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The deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.
It does not require great powers of observation to note the pervasiveness of Nazi Germany in contemporary U.S. cultural and political discourse. For better or worse, the discursive landscape is saturated with depictions of and references to Hitler, the Holocaust, and the Gestapo—an obsession visible everywhere, from the progressive left to the far right, from TV shows to Twitter feeds to video games. The allure of using the Third Reich as a rhetorical weapon may seem obvious enough in a hyperpartisan political climate, but the resonance of that historical period clearly extends well beyond politics. Indeed, National Socialism now functions as an all-purpose conceptual barometer that can be applied to conversations about all sorts of subjects. Over the past few years, scholars have sought to shape such discussions with an unusually heavy outpouring of projects that explore correlations between Nazi Germany and the United States. What they rarely address, however, is why Americans are so prone to invoking the Third Reich as a framework for thinking about life in their own country to begin with. No less important to consider are the implications of how that trend has taken on such a wide-ranging salience and sense of urgency lately. With these questions in mind, Bradley Nichols (History, University of Missouri) convened an interdisciplinary roundtable, composed not only of historians, but also scholars of U.S. politics and culture. He invited Jens-Uwe Guettel (History, Penn State University), Sabine Hake (Germanic Studies, University of Texas), Emanuela Kucik (English and Africana Studies, Muhlenberg College), Alexandra Minna Stern (English, University of California, Los Angeles), and S. Jonathan Wiesen (History, University of Alabama at Birmingham) to share their insights and reflect on the issues at stake.
1. The recent upsurge of scholarly interest in the relationship between Nazi Germany and the United States has mirrored a heightened level of popular curiosity in the topic. How do we explain the timing of this conjuncture? What, if anything, sets it apart from the long-standing current of fascination with parallels linking the two countries? Is there something unique going on here that transcends other overlaps in focus between academia and the public (past or present)?
Progress towards understanding the aetiology of major depression is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity.
To compare risk factor profiles for three subgroups of major depression according to episode context.
Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of major depression: postpartum depression (3581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) major depression phenotype excluding the two other contexts (34 699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with the polygenic risk scores (PRS) for major depression and with other risk factors previously associated with major depression (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education).
Major depression PRS was associated with all subgroups, but postpartum depression cases had higher PRS than heterogeneous major depression cases (OR = 1.06, 95% CI 1.02–1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Depression following diagnosis of a chronic disease had weaker association with neuroticism and reported trauma in adulthood and childhood relative to heterogeneous depression.
The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined aetiological insights.
OBJECTIVES/GOALS: Use an easily accessible medium to educate life science researchers and academic innovators interested in the commercialization of academic research at the University of Michigan (UM). METHODS/STUDY POPULATION: Life science research investigators and academic innovators interested in research commercialization and technology development from across the state of Michigan were invited to attend the Idea to Impact: The Translation & Commercialization of Academic Research webinar series, presented by Fast Forward Medical Innovation at the University of Michigan. The webinar series outlined the significance and critical milestones of developing novel therapeutics, medical devices, diagnostics, and digital health innovations, as well as essential collaborations with industry partners to translate a research-based idea into a product of impact. RESULTS/ANTICIPATED RESULTS: 113 investigators and innovators from 28 different institutions, organizations, and companies, registered for the webinar series. Results (N=24) of an evaluation immediately following each webinar revealed that 100% of respondents strongly agreed or agreed that the series was effective in helping them to identify and describe commercialization resources, including funding, education, and mentorship, available at the University of Michigan and within the state. Participants stated that they “loved the practical information” “shared” and that the series was a “great overview that inspired a lot more questions.” The Fast Forward Medical Innovation team was then able to consult with participants to connect them with additional resources. DISCUSSION/SIGNIFICANCE: The data suggests that easily accessible and digestible commercialization education can make navigating the academic entrepreneurial ecosystem easier for investigators and innovators. The recorded webinar series, Idea to Impact: The Translation & Commercialization of Academic Research, serves this purpose.
OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI â‰¥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 Â± 3.2 kg, P<0.01; liraglutide -2.7 Â± 3.2, P<0.01), while sitagliptin did not (-0.7 Â± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.
OBJECTIVES/GOALS: The University of Michigan Frankel Cardiovascular Center (FCVC) Innovation Challenge is an annual competition offering funding for innovative ideas to improve cardiovascular care. Due to the COVID-19 pandemic, administrators converted the recruitment process and pitch event to fully virtual. METHODS/STUDY POPULATION: We detail the process of converting the event from a hybrid process (virtual and in-person recruiting and in-person event) to a fully virtual one. Changes to the event included implementing a virtual recruiting process utilizing short video recordings as submission format; a new tool for storing and displaying submissions; fully virtual finalist selection and coaching; and a fully virtual pitch and judging event. The submission process tracked information about submissions that include the type of idea (process or product), role of team lead, and department of team lead. RESULTS/ANTICIPATED RESULTS: The FCVC Innovation Challenge was successfully converted to a fully virtual event. Methods and tools will be shared to allow similar institutions to replicate a successful virtual pitch event. These include methods and tools utilized to allow participants to describe their ideas, strategies to select and coach finalists, and to host a virtual pitch event. Data will be shared on the number of ideas and category (product/process) of projects submitted, and number and category of finalists selected. DISCUSSION/SIGNIFICANCE: This case review can demonstrate how institutions can use a similar virtual idea submission and pitch process to (1) catalyze innovative ideas that can impact patient care by accessing its communitys ideas and (2) fund innovative ideas that do not fit traditional mechanisms.
OBJECTIVES/GOALS: Ask the Experts: A Biomedical Innovation Forum, presented by Fast Forward Medical Innovation (FFMI) at the University of Michigan, provided an opportunity to educate biomedical innovators on life science investment trends and technology assessment criteria. METHODS/STUDY POPULATION: FFMI, in partnership with the U.S. Economic Development Administration, recruited an expert group of panelists to be featured at this virtual event. These life science investment experts provided insight on the strategy, timing, and best method for innovators to engaged investors, the specifics of what investors look for in technologies and project teams, and expectations of investors and project teams after the investment is secured. The panel presentation was followed by a poster presentation highlighting projects from the FFMI Hub at the University of Michigan, allowing innovators to have an open and constructive conversation with experts and attendees. RESULTS/ANTICIPATED RESULTS: There was a total of 73 registrants including academic faculty, biomedical innovators, and life science investment professionals from 21 different academic institutions, private companies, and other organizations. 50 attended the panel presentation and poster session. Results (N=5) of an evaluation of the event revealed that 100% of the respondents strongly agreed or agreed that the event met their expectations, while 80% strongly agreed or agreed that they would recommend the event to a colleague. Feedback from poster presenters was also strong with presenters exclaiming they “enjoyed the panel discussion and getting one-on-one time with the panelists,” as well as “a lot of great advice was given by the experts” and “I really liked the poster presentation part in which I got feedback from the investors.” DISCUSSION/SIGNIFICANCE: The data demonstrates how accelerating technology mining activities, proactively seeking and strengthening external partnerships with investors, and scaling commercialization education programs can have a positive impact on the development and launch of biomedical innovations.
Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.
To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.
We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.
Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.
Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.
ABSTRACT IMPACT: The successful conversion of an in-person biomedical research commercialization education course to a fully virtual and flipped experience (self-paced) allows greater participation from faculty investigators at CTSA institutions and serves as a model for similar educational programs intended to accelerate the translation of biomedical innovations to products of impact. OBJECTIVES/GOALS: Due to COVID-19, University of Michigan’s Fast Forward Medical Innovation developed new educational resources and leveraged virtual learning tools to convert a successful in-person research commercialization course to a fully virtual, flipped format and evaluated the effectiveness of the converted course compared to the in-person equivalent. METHODS/STUDY POPULATION: Two novel interactive modules (intellectual property and FDA regulation) and five instructional videos (customer discovery, value proposition, opportunity sizing, target product profile, and patent searches) were developed while Constant Contact and Zoom were used for a weekly progression of content delivery and to flip the course: (1) forming/testing value propositions, (2) intellectual property, (3) regulatory, (4) medical reimbursement, (5) business case development. A total of 32 faculty and graduate students completed the virtual, flipped course and submitted a post-course evaluation. Results of the converted course were compared to evaluation results from the in-person course. RESULTS/ANTICIPATED RESULTS: Open rates for the weekly email content were: (1)61%, (2)67%, (3)65%, (4)67%, and (5)59 %. Total views for the modules and videos were: IP-28, regulation-19, customer discovery-62, value proposition-21, opportunity sizing-66, target product profile-11, and patent searches-29. Evaluation results from the virtual course (n=22) were compared to mean results from the 5 previous in-person courses (n=42); 86% of virtual course respondents stated the course met the objectives compared to 85% of in-person respondents; 87% of virtual respondents stated the course met their expectations compared to 100% of in-person; 87% of virtual respondents said they would participate in a follow-up program compared to 94% in-person; 91% of virtual respondents would recommend the course to others compared to 97% of in-person. DISCUSSION/SIGNIFICANCE OF FINDINGS: Email open rates and content views suggest positive flipped participation. Overall, the converted course was comparable to the in-person course at meeting objectives, suggesting the virtual format is effective at delivering the course content and holds the potential for engaging a broader audience.
The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders.
To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD).
In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study.
The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons.
Multiple measures of depression can serve as a reliable approximation for case status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UK Biobank data.
Traditional training and funding mechanisms in academic health centers often do not support its faculty, staff, and trainees in evaluating and implementing innovative ideas, necessitating supplemental innovation programming. The University of Michigan (U-M) Frankel Cardiovascular Center partnered with U-M Fast Forward Medical Innovation (FMMI), a biomedical innovation and commercialization unit funded in part by the Clinical and Translational Science Award awarded to the Michigan Institute for Clinical & Health Research, to provide training and resources to advance ideas toward impacting patients. The program recruited faculty, trainees, staff, patients, and family members from multidisciplinary backgrounds. Engaging patients and family members expanded the ideas generated and furthered clinical relevance. Over two years, 11 project teams completed an 11-week, 16-session course on innovation and entrepreneurship concepts that incorporated workshops to progress ideas and develop a pitch for development funding. An increase in knowledge was reported in key innovation topics, such as customer discovery, assessing markets, and intellectual property. Participants reported an increase in project preparation, including obtaining stakeholder support, preparation of a development plan, readiness to apply for funding, and filing invention disclosures. This program can serve as a model for implementing training and funding mechanisms to advance innovative ideas.
Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.
Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).
Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10−3–3.94 × 10−7).
An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.
Between 2009 and 2013, the Fly on the Wall (FLY) leaked 58% of recommendation revisions with a median delay of 27 minutes relative to the IBES announcement time. We show that FLY improves price discovery, but leaked recommendations hamper brokers’ ability to offer price improvement on trades routed through them. Three major brokers sued FLY; using key court dates, we show significant wealth and real effects to the brokerage industry. Overall, the speed with which analyst recommendations are disseminated has led to more rapid price discovery at the expense of a decline in the scope of the sell-side research industry.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions.
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality.
Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = −0.90 (CBT; k = 27, 95% CI −1.11 to −0.68; moderate quality) to g = −1.26 (EMDR; k = 4, 95% CI −2.01 to −0.51; low quality). CBT and EA each had moderate–large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate–large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome.
The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences.
Background: Scrupulosity is a common yet understudied presentation of obsessive compulsive disorder (OCD) that is characterized by obsessions and compulsions focused on religion. Despite the clinical relevance of scrupulosity to some presentations of OCD, little is known about the association between scrupulosity and symptom severity across religious groups. Aims: The present study examined the relationship between (a) religious affiliation and OCD symptoms, (b) religious affiliation and scrupulosity, and (c) scrupulosity and OCD symptoms across religious affiliations. Method: One-way ANOVAs, Pearson correlations and regression-based moderation analyses were conducted to evaluate these relationships in 180 treatment-seeking adults with OCD who completed measures of scrupulosity and OCD symptom severity. Results: Scrupulosity, but not OCD symptoms in general, differed across religious affiliations. Individuals who identified as Catholic reported the highest level of scrupulosity relative to individuals who identified as Protestant, Jewish or having no religion. Scrupulosity was associated with OCD symptom severity globally and across symptom dimensions, and the magnitude of these relationships differed by religious affiliation. Conclusions: Findings are discussed in terms of the dimensionality of scrupulosity, need for further assessment instruments, implications for assessment and intervention, and the consideration of religious identity in treatment.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Background: Two ‘sibling’ disorders have been proposed for the fourthcoming 11th version of the International Classification of Diseases (ICD-11): post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). Examining psychological factors that may be associated with CPTSD, such as self-compassion, is an important first step in its treatment that can inform consideration of which problems are most salient and what interventions are most relevant. Aims: We set out to investigate the association between self-compassion and the two factors of CPTSD: the PTSD factor (re-experiencing, avoidance, sense of threat) and the Disturbances in Self-Organization (DSO) factor (affect dysregulation, negative self-concept and disturbances in relationships). We hypothesized that self-compassion subscales would be negatively associated with both PTSD and DSO symptom clusters. Method: A predominantly female, clinical sample (n = 106) completed self-report scales to measure traumatic life events, ICD-11 CPTSD and self-compassion. Results: Significant negative associations were found between the CPTSD DSO clusters of symptoms and self-compassion subscales, but not for the PTSD ones. Specifically it was also found that self-judgement and common humanity significantly predicted hypoactive affect dysregulation whereas self-judgement and isolation significantly predicted negative self-concept. Conclusions: Our results indicate that self-compassion may be a useful treatment target for ICD-11 CPTSD, particularly for symptoms of negative self-concept and affect dysregulation. Future research is required to investigate the efficacy and acceptability of interventions that have implicit foundations on compassion.