A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their current white matter integrity in the corpus callosum. Twenty-six children and adolescents with ASD, with and without a history of parent-managed behavioral intervention, underwent an MRI scan with a diffusion data acquisition sequence. We conducted tract-based spatial statistics and a region of interest analysis. The fractional anisotropy values (believed to indicate white matter integrity) in the posterior corpus callosum was significantly different across cases (exposed to parent-managed behavioral intervention) and controls (not exposed to parent-managed behavioral intervention). The effect was modulated by the intensity of the behavioral intervention according to a dose-response relationship. The current feasibility case-control study provides the basis for estimating the statistical power required for future RCTs in this field. In addition, the study demonstrated the effectiveness of purposely-developed motion control protocols and helped to identify regions of interest candidates. Potential clinical applications of diffusion tensor imaging in the evaluation of treatment outcomes in ASD are discussed

A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The cur rent feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diag nosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cogni tive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their current white matter integrity in the corpus callosum. Twenty-six children and adolescents with ASD, with and without a history of parent-managed behavioral intervention, underwent an MRI scan with a diffusion data acquisition sequence. We conducted tract-based spatial statistics and a region of interest analysis. The fractional anisotropy values (believed to indicate white mat ter integrity) in the posterior corpus callosum was significantly different across cases (exposed to parent-managed behavioral intervention) and controls (not exposed to parent managed behavioral intervention). The effect was modulated by the intensity of the behav ioral intervention according to a dose-response relationship. The current feasibility case control study provides the basis for estimating the statistical power required for future RCTs in this field. In addition, the study demonstrated the effectiveness of purposely-developed motion control protocols and helped to identify regions of interest candidates. Potential clini cal applications of diffusion tensor imaging in the evaluation of treatment outcomes in ASD are discussedThis study was supported by grants from Oakley Mental Health Foundation (project no. 3705925), The University of Auckland (Marsden Fund Near Miss Support Program), and through a research contract between ABA España and The University of Auckland (project no. CON02739); all awarded to JV

Appealing Features of Vocational Supports for Latino & non-Latino Transition Age Youth & Young Adult Consumers [English and Spanish versions]

A Spanish translation of this publication is available to download under Additional Files. Describes the Appealing Features of the Vocational Supports for Latino and Non-Latino Transition Aged Youth and Youth Adults (TAYYA) Consumers Study, which focuses on addressing employment disparities of young adults with a serious mental health condition (SMHC) by examining their lived experiences with established vocational support programs. The study pays particular attention to Latino TAYYA as they are a group at high risk for negative outcomes including high unemployment and low educational attainment compared to their white counterparts. They are also less likely to seek specialty mental health services and are the fastest growing racial ethnic group in the United States. Originally published as: Research in the Works, Issue 3, 2011. Also issued as Transitions RTC Research Brief 2, Mar. 2011

Overview of the MOSAiC expedition: Physical oceanography

Arctic Ocean properties and processes are highly relevant to the regional and global coupled climate system, yet still scarcely observed, especially in winter. Team OCEAN conducted a full year of physical oceanography observations as part of the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC), a drift with the Arctic sea ice from October 2019 to September 2020. An international team designed and implemented the program to characterize the Arctic Ocean system in unprecedented detail, from the seafloor to the air-sea ice-ocean interface, from sub-mesoscales to pan-Arctic. The oceanographic measurements were coordinated with the other teams to explore the ocean physics and linkages to the climate and ecosystem. This paper introduces the major components of the physical oceanography program and complements the other team overviews of the MOSAiC observational program. Team OCEAN’s sampling strategy was designed around hydrographic ship-, ice- and autonomous platform-based measurements to improve the understanding of regional circulation and mixing processes. Measurements were carried out both routinely, with a regular schedule, and in response to storms or opening leads. Here we present alongdrift time series of hydrographic properties, allowing insights into the seasonal and regional evolution of the water column from winter in the Laptev Sea to early summer in Fram Strait: freshening of the surface, deepening of the mixed layer, increase in temperature and salinity of the Atlantic Water. We also highlight the presence of Canada Basin deep water intrusions and a surface meltwater layer in leads. MOSAiC most likely was the most comprehensive program ever conducted over the ice-covered Arctic Ocean. While data analysis and interpretation are ongoing, the acquired datasets will support a wide range of physical oceanography and multi-disciplinary research. They will provide a significant foundation for assessing and advancing modeling capabilities in the Arctic Ocean

Experimental and modelling study of subsea oil releases: focusing on small leaks from an aging oilfield off the Norwegian Continental Shelf

With advances in exploration and extraction technology, oilfields that would otherwise have been ready for decommission are expected to produce oil for many more years. While beneficial to extract as much resource as possible from existing fields, this prolonged usage also increases the potential for oil leaks from aging pipelines. These pipeline leaks can produce high velocity conditions that emit plumes of small droplets of oil, gas and produced water. This is in contrast to large diameter blowouts where much larger droplets are expected. The exit parameters and resulting size distribution of oil droplets have a significant impact on the fate of oil in the environment. Using the SINTEF MiniTower in conjunction with a silhouette camera, the droplet size distributions for discharge conditions representative of small diameter, high velocity leaks of oil and produced water were obtained. These distributions were then used to empirically optimize the coefficients, A 8.5 and B 7.68, for use in droplet size prediction with the Modified Weber algorithm. These optimized coefficients predicted larger droplet sizes than the previously reported values, for small diameter, high velocity releases. A series of pipeline leaks and blowouts operating under different seasonal and release conditions were generated with the SINTEF oil spill modelling simulation tool, OSCAR. The Njord field was selected as a proxy for mature oilfields along the Norwegian Continental Shelf. The releases modelled produced thin and spread out surface slicks, which limited the effectiveness of response methods. The low surface oil thickness limited shoreline oiling, and the formation of tarballs would not be expected. This makes the Njord field an unlikely candidate source for oil pollution samples collected in the Frøya municipality region during an excursion in 2017. This fieldwork was carried out as part of the course Marine Organic Environmental Chemistry KJ3050 as a requisite of the Environmental Toxicology and Chemistry Master program at NTNU. Experimental and modelling studies are necessary to ensure appropriate monitoring and contingency planning for maturing oilfields

Appealing Features of Vocational Support Services for Hispanic and non-Hispanic Transition Age Youth and Young Adults with Serious Mental Health Conditions

Transition age youth and young adults (TAYYAs) diagnosed with serious mental health conditions (SMHCs) are at greater risk of being unemployed compared to their peers without SMHCs. Job counseling and job placement services are the greatest predictor of competitive employment, yet we have limited knowledge about what TAYYAs believe they need to obtain gainful employment. In person, qualitative interviews were conducted with 57 non-Hispanic and Hispanic TAYYAs with SMHCs enrolled in three vocational support programs in MA (Vocational Rehabilitation, Individual Placement and Support; the Clubhouse Model as described by the International Center for Clubhouse Development). Six themes emerged from the data: three themes were identified as social capital (supportive relationships, readily available workplace supports, and vocational preparation), two themes related to human capital (effective educational supports and work experience), and one theme related to cultural capital (social skills training). Unique features (Spanish-speaking staff and/or familiar in Latino culture, familial-like staff support) were frequently noted by Hispanic TAYYAs

The Meaning of Work for Young Adults Diagnosed With Serious Mental Health Conditions

OBJECTIVE: Despite the increased recognition of the importance of work for social and psychological well-being, the meaning of work for young adults with serious mental health conditions is understudied. This study uses a participatory action research approach to explore the economic, social and psychological significance of work for young adults diagnosed with psychiatric disabilities. METHOD: We conducted 57 one-hour semistructured interviews with young adults between the ages of 18 to 30 enrolled in 3 well established vocational support programs. NVivo 8 software was used to sort and systematically organize the interview data. RESULTS: Young adults with psychiatric disabilities work in part for financial independence from their family but also for additional reasons. Work provides the opportunity for social engagement and feelings of contributing to society as a whole. For some young adults, work provides the opportunity to enhance their self-esteem, self-confidence, and a positive self-image. For Latino young adults, work provides a way to cope with their mental illness. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our findings provide pertinent information for vocational rehabilitation services, recovery programs, and even parents on the importance of connecting young adults to jobs that enhance self-esteem and self-efficacy and are in line with their personal interests. Future research is needed to understand potential cultural and age differences in the meaning of work

Sequencing at lymphoid neoplasm susceptibility loci maps six myeloma risk genes

International audienceAbstract Inherited genetic risk factors play a role in multiple myeloma (MM), yet considerable missing heritability exists. Rare risk variants at genome-wide association study (GWAS) loci are a new avenue to explore. Pleiotropy between lymphoid neoplasms (LNs) has been suggested in family history and genetic studies, but no studies have interrogated sequencing for pleiotropic genes or rare risk variants. Sequencing genetically enriched cases can help discover rarer variants. We analyzed exome sequencing in familial or early-onset MM cases to identify rare, functionally relevant variants near GWAS loci for a range of LNs. A total of 149 distinct and significant LN GWAS loci have been published. We identified six recurrent, rare, potentially deleterious variants within 5 kb of significant GWAS single nucleotide polymorphisms in 75 MM cases. Mutations were observed in BTNL2, EOMES, TNFRSF13B, IRF8, ACOXL and TSPAN32. All six genes replicated in an independent set of 255 early-onset MM or familial MM or precursor cases. Expansion of our analyses to the full length of these six genes resulted in a list of 39 rare and deleterious variants, seven of which segregated in MM families. Three genes also had significant rare variant burden in 733 sporadic MM cases compared with 935 control individuals: IRF8 (P = 1.0 × 10−6), EOMES (P = 6.0 × 10−6) and BTNL2 (P = 2.1 × 10−3). Together, our results implicate six genes in MM risk, provide support for genetic pleiotropy between LN subtypes and demonstrate the utility of sequencing genetically enriched cases to identify functionally relevant variants near GWAS loci

Novel pedigree analysis implicates DNA repair and chromatin remodeling in multiple myeloma risk

<div><p>The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance–a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs. One genome-wide significant 1.8 Mb shared segment was found at 6q16. Exome sequencing in this region revealed predicted deleterious variants in <i>USP45</i> (p.Gln691* and p.Gln621Glu), a gene known to influence DNA repair through endonuclease regulation. Additionally, a 1.2 Mb segment at 1p36.11 is inherited in two Utah HRPs, with coding variants identified in <i>ARID1A</i> (p.Ser90Gly and p.Met890Val), a key gene in the SWI/SNF chromatin remodeling complex. Our results provide compelling statistical and genetic evidence for segregating risk variants for MM. In addition, we demonstrate a novel strategy to use large HRPs for risk-variant discovery more generally in complex traits.</p></div

Nguyen van Tuong

Acknowledgements Funding for the study described in this report was provided by the Buffett Foundation and Family Health International. The views expressed in this report are those of the authors and do not necessarily reflect those of the Buffett Foundation or of Family Health International. The authors wish to thank the following people for their assistance with this study and the production of this report