The LONI Image and Data Archive (IDA)11https://ida.loni.usc.edu/. is a repository for sharing and long-term preservation of neuroimaging and biomedical research data. Originally designed to archive ...strictly medical image files, the IDA has evolved over the last ten years and now encompasses the storage and dissemination of neuroimaging, clinical, biospecimen, and genetic data. In this article, we report upon the genesis of the IDA and how it currently securely manages data and protects data ownership.
•A review of the genesis and development of the LONI IDA data repository•A description of the repository containing clinical, imaging and genetic data from more than 70 studies•For over 15years the IDA has securely managed imaging, clinical, and genetic data.•10 neuroimaging file formats for MRI, fMRI, DTI, PET, CT, and SPECT data are handled.•Investigators in 68 countries have downloaded more that 7 million data sets from the IDA.
Seminal studies using squid as a model led to breakthroughs in neurobiology. The squid giant axon and synapse, for example, laid the foundation for our current understanding of the action potential ...1, ionic gradients across cells 2, voltage-dependent ion channels 3, molecular motors 4–7, and synaptic transmission 8–11. Despite their anatomical advantages, the use of squid as a model receded over the past several decades as investigators turned to genetically tractable systems. Recently, however, two key advances have made it possible to develop techniques for the genetic manipulation of squid. The first is the CRISPR-Cas9 system for targeted gene disruption, a largely species-agnostic method 12, 13. The second is the sequencing of genomes for several cephalopod species 14–16. If made genetically tractable, squid and other cephalopods offer a wealth of biological novelties that could spur discovery. Within invertebrates, not only do they possess by far the largest brains, they also express the most sophisticated behaviors 17. In this paper, we demonstrate efficient gene knockout in the squid Doryteuthis pealeii using CRISPR-Cas9. Ommochromes, the pigments found in squid retinas and chromatophores, are derivatives of tryptophan, and the first committed step in their synthesis is normally catalyzed by Tryptophan 2,3 Dioxygenase (TDO 18–20). Knocking out TDO in squid embryos efficiently eliminated pigmentation. By precisely timing CRISPR-Cas9 delivery during early development, the degree of pigmentation could be finely controlled. Genotyping revealed knockout efficiencies routinely greater than 90%. This study represents a critical advancement toward making squid genetically tractable.
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•The first gene knockout in a cephalopod•Tryptophan 2,3 dioxygenase is required for pigmentation in Doryteuthis pealeii•CRISPR-Cas9 is highly efficient in squid embryos
Crawford et al. report the first gene knockout in a cephalopod. Using CRISPR-Cas9 in squid embryos, they target a gene encoding tryptophan 2,3 dioxygenase, an enzyme involved in ommochrome pigment production. Knockouts are highly efficient in G0 animals, resulting in a near complete lack of pigmentation and over 90% disruption of the tdo locus.
Genomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the ...medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.
We analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons).
Many of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV-phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers.
Introduction
Women with addiction issues are under-researched, despite previous evidence that women’s needs are less understood than men’s and that services can overlook gender-specific issues. The ...majority of women in treatment are mothers and a significant number have contact with child welfare services. The voices of these women are needed to shape and influence evidence-based treatment and service development.
Aim
To examine reasons and rationale for participation in research in mothers with addiction issues and involvement with the child welfare system.
Method
Reflexive thematic analysis was used on interview transcripts from two qualitative studies. Individual themes from each study were combined and analysed to develop themes covering both studies and at different timepoints in process of child welfare assessment or removal of child/ren.
Results
Three themes were identified (1) altruism; (2) personal benefit; and (3) empowerment. These mothers wanted to help with research. However, they also participated with the hope that this might facilitate the return of their children or help them to access support or services. A change over time was evident and, in those further down the line from child removal, there was a stronger want for their voices to be heard in order to advocate for other women and create change in services.
The Image and Data Archive (IDA) is a secure online resource for archiving, exploring, and sharing neuroscience data run by the Laboratory of Neuro Imaging (LONI). The laboratory first started ...managing neuroimaging data for multi-centered research studies in the late 1990's and since has become a nexus for many multi-site collaborations. By providing management and informatics tools and resources for de-identifying, integrating, searching, visualizing, and sharing a diverse range of neuroscience data, study investigators maintain complete control over data stored in the IDA while benefiting from a robust and reliable infrastructure that protects and preserves research data to maximize data collection investment.
The Global Alzheimer's Association Interactive Network (GAAIN) aims to be a shared network of research data, analysis tools, and computational resources for studying the causes of Alzheimer's ...disease. Central to its design are policies that honor data ownership, prevent unauthorized data distribution, and respect the boundaries of contributing institutions. The results of data queries are displayed in graphs and summary tables, which protects data ownership while providing sufficient information to view trends in aggregated data and discover new data sets. In this article we report on our progress in sharing data through the integration of geographically-separated and independently-operated Alzheimer's disease research studies around the world.
•A shared data network is presented for studying the causes of Alzheimer's disease.•Geographically-separate/independently-operated data repositories are linked together.•Search interfaces allow investigators to view data trends without access to data.•Ownership of data is protected by displaying the results of queries as graphs.•Data is never copied to the central server disks nor distributed to investigators.
Recruiting participants to randomised controlled trials (RCTs) is often challenging, particularly when working with socially disadvantaged populations who are often termed 'hard-to-reach' in ...research. Here we report the recruitment strategies and costs for the Trial for Healthy Relationship Initiatives in the Very Early years (THRIVE), an RCT evaluating two group-based parenting interventions for pregnant women.
THRIVE aimed to recruit 500 pregnant women with additional health and social care needs in Scotland between 2014 and 2018. Three recruitment strategies were employed: (1) referrals from a health or social care practitioner or voluntary/community organisation (practitioner-led referral), (2) direct engagement with potential participants by research staff (researcher-led recruitment) and (3) self-referral in response to study advertising (self-referral). The number of referrals and recruited participants from each strategy is reported along with the overall cost of recruitment. The impact of recruitment activities and the changes in maternity policy/context on recruitment throughout the study are examined.
THRIVE received 973 referrals: 684 (70%) from practitioners (mainly specialist and general midwives), 273 (28%) from research nurses and 16 (2%) self-referrals. The time spent in antenatal clinics by research nurses each month was positively correlated with the number of referrals received (r = 0.57; p < 0.001). Changes in maternity policies and contexts were reflected in the number of referrals received each month, with both positive and negative impacts throughout the trial. Overall, 50% of referred women were recruited to the trial. Women referred via self-referral, THRIVE research nurses and specialist midwives were most likely to go on to be recruited (81%, 58% and 57%, respectively). Key contributors to recruitment included engaging key groups of referrers, establishing a large flexible workforce to enable recruitment activities to adapt to changes in context throughout the study and identifying the most appropriate setting to engage with potential participants. The overall cost of recruitment was £377 per randomised participant.
Recruitment resulted from a combination of all three strategies. Our reflections on the successes and challenges of these strategies highlight the need for recruitment strategies to be flexible to adapt to complex interventions and real-world challenges. These findings will inform future research in similar hard-to-reach populations.
International Standard Randomised Controlled Trials Number Registry ISRCTN21656568 . Retrospectively registered on 28 February 2014.
Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly ...identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc MCI converted; conversion to AD within 24 months of time period, and 36 in MCIs MCI stable; no conversion to AD within 24 months of time period), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.
The Informatics Core of the Alzheimer's Disease Neuroimaging Initiative has coordinated data integration and dissemination for a continually growing and complex data set in which both data ...contributors and recipients span institutions, scientific disciplines, and geographic boundaries. This article provides an update on the accomplishments and future plans.
Abstract Introduction The Global Alzheimer's Association Interactive Network (GAAIN) is consolidating the efforts of independent Alzheimer's disease data repositories around the world with the goals ...of revealing more insights into the causes of Alzheimer's disease, improving treatments, and designing preventative measures that delay the onset of physical symptoms. Methods We developed a system for federating these repositories that is reliant on the tenets that (1) its participants require incentives to join, (2) joining the network is not disruptive to existing repository systems, and (3) the data ownership rights of its members are protected. Results We are currently in various phases of recruitment with over 55 data repositories in North America, Europe, Asia, and Australia and can presently query >250,000 subjects using GAAIN's search interfaces. Discussion GAAIN's data sharing philosophy, which guided our architectural choices, is conducive to motivating membership in a voluntary data sharing network.
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