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Despite the fact that direct-to-consumer (DTC) genetic ancestry testing (GAT) has been available for two decades, there is a lack of evidence-based guidance for clinicians who may work with patients who raise the topic of DTC-GAT. Although DTC-GAT accounts for the majority of the DTC genetic testing marketplace, it has received less attention than health-related testing from scientific and clinical communities. Importantly, however, from our personal experience, patients have been raising the topic of DTC-GAT in clinical encounters, including psychotherapy sessions. In this viewpoint, we present two cases of patients seen by two of the authors to raise awareness of this issue. We describe the implications of DTC-GAT for patients and clinicians, offer recommendations, and suggest future directions.

An ever-increasing array of design visualisation tools are available to designers. As such, design education is constantly challenged to keep up with these trends so that students are best equipped for entering industrial practice. This paper reports a study into the use of digital sketching, a relatively new digital visualisation tool. The study aims to identify thematic differences in how students and practitioners perceive digital sketching. These are given in terms of the tool's characteristics, and how these characteristics guide its application in early stages of the design process. Data on perceptions is captured using design diaries and semistructured interviews. Results show key differences in the way that practitioners perceive the intent of visualisation. Practitioners focus on iterating towards a solution during the design process. Students are much more focused on the task of creating visualisations. This reveals an underlying contradiction in the way tools are perceived between creating visualisations to gain expertise or skill, versus creating them to advance the design process. The insights help improve our understanding of how the different characteristics of digital sketching inform its use. We reflect on how we educate students with respect to selecting and using digital sketching. We conclude with implications for education of digital sketching, as well as other emerging digital visualisation tools.

Event-related potentials (ERPs) are noninvasive measures of human brain activity that index a range of sensory, cognitive, affective, and motor processes. Despite their broad application across basic and clinical research, there is little standardization of ERP paradigms and analysis protocols across studies. To address this, we created ERP CORE (Compendium of Open Resources and Experiments), a set of optimized paradigms, experiment control scripts, data processing pipelines, and sample data (N = 40 neurotypical young adults) for seven widely used ERP components: N170, mismatch negativity (MMN), N2pc, N400, P3, lateralized readiness potential (LRP), and error-related negativity (ERN). This resource makes it possible for researchers to 1) employ standardized ERP paradigms in their research, 2) apply carefully designed analysis pipelines and use a priori selected parameters for data processing, 3) rigorously assess the quality of their data, and 4) test new analytic techniques with standardized data from a wide range of paradigms.

Cognitive impairment is a core feature of schizophrenia and a strong predictor of psychosocial disability. Auditory-based targeted cognitive training (TCT) aims to enhance verbal learning and other domains of cognitive functioning through "bottom-up" tuning of the neural systems underlying early auditory information processing (EAIP). Although TCT has demonstrated efficacy at the group level, individual response to TCT varies considerably, with nearly half of patients showing little-to-no benefit. EEG measures of EAIP, mismatch negativity (MMN) and P3a, are sensitive to the neural systems engaged by TCT exercises and might therefore predict clinical outcomes after a full course of treatment. This study aimed to determine whether initial malleability of MMN and P3a to 1-h of auditory-based TCT predicts improvements in verbal learning and clinical symptom reduction following a full (30-h) course of TCT. Treatment refractory patients diagnosed with schizophrenia were randomly assigned to receive treatment-as-usual (TAU; n = 22) or TAU augmented with TCT (n = 23). Results indicated that malleability (i.e., change from baseline after the initial 1-h dose of TCT) of MMN and P3a predicted improvements in verbal learning as well as decreases in the severity of positive symptoms. Examination of MMN and P3a malleability in patients after their first dose of TCT can be used to predict clinical response to a full course of treatment and shows promise for future biomarker-informed treatment assignment.

Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy.

The first multi-year contributions from organic functional groups to the Arctic submicron aerosol are documented using 126 weekly-integrated samples collected from April 2012 to October 2014 at the Alert Observatory (82.45° N, 62.51° W). Results from the particle transport model FLEXPART, linear regressions among the organic and inorganic components and positive matrix factorization (PMF) enable associations of organic aerosol components with source types and regions. Lower organic mass (OM) concentrations but higher ratios of OM to non-sea-salt sulfate mass concentrations (nss-SO4Combining double low line) accompany smaller particles during the summer (JJA). Conversely, higher OM but lower OM ĝ• nss-SO4Combining double low line accompany larger particles during winter-spring. OM ranges from 7 to 460 ng mĝ'3, and the study average is 129 ng mĝ'3. The monthly maximum in OM occurs during May, 1 month after the peak in nss-SO4Combining double low line and 2 months after that of elemental carbon (EC). Winter (DJF), spring (MAM), summer and fall (SON) values of OM ĝ• nss-SO4Combining double low line are 26, 28, 107 and 39 %, respectively, and overall about 40 % of the weekly variability in the OM is associated with nss-SO4Combining double low line. Respective study-Averaged concentrations of alkane, alcohol, acid, amine and carbonyl groups are 57, 24, 23, 15 and 11 ng mĝ'3, representing 42, 22, 18, 14 and 5 % of the OM, respectively. Carbonyl groups, detected mostly during spring, may have a connection with snow chemistry. The seasonally highest O ĝ• C occurs during winter (0.85) and the lowest O ĝ• C is during spring (0.51); increases in O ĝ• C are largely due to increases in alcohol groups. During winter, more than 50 % of the alcohol groups are associated with primary marine emissions, consistent with Shaw et al. (2010) and Frossard et al. (2011). A secondary marine connection, rather than a primary source, is suggested for the highest and most persistent O ĝ• C observed during the coolest and cleanest summer (2013), when alcohol and acid groups made up 63 % of the OM. A secondary marine source may be a general feature of the summer OM, but higher contributions from alkane groups to OM during the warmer summers of 2012 (53 %) and 2014 (50 %) were likely due to increased contributions from combustion sources. Evidence for significant contributions from biomass burning (BB) was present in 4 % of the weeks. During the dark months (NDJF), 29, 28 and 14 % of the nss-SO4Combining double low line, EC and OM were associated with transport times over the gas flaring region of northern Russia and other parts of Eurasia. During spring, those percentages dropped to 11 % for each of nss-SO4Combining double low line and EC values, respectively, and there is no association of OM. Large percentages of the Arctic haze characterized at Alert likely have origins farther than 10 days of transport time and may be from outside of the Eurasian region. Possible sources of unusually high nss-SO4Combining double low line and OM during September-October 2014 are volcanic emissions or the Smoking Hills' area of the Northwest Territories, Canada.

ObjectivesHIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants.MethodsNear-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naïve individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7.5 years. Subtypes were inferred by Los Alamos Recombinant Identification Program (RIP) 3.0 and compared with Sanger/REGA and MiSeq/RIP. 'Nonrecombinants' and 'recombinants' infections were compared in terms of pretherapy viral load, CD4 cell count, posttherapy time to virologic suppression, virologic rebound, first CD4 rise above baseline and sustained CD4 recovery.ResultsPrevalence of intersubtype recombinants varied depending on the genomic region examined: gag (15%), prrt (11%), int (8%), vif (10%), vpr (2%), vpu (9%), GP120 (8%), GP41 (18%), and nef (4%). Of the 200 patients with near-full-genome data, prevalence of intersubtype recombination was 46%; the most frequently observed recombinant was A1-D (25%). Sanger/REGA and MiSeq/RIP yielded generally consistent results. Phylogenetic tree revealed most recombinants did not share common ancestors. No temporal trend was observed (all P > 0.1). Subsequent subtype switches were detected in 27 of 143 (19%) study participants with follow-up sequences. Nonrecombinant versus recombinants infections were not significantly different in any pre nor posttherapy clinical correlates examined (all P > 0.2).ConclusionIntersubtype recombination was highly prevalent (46%) in Uganda if the entire HIV genome was considered, but was neither associated with clinical correlates nor therapy outcomes.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000.

People living with HIV/AIDS (PHA) often concurrently cope with mental health disorders that may greatly influence HIV and other health-related outcomes. The objective of this study was to examine the prevalence and correlates of self-reported mental health disorder diagnosis among a cohort of harder-to-reach HIV-positive individuals in British Columbia, Canada. Between 2007 and 2010, 1000 PHA who had initiated ART were enrolled in the Longitudinal Investigation into Supportive and Ancillary health services (LISA) study. Socio-demographic, behavioral, health-care utilization and psychosocial information was collected through interviewer-led questionnaires and linked to longitudinal clinical variables through the provincial Drug Treatment Program at the BC Centre for Excellence in HIV/AIDS. We identified the prevalence of all-type and specific mental health disorders among this population. Of the 916 participants included in this analysis, 494 (54%) reported ever having a mental health disorder diagnosis. Mood (85%) and anxiety (65%) disorders were the two most frequently reported mental health conditions. Self-reported all-type mental health disorder was independently associated with decreased overall functioning (adjusted odds ratio [AOR] = 0.90, 95% confidence interval [CI] = 0.83-0.98) and life satisfaction (AOR = 0.81, 95% CI = 0.74-0.89), and having higher stigma score (AOR = 1.11, 95%CI = 1.02-1.21). Participants reporting any mental health disorder were more likely to report a history of sexual assault (AOR = 2.45, 95% CI = 1.75-3.43) and to have used case management services (AOR = 1.63, 95%CI = 1.17-2.27). Our findings uncovered a high burden of mental health disorders among harder-to-reach PHA and suggest that PHA with at least one mental health disorder diagnosis are disproportionately impacted by sexual violence and stigma.

Attentional dysfunction in schizophrenia (SZ) contributes to the functional deficits ubiquitous to the disorder. Identifying the neural substrates of translational measures of attentional dysfunction would prove invaluable for developing therapeutics. Attentional performance is typically assessed via continuous performance tasks (CPTs), though many place additional cognitive demands with little cross-species test-relevance. Herein, event-related potentials (ERPs) were used to investigate the neurophysiological correlates of attention and response inhibition of SZ and healthy participants, whereas they performed the cross-species-translated five-choice CPT (5C-CPT). Chronically ill, medicated SZ patients and matched controls (n=25 SZ and 26 controls) were tested in the 5C-CPT, in conjunction with ERP and source localization assessments. The ERPs generated in response to correctly identified target and non-target trials revealed three peaks for analysis, corresponding to sensory registration (P1), response selection (N2), and response action (P3). Behavioral responses revealed that SZ patients exhibited impaired attention driven by impaired and slower target detection, and poorer cognitive control. ERPs revealed decreased N2 amplitudes reflecting poorer response selection for both target and non-target trials, plus reduced non-target P3s in SZ patients, the latter accounting for 37% of variance in negative symptoms. Source analyses revealed that the brain regions of significant differences localized to the left dorsolateral prefrontal cortex during response selection and the posterior cingulate cortex for cognitive processes. SZ patients exhibited impaired attention and cognitive control, characterized by less robust frontal and parietal ERP distributions across the response selection and cognitive response time windows, providing neurophysiological characterization of attentional dysfunction in SZ using the reverse-translated 5C-CPT.

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