Evaluating the Utility of a Psychoeducational Serious Game (SPARX) in Protecting Inuit Youth From Depression: Pilot Randomized Controlled Trial

Background: Inuit youth in Northern Canada show considerable resilience in the face of extreme adversities. However, they also experience significant mental health needs and some of the highest adolescent suicide rates in the world. Disproportionate rates of truancy, depression, and suicide among Inuit adolescents have captured the attention of all levels of government and the country. Inuit communities have expressed an urgent imperative to create, or adapt, and then evaluate prevention and intervention tools for mental health. These tools should build upon existing strengths, be culturally appropriate for Inuit communities, and be accessible and sustainable in Northern contexts, where mental health resources are often scarce. Objective: This pilot study assesses the utility, for Inuit youth in Canada, of a psychoeducational e-intervention designed to teach cognitive behavioral therapy strategies and techniques. This serious game, SPARX, had previously demonstrated effectiveness in addressing depression with Māori youth in New Zealand. Methods: The Nunavut Territorial Department of Health sponsored this study, and a team of Nunavut-based community mental health staff facilitated youth’s participation in an entirely remotely administered pilot trial using a modified randomized control approach with 24 youths aged 13-18 across 11 communities in Nunavut. These youth had been identified by the community facilitators as exhibiting low mood, negative affect, depressive presentations, or significant levels of stress. Entire communities, instead of individual youth, were randomly assigned to an intervention group or a waitlist control group. Results: Mixed models (multilevel regression) revealed that participating youth felt less hopeless (P=.02) and engaged in less self-blame (P=.03), rumination (P=.04), and catastrophizing (P=.03) following the SPARX intervention. However, participants did not show a decrease in depressive symptoms or an increase in formal resilience indicators. Conclusions: Preliminary results suggest that SPARX may be a good first step for supporting Inuit youth with skill development to regulate their emotions, challenge maladaptive thoughts, and provide behavioral management techniques such as deep breathing. However, it will be imperative to work with youth and communities to design, develop, and test an Inuit version of the SPARX program, tailored to fit the interests of Inuit youth and Elders in Canada and to increase engagement and effectiveness of the program

A study of the relationship between invasive threat and attitudes toward outgroups

Using data from the UC-Berkeley California Survey (a/k/a the Field Poll), we will test a series of hypotheses about the relationship, which we expect to be positive, between real and perceived COVID19 threat and attitudes towards immigration, immigrants, and ethnoracial minorities. Sociological theory, prior research, and historical experience all suggest that immigrants are vulnerable during periods of infectious-disease threat. Drawing on her African fieldwork but generalizing to societies of all kinds, Douglas (1984) note the universal fear of pollution and the universality of rituals employed to protect the social body from contamination. Douglas argues that ritual contamination results from persons and things that are “out of place,” that enter domains in which are liminal, lacking a clear status. Work in this line has noted a homology in modern societies between rhetorical treatments, on the one hand, of immigrants, as outsiders inhabiting a liminal status, and, on the other, of infectious disease, both of which have been depicted dangerous forms of, respectively, social and corporeal penetration (Santa Ana 1999; Cisneros 2008). One may infer from this that concern about infectious disease may stimulate anti-immigrant attitudes among susceptible publics. And, indeed, the historical record contains many examples of immigrant scapegoating in the U.S. during public health emergencies like the typhus and cholera epidemics of the early 1890s (Markel 1999), the bubonic plague outbreaks of 1900-1908 (Chase 2004), and the 1917-18 flu pandemic (Kraut 2010). Since January, reports of hate crimes against Asians blamed for the rise of COVID19 have proliferated (Chapman 2020). Compared to work by historians, anthropologists, and discourse analysts, empirical social-scientific research has been relatively scarce. A recent study (Aaroe, Petersen and Arceneaux 2017) suggests that this elision of immigrant and infectious disease may have a biological foundation. Dutta and Rao (2014) propose that “anxieties about infectious disease not only prime concerns about foreigners as disease threats but also prime the concerns about cultural outgroups as sources of cultural contamination.” They conducted a survey experiment that demonstrated a decline in support for a path to citizenship for undocumented immigrants when respondents were primed with a fictionalized description of a contagious disease originating in a foreign country; and paired this with an historical study demonstrating that resistance to British colonialists was greater in parts of India that had experienced more severe exposure to a cholera epidemic several months earlier. The emergence of COVID19 as a contemporary pandemic offers an opportunity to explore the relationship between disease threat and attitudes toward immigrants in real time. This study takes advantage of a survey of ~9000 California registered voters, carried out by the UC-Berkeley Institute of Governmental Studies in April 2020, which included a large battery of questions about COVID19 and a number of items tapping attitudes towards immigrants and immigration. We will use data from this study to test several hypotheses about the relationship between (a) perceived vulnerability to COVID19 infection, (b) priming with questions about COVID19, and (c) local prevalence of COVID19 to (a) attitudes toward immigrants and (b) attitudes toward immigration. The results of this study will help to determine the validity of an influential body of theory on group boundaries and intergroup relations. If the hypotheses receive some support, the pattern of results (including variation in effects on attitudes toward different minority groups) will provide insight into the extent to which effects are specific to scapegoated groups or instead generalize to all groups perceived as outsiders to the ethnoracial mainstream. With respect to public policy, in so far as the hypotheses are confirmed, the results will alert civic leaders, law enforcement, educators, and others to challenges that may result from increased intergroup conflict and scapegoating of immigrant Americans during and in the wake of the current pandemic

Reflections on SPARX, a self-administered e-intervention for depression, for Inuit youth in Nunavut

Inuit youth in Canada endure significant mental health challenges, including geographic isolation, economic hardships, mental health stigma, and severely limited access to mental health services in remote Northern communities. Yet Inuit are also among the least likely of all youth in Canada to seek help when experiencing distress. This troubling reality highlights the need for an exploration of self-administered and discreet therapeutic interventions. Smart, Positive, Active, Realistic, X-Factor thoughts (SPARX) is a cognitive–behavioral therapy-based serious game, developed with Māori youth in New Zealand and designed to address depressive symptoms. Inuit wisdom and the scientific literature emphasize the need for any intervention to integrate evidence-based approaches with Inuit-specific cultural practices. Accordingly, to reflect on SPARX’s cultural appropriateness in their communities, 11 Inuit youth and seven community facilitators participated in semi-structured individual, paired, and focus group exit interviews. Participant feedback suggested that the program was engaging and promising as an intervention to improve mood and cognitive coping; however, youth also highlighted the need for a culturally appropriate adaptation of SPARX. By weaving Inuit culture into the game, they felt SPARX could be used to foster community resilience, cultural pride, and youth capacity and engagement while building mental health literacy. Overcoming systemic obstacles to mental health support for Inuit youth in Canada requires innovative, youth-centered approaches. SPARX represents one potential strategy

Evaluating the Utility of a Psychoeducational Serious Game (SPARX) in Protecting Inuit Youth From Depression: Pilot Randomized Controlled Trial (Preprint)

BACKGROUND Inuit youth in Northern Canada show considerable resilience in the face of extreme adversities. However, they also experience significant mental health needs and some of the highest adolescent suicide rates in the world. Disproportionate rates of truancy, depression, and suicide among Inuit adolescents have captured the attention of all levels of government and the country. Inuit communities have expressed an urgent imperative to create, or adapt, and then evaluate prevention and intervention tools for mental health. These tools should build upon existing strengths, be culturally appropriate for Inuit communities, and be accessible and sustainable in Northern contexts, where mental health resources are often scarce. OBJECTIVE This pilot study assesses the utility, for Inuit youth in Canada, of a psychoeducational e-intervention designed to teach cognitive behavioral therapy strategies and techniques. This serious game, SPARX, had previously demonstrated effectiveness in addressing depression with Māori youth in New Zealand. METHODS The Nunavut Territorial Department of Health sponsored this study, and a team of Nunavut-based community mental health staff facilitated youth’s participation in an entirely remotely administered pilot trial using a modified randomized control approach with 24 youths aged 13-18 across 11 communities in Nunavut. These youth had been identified by the community facilitators as exhibiting low mood, negative affect, depressive presentations, or significant levels of stress. Entire communities, instead of individual youth, were randomly assigned to an intervention group or a waitlist control group. RESULTS Mixed models (multilevel regression) revealed that participating youth felt less hopeless (&lt;i&gt;P&lt;/i&gt;=.02) and engaged in less self-blame (&lt;i&gt;P&lt;/i&gt;=.03), rumination (&lt;i&gt;P&lt;/i&gt;=.04), and catastrophizing (&lt;i&gt;P&lt;/i&gt;=.03) following the SPARX intervention. However, participants did not show a decrease in depressive symptoms or an increase in formal resilience indicators. CONCLUSIONS Preliminary results suggest that SPARX may be a good first step for supporting Inuit youth with skill development to regulate their emotions, challenge maladaptive thoughts, and provide behavioral management techniques such as deep breathing. However, it will be imperative to work with youth and communities to design, develop, and test an Inuit version of the SPARX program, tailored to fit the interests of Inuit youth and Elders in Canada and to increase engagement and effectiveness of the program. CLINICALTRIAL ClinicalTrials.gov NCT05702086; https://www.clinicaltrials.gov/ct2/show/NCT05702086 </sec

Training the next generation of Biostatisticians in West Africa: The Vanderbilt Nigeria Biostatistics Training Program (VN-BioStat)

Biomedical HIV research is growing in West Africa, but biostatistical expertise is lagging. The Vanderbilt-Nigeria Biostatistics Training Program (VN-BioStat) seeks to establish a research and training platform for biostatisticians doing HIV-related research in Nigeria. The objectives of the program are: (i) Host two Nigerian data scientists per year (a total of 10 over 5 years) at Vanderbilt University Medical Center to gain hands-on biostatistics training and experience via one-year fellowships. Eligible trainees will be junior investigators with PhDs or nearing completion of their PhDs in statistics or related fields, including mathematics and computer science. (ii) Conduct annual workshops in Nigeria to provide biostatistics training. Trainees will undertake biostatistics coursework and hands-on training and participate in mentorship as biostatisticians involved in HIV research. Trainees will be at Vanderbilt for a full year and be part of an active biostatistics department. They will be immersed in a dry-lab HIV biostatistics project in collaboration with a Nigerian HIV research project and lead a methodologically focused research project. They will also participate in a one-month research training/grant writing program in Nashville. The VN-BioStat program will build on the existing momentum of ongoing initiatives to enhance research capacity in Nigeria by developing biostatistics leadership. VN-BioStat trainees will interact with investigators from Nigeria to provide collaborative biostatistical assistance with study design and data analysis, thus gaining real-world experience that will benefit the trainees and the broader research community in Nigeria

A Nunavut Community-Directed Inuit Youth Mental Wellness Initiative: Making I-SPARX Fly

Inuit youth in Nunavut (NU) are resilient but face a protracted suicide crisis. The SPARX serious game and e-intervention, developed originally in New Zealand, teaches youth cognitive behavioural therapy (CBT) skills to ameliorate stress and depression. Inuit youth in NU reviewed and culturally adapted SPARX and an existing wellness outcome measure for Inuit. One hundred and twenty-one youth, aged 13 to 24, across NU then tested, played, and evaluated I(nuit)-SPARX, showing improvement in several areas of wellbeing post-play. Youth completed a CBT skills survey, engaged in sharing circles to assess CBT skill retention, and shared their thoughts about the usefulness and cultural fit of I-SPARX with Inuit Qaujimajatuqangit (IQ). Communication Skills, Listening Skills, and Problem Solving emerged as the most helpful learned CBT skills, and NU youth provided real-world examples of using I-SPARX skills to support their mental wellness. Several principles of IQ were exemplified and upheld in the content of the adapted SPARX tool and the process of the project as a whole. Empirically grounded, asynchronous e-tools, developed in collaboration with Inuit communities to ensure cultural specificity, may support psychological wellness in communities where mental health resources are scarce

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel–Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL’s coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype–phenotype relationships across complete genes

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles.

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel-Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL's coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes

Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques

AbstractZika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.Author summaryPre-existing immunity to one of the four DENV serotypes is known to increase the risk of severe disease upon secondary infection with a different serotype. Due to the antigenic similarities between ZIKV and DENV, it has been proposed that these viruses could interact in a similar fashion. Data from in vitro experiments and murine models suggests that pre-existing immunity to one virus could either enhance or protect against infection with the other. These somewhat contradictory findings highlight the need for immune competent animal models for understanding the role of cross-reactive antibodies in flavivirus pathogenesis. We examined secondary ZIKV or DENV infections in rhesus and cynomolgus macaques that had previously been infected with the other virus. We assessed the outcomes of secondary ZIKV or DENV infections by quantifying vRNA loads, clinical and laboratory parameters, body temperature, and weight for each cohort of animals and compared them with control animals. These comparisons demonstrated that within a year of primary infection, secondary infections with either ZIKV or DENV were similar to primary infections and were not associated with enhancement or reduction in severity of disease based on the outcomes that we assessed.</jats:sec