

Sequence-dependent conformational changes in DNA induced by polynuclear platinum complexes.

In this work, the B-->Z transition of poly(dG-dC).poly(dG-dC) and the B-->A transition of poly(dG).poly(dC) and of calf thymus (CT) DNA fragments modified by antitumor bifunctional polynuclear platinum complexes were investigated by circular dichroism (CD). The transition from the B- to Z-form of DNA was inducible with all three compounds studied, as indicated by an inversion of the B-form spectra. The B-->A transition in poly(dG).poly(dC) was induced easily by platinum complex binding alone, while the B-->A transition in CT DNA was induced by ethanol but inhibited by coordination of all polynuclear platinum compounds used here. It was shown that the compound [¿cis-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/c,c) was most effective at inhibiting the B-->A transition in CT DNA, and [¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6NH2)2¿] (NO3)4 (1,0,1/t,t,t) was least effective, while the effectiveness of [¿trans-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/t,t) fell between the two. This corresponded to the relative amounts of interstrand crosslinks in double-stranded DNA caused by each compound.