bluuebunny/crossref_metadata_2025 huggingface dataset:
93096 Does gender matter? Gender differences in the relationship between resting-state functional connectivity and emotion regulation in alcohol use disorder.
Authors: Nyoi Kai Xuan , Koithan Emily , Hendrickson Timothy , Verdoorn Hannah , Gilmore Casey , Mueller Bryon O. , Kushner Matt , Lim Kelvin O. , Camchong Jazmin
Published: March 2021

ABSTRACT IMPACT: Our research has the potential to impact human health by identifying gender specific neural markers of emotion regulation in alcohol use disorder. OBJECTIVES/GOALS: Emotion dysregulation is known to be mediated by altered functional organization of the limbic system in addiction. This preliminary study sought to identify gender effects in the association between emotion regulation and resting-state functional connectivity (rsFC) of a negative affect network. METHODS/STUDY POPULATION: 55 individuals receiving treatment for alcohol use disorder (˜2 weeks of abstinence) were recruited for this study and included in this analysis (N=55; Age: M=41.78, SD=10.66; 21 females). RsFC within a network involved in the withdrawal/negative affect stage of addiction and Personality Inventory for DSM-5 (PID-5) metrics were collected from all participants. RsFC data were preprocessed using the Human Connectome Project pipelines. Correlations between (a) rsFC within the withdrawal/negative affect network and the (b) scores of the negative affect subscale of the PID-5 instrument were conducted for each gender separately. RESULTS/ANTICIPATED RESULTS: Independent samples t-test showed a statistically significant gender difference in the PID-5 negative affect scores (Males: M=1.02, SD=0.66; Females: M=1.53, SD=0.51); t(55)=-3.002, p=0.004. Only females showed a significant correlation between rsFC within the withdrawal/negative affect network and negative affect scores of the PID-5 (r=0.51, p<0.05). Fisher r-to-z test showed significant gender differences (z=-1.91; p=0.03, 1-tailed) in correlations coefficients representing the relationship between rsFC of the withdrawal/negative affect network and negative affect (PID-5 subscale). DISCUSSION/SIGNIFICANCE OF FINDINGS: Preliminary findings suggest that the relationship between neural networks mediating emotion regulation and negative affect is only found in females. These results provide valuable data to inform personalized chemical dependency treatment that targets emotion regulation specific to females.
16461 Comparison of voxel intensity standardization methods in head and neck cancer magnetic resonance imaging
Authors: Wahid Kareem A. , He Renjie , McDonald Brigid A. , Anderson Brian M. , Salzillo Travis , Mulder Sam , Wang Jarey , Sharafi Christina Setareh , McCoy Lance A. , Naser Mohamed A. , Ahmed Sara , Sanders Keith L. , Mohamed Abdallah S.R. , Ding Yao , Wang Jihong , Hutcheson Kate , Lai Stephen Y. , Fuller Clifton D. , van Dijk Lisanne V.
Published: March 2021

ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.
44499 Heterogeneity of treatment effect among patients with type 2 diabetes and body mass index >=27kg/m^2 in the Jump Start Study
Authors: Kobe Elizabeth A. , Crowley Mathew J. , Jeffreys Amy , Yancy William S. , Zervakis Jennifer , Edelman David E. , Coffman Cynthia J.
Published: March 2021

ABSTRACT IMPACT: This is the first study to use QUINT analyses to examine heterogeneity of treatment effect for group medical visits among individuals with type 2 diabetes. QUINT is a data driven method that assumes no a priori assumptions regarding effect moderators - an important step in the path towards personalized medicine. OBJECTIVES/GOALS: To examine heterogeneity of treatment effect (HTE) in Jump Start, a trial that compared the effectiveness of group medical visits (GMVs) focused on medication management only versus the addition of intensive weight management (WM) on glycemic control for patients with type 2 diabetes and body mass index >=27kg/m^2. METHODS/STUDY POPULATION: Jump Start patients (n=263) were randomized to a GMV-based medication management plus low carbohydrate diet-focused WM program (WM/GMV; n = 127) or GMV-based medication management only (GMV; n = 136) for diabetes control. We used QUalitative INteraction Trees (QUINT), a tree-based clustering method, to determine if there were subgroups of patients who derived greater benefit from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Outcome was hemoglobin A1c (HbA1c). We conducted internal validation via bootstrap resampling to estimate bias in the range of mean outcome differences among arms. RESULTS/ANTICIPATED RESULTS: QUINT analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV alone (mean difference in HbA1c improvement = 1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen levels, GMV alone was better than WM/GMV (mean difference in HbA1c improvement = 1.51%). Internal validation resulted in moderate corrections in the mean HbA1c differences between arms; however, differences remained in the clinically significant range. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among patients with diabetes and BMI>=27kg/m^2, a low-carbohydrate, weight loss focus may better improve HbA1c in those who have never attempted weight loss. A medication management focus may be better in those who have attempted weight loss and have lower cholesterol and blood urea nitrogen.
16185 Iowa Implementation for Sustainability Framework: Specification and validation
Authors: Cullen Laura , Hanrahan Kirsten , Edmonds Stephanie W. , Reisinger Heather Schacht , Wagner Michele
Published: March 2021

ABSTRACT IMPACT: Framework is designed to aid selection of implementation strategies to promote adoption and sustainability of EBP to improve health care quality, safety and value. OBJECTIVES/GOALS: An application-oriented implementation framework based on Diffusion of Innovation theory, identified 81 strategies for clinician-use within four implementation phases. The goal of this research was to further specify strategies based on emerging implementation science and establish external validity. METHODS/STUDY POPULATION: An iterative mixed-methods process guided framework revisions. First, individuals (n=1,578) requesting use of the framework over the last seven years were sent an electronic questionnaire. Evaluation captured usability, generalizability, accuracy of phases, and implementation phases for each of 81 strategies. Second, nurses who use the framework pile sorted strategies for multidimensional scaling and hierarchical analysis using Anthropac software. Third, a panel of five EBP/implementation experts used data and a consensus process to add clarity with the naming, and further specify strategies. RESULTS/ANTICIPATED RESULTS: Survey respondents (n = 127, 8% response) were nurses (94%), at least Master’s educated (94%), from health systems (52%) or academia (31%), in the U.S. (84%). The framework, rated on a four-point scale (1 = not/strongly disagree to 4 = very/strongly agree; reported are ratings 3 and 4) was deemed useful (92%), generalizable (100%), and with accurate timing (96%). 51 participants linked strategy timing to a single phase (54 strategies, 66.7%, p<0.05, Cochran’s Q); most strategies (30) matched the original model. Pile sorting (n=23) generated a concept map and hierarchical clusters of groups. Experts used these data and implementation science to specify each strategy and revise the framework. DISCUSSION/SIGNIFICANCE OF FINDINGS: The Iowa Implementation for Sustainability Framework (IISF) offers a typology to guide implementation for healthcare improvements. This study specifies 77 implementation strategies, confirms four phases, identified 10 domains, and begins to establish external validity for the framework.
11554 Getting the Grant: Assessment of a Monthly Grant Writing Group for Junior Investigators
Authors: Aleksunes Lauren , Ebanks Yasheca , Chen Suzie
Published: March 2021

ABSTRACT IMPACT: NJ ACTS provides mentored coaching in NIH grant writing for early stage investigators. OBJECTIVES/GOALS: Launching an independent academic careers requires the ability to effectively communicate the purpose and impact of biomedical research in order to obtain extramural funding. We sought to develop and evaluate an interactive grant writing group of junior faculty and senior postdoctoral fellows mentored by trained coaches. METHODS/STUDY POPULATION: Participants meet monthly for 1 hour to peer review Specific Aims pages for grant applications to NIH and private foundations. Sessions are moderated by two senior faculty trained as coaches by the National Research Mentoring Network. Participant grant submission and review of the program are collected annually. RESULTS/ANTICIPATED RESULTS: From 2019-2020, 15 faculty and 2 postdoctoral fellows participated in the grant writing group with an average of 5.7 participants each month. Over the year, participants submitted 53 grant applications (68% submitted to NIH with the majority being R21 or R01 grant mechanisms). Half of grants submitted were discussed during peer review sessions. Of the grants reviewed, 42% were funded or near/below the funding payline. Using a 5-point Likert scale, participants highly rated the quality of coaching (mean/SD: 4.9 ±0.2), time discussing their research (mean/SD: 4.5 ±0.8), and the input from other participants (mean/SD: 4.5 ±0.5). DISCUSSION/SIGNIFICANCE OF FINDINGS: In conclusion, a monthly meeting of junior investigators hosted by two grant writing coaches is an effective means to receive peer review of grant application aims and support submissions for extramural funding.
24402 Grounded Theory Model for Adherence to Home Exercise among People with a Mobility Disability
Authors: Wilroy Jereme , Herbey Ivan , Ivankova Nataliya , Rimmer James
Published: March 2021

ABSTRACT IMPACT: Future exercise interventions for people with mobility disability should be tailored to the level of the individual and responsive to intervention adherence. A promising area of research is the use of adaptive interventions as a mechanism for tailoring and 'titrating’ the intervention based on data obtained during early intervention stages. OBJECTIVES/GOALS: The purpose of the study was to understand adherence to a home-based exercise trial delivered to people with a mobility disability. The objective was to develop a multi-dimensional model for engaging and retaining participants not adhering to an exercise trial by using a grounded theory approach involving both qualitative and quantitative data. METHODS/STUDY POPULATION: An exercise trial utilized telehealth technology to deliver a home-based exercise intervention for adults with a mobility disability. In order to understand factors of adherence to the exercise trial, a mixed methods study design was used involving baseline data and semi-structured interviews. Maximum variation sampling was used to select participants based on level of adherence, gender, race, and functional level. Categorization based on adherence to exercise videos during the first 12 weeks of the intervention included 3 groups: 1) high adherence (≥80% weekly median exercise video minutes viewed), 2) sub-optimal adherence (< 80% but ≥20%), and 3) low adherence (< 20%). Interviews were conducted with 10 participants in each group (n = 30) and data were analyzed using a grounded theory approach. RESULTS/ANTICIPATED RESULTS: A sample of 30 participants from a large pragmatic, home-based exercise trail have completed interviews. All interviews were transcribed and uploaded to NVivo software for coding. Emerging codes include lack of time to exercise, inappropriate exercise intensity, and lack of support for exercise. Using grounded theory approach, results include: 1) identifying risk factors for low adherence to a home-based exercise program delivered to people with mobility disability, 2) discovering themes for not responding to program activities in a home-based exercise program for adults with physical disabilities, and 3) determining the relationships between variables that emerge from thematic and statistical analyses. A model for adherence to home exercises among people with mobility disability will be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: People with a mobility disability are more susceptible to adopting sedentary lifestyles, which result in poor psychosocial and physical health outcomes. There is a clear and pressing need for designing future home-based exercise interventions with a greater level of customization for participants who have low to non-adherence.
46920 Engagement and co-creation in a DNA integrity cohort study
Authors: Arrieta Martha I. , Parker L. Lynette , Bonner Chantel M. , Sobol Robert W.
Published: March 2021

ABSTRACT IMPACT: Our work is demonstrative of the value embedded in community engagement as a vehicle to facilitate and expand the focus of translational research. OBJECTIVES/GOALS: To develop a community-informed recruitment process for a population-based DNA integrity longitudinal study aiming to document the average amount of DNA damage as well as DNA repair capacity in a cohort of community-dwelling individuals. METHODS/STUDY POPULATION: The three-member Community Engagement team (CE Team) partnered with a ten-person Community Advisory Board (CAB) to develop recruitment procedures and materials. Through an iterative process taking place over 13 meetings, CAB members answered questions about community context, appropriate recruitment approaches, and tone of communication with potential study participants. They also collaborated in the creation of outreach materials, informational booklets, and the informed consent document. The CAB’s input was recorded in meeting notes that informed successive versions of the materials. The CE Team held post-meeting debriefs to develop consensus on lessons learned and next steps. RESULTS/ANTICIPATED RESULTS: CAB input generated a five-step recruitment process. It informed approaches to communications with potential participants and resulted in a set of printed recruitment materials. Furthermore, the CAB pushed the CE Team and laboratory scientists to think beyond study participation to a comprehensive view of respectful engagement including notification of elected officials and other community institutions. By sharing personal anecdotes and asking how this study would reflect their lived experiences and/or contribute to their communities, CAB members inspired the university team to recognize the environmental context that may underlie DNA damage in residents of an underserved community. DISCUSSION/SIGNIFICANCE OF FINDINGS: The CAB was very effective in generating tools for recruitment. Moreover, CAB members provided insights beyond those originally sought by the CE Team, regarding broader engagement and a focus of future research relevant to the needs of both the community and the university researchers.
82786 Quantification of the Accuracy of Stereotactic Radiosurgery using Surface Guided Imaging with 3D Printed Head Phantoms
Authors: Bry Victoria , Saenz Daniel , Pappas Evangelos , Papanikolaou Niko , Rasmussen Karl
Published: March 2021

ABSTRACT IMPACT: This work assesses clinical implementation of a surface guided imaging system to improve the accuracy radiation delivery for treatment of brain lesions using a patient CT derived head phantom. OBJECTIVES/GOALS: Advancements in radiotherapy design have made clinical demand for efficient and accurate methods to deliver stereotactic radiosurgery (SRS) for treatment of intracranial lesions. This study assesses the potential of using surface guided imaging for setup using a 3D patient specific head phantom. METHODS/STUDY POPULATION: A single isocenter, multiple metastases SRS plan was generated on a CT derived RTsafe Prime phantom made of tissue equivalent materials and a polymer gel insert. Five targets of varying diameters were treated with 8Gy of radiation using two different positioning techniques. The first gel insert was irradiated within the phantom according to internal alignment with standard orthogonal x-ray imaging while the second setup used surface guided imaging, based on external anatomy. 42 hours after irradiation, the phantom was scanned in a head coil using a 1.5T MRI. MR images were fused with the patient CT data and structure set to further evaluate calculated and measured dose distributions. RESULTS/ANTICIPATED RESULTS: Discrepancies in phantom setup according to standard orthogonal x-ray imaging compared to surface guided imaging demonstrated to be <1mm in each translational (vertical, longitudinal, and lateral) and angular (rot, roll, pitch) directions. The 3D gel inserts permitted spatial analysis to compare dose distributions of measured values to those calculated in a treatment planning system (TPS). 3D GI (Gamma Index) analysis showed good alignment in high dose regions and resulted in passing rates >94% (5%/2mm) and >87% (3%/2mm). Finally, 3 of 5 targets showed better 3D GI passing rates and less geometric offset for positioning with the surface guided imaging. DISCUSSION/SIGNIFICANCE OF FINDINGS: 3D spatial analysis of human like phantoms demonstrated that patient positioning according to external anatomy performed comparable to standard methods aligning to the internal anatomy, for a multiple met SRS treatment.
11979 Using whole-exome and mtDNA sequencing to develop a testing algorithm for diagnosis of mitochondrial disease in Puerto Ricans
Authors: Albino Elinette , Buxo Carmen , Scaglia Fernando , Santiago-Cornier Alberto
Published: March 2021

ABSTRACT IMPACT: Alterations in mitochondrial metabolism affect any tissue, especially those with the highest demand for energy. As the symptoms and clinical manifestations are heterogenous, disease diagnosis is challenging. The implementation of genetic-first approach in the diagnosis of mitochondrial diseases will expedite confirmation, treatment, management, and counseling of affected Puerto Rican individuals. OBJECTIVES/GOALS: Mitochondrial diseases are rare, and diagnosis is complex due to the heterogeneity of clinical manifestations. We aim to develop and implement a testing algorithm using a genetics-first approach, facilitating the identification of variants that contribute to mitochondrial disease’s etiology and influence onset and progression in Puerto Ricans. METHODS/STUDY POPULATION: This is a cross-sectional study for characterizing clinical laboratory results from profiles used to evaluate metabolic diseases in individuals with suspected mitochondrial disorders from 2018 to 2021. A subset of 25 individuals from biochemical profile will be recruited to analyze their medical and family history, metabolic biomarkers in blood and urine, hearing test, imaging and chromosomal microarray. The implementation of a genetic testing algorithm using whole exome and mitochondrial DNA sequencing will be performed in a subset of 11 randomized individuals. Descriptive analysis will be reported, including a catalog of all variants. Multivariate analysis will be performed to estimate the statistical association between variants and phenotypes reported and adjusting for potential confounders. RESULTS/ANTICIPATED RESULTS: The biochemical profile of pediatric Puerto Rican individuals suspected of having mitochondrial diseases will be altered and can be used to differentiate among other metabolic causes. We expect to find altered levels of lactate, pyruvate and carnitines in serum, as well as altered organic acids in urine. The implementation of a testing algorithm using both, mitochondrial DNA and whole exome sequencing as first approach will be enabling the identification of disease-causing variants, thus enhancing and confirming the diagnosis of mitochondrial disease in Puerto Ricans. We will be able to identify rare/novel variants specific to our Hispanic population, for both nuclear and mitochondrial DNA. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will help to characterize the metabolic profile of pediatric Puerto Ricans. No previous study has been reported that describes testing algorithms for genetic diagnosis of mitochondrial disease in our population. Variants found will contribute to a deep understanding of the genetic contribution to phenotypes and disease susceptibility.
10040 Proactive and responsive COVID-19 multidisciplinary research support through the University of Minnesota’s Clinical Research Support Center
Authors: Odlaug Brian L. , Crevel Francoise , Tosun Nicole , Lee Ryan , McKenzie Carrie , Bellin Melena , Prich Brenda , Weisdorf Daniel
Published: March 2021

ABSTRACT IMPACT: In a global pandemic where data development and dissemination are integral to combating the disease, the Clinical Research Support Center at the University of Minnesota provides a model of comprehensive virtual support, helping to attain and disseminate novel research on COVID-19, its individual and community impact, and treatment initiatives/outcomes. OBJECTIVES/GOALS: The pandemic created massive disruption to the conduct of clinical research with an unprecedented reorientation towards COVID-19. In this fast-paced environment, the Clinical Research Support Center (CRSC) rapidly developed innovative means of supporting diverse research initiatives. METHODS/STUDY POPULATION: The CRSC rapidly transitioned into a virtual environment and developed tools for the clinical research community to enhance remote clinical trial start up. This includes supporting remote consent, eBinders, COVID-19 research training for clinical staff, and easier identification of potential participants for COVID-19 studies; all through virtual support. Support provided research teams guidance on study protocols, regulatory requirements, informatics, biostatistics, financial management, recruitment strategies to support critical, urgent COVID-19 research. We outline proactive examples of how the CRSC now provides support to research teams through the pandemic. RESULTS/ANTICIPATED RESULTS: From March-November 2020, 116 COVID-19 projects received virtual support from the CRSC for COVID-19 research: disease understanding (n=27), treatment (n=23), pandemic impact (n=20), clinical care innovation (n=18), disease control and surveillance (n=10), prevention (n=9), detection (n=5), and impact on minorities (n=4). The diversity of these studies demonstrates the demand for and benefit from multidisciplinary expertise supporting study design and implementation. Through successful articulation and acceleration of research activities, the CRSC met the need for speed and rapidly adapted to new challenges created by the pandemic. DISCUSSION/SIGNIFICANCE OF FINDINGS: In a global pandemic where rapidly changing barriers to research is ongoing, through multidisciplinary efforts, the CRSC continues to provide comprehensive, virtual support to attain and disseminate novel research on COVID-19, its individual and community impact, and treatment initiatives/outcomes.
44190 Comparing the Accuracy of Different Tools in Identifying Glaucoma Medication Non-adherence
Authors: Cho Juno , Niziol Leslie , Lee Paul , Heisler Michele , Resnicow Kenneth , Musch David C , Newman-Casey Paula Anne
Published: March 2021

ABSTRACT IMPACT: Medication non-adherence is a widespread problem in glaucoma care, and this abstract shows that a free and easy to implement tool can be used to accurately screen and identify patients who are not adherent to their glaucoma medication. OBJECTIVES/GOALS: To compare the accuracy of pharmacy refill data and five measures of self-reported adherence in identifying patients with poor electronically monitored glaucoma medication adherence. METHODS/STUDY POPULATION: Glaucoma patients (age ≥40, poor self-reported adherence, and ≥1 medication) recruited at the University of Michigan completed five surveys of adherence and 3-months of electronically monitored medication adherence; pharmacy refill data were obtained. Electronically monitored adherence was summarized monthly as percent of doses taken on time. Median monthly adherence ≤80% was considered non-adherent. Pharmacy refill data were reported as the proportion of days covered. The accuracy of the measures in predicting ≤80% adherence was assessed with receiver operating characteristic curves such as estimation of area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS/ANTICIPATED RESULTS: 95 patients completed electronic monitoring with a median monthly adherence of 74% (±21%); 53 patients (56%) were non-adherent. Pharmacy refill adherence was not significantly correlated with electronically monitored medication adherence (r=0.12, p=0.2). A single-item adherence question (‘Over the past month, what percentage of your drops do you think you took correctly?’) had the largest correlation with electronically monitored adherence (r=0.47, p<0.0001), the largest AUC for predicting non-adherence (AUC= 0.76, [95% Confidence Interval = 0.66, 0.87]), best accuracy (71%, [61, 82]), and good sensitivity (84%, [73, 96]). DISCUSSION/SIGNIFICANCE OF FINDINGS: A free, single-item screening question ('Over the past month, what percentage of your drops do you think you took correctly?') offers an easy-to-implement tool for identifying glaucoma patients with poor medication adherence in clinical practice.
77099 Implementation of the Capute Scales and Prechtl’s General Movement Assessment in Infants with Single Ventricle Physiology
Authors: Johnson TL , Raiees-Dana H , Escapita A
Published: March 2021

ABSTRACT IMPACT: Through this research, I will transform the standard of care for infants with single ventricle physiology by incorporating the Capute Scales and General Movement Assessment into day-to-day clinical care for these infants, leading to early detection of neurodevelopmental disabilities and access to proven therapies. OBJECTIVES/GOALS: Our objective was to establish a new protocol to detect and quantify developmental delays in multiple domains in infants with single ventricle physiology, a type of congenital heart disease. This population is at high risk for neurodevelopmental disabilities. METHODS/STUDY POPULATION: We implemented a novel protocol using the Capute Scales and General Movement Assessment to evaluate early language, cognitive, and motor development in infants with single ventricle physiology. The infants were evaluated between 1-5 months of age in the cardiac neurodevelopmental program. We defined our primary outcomes as (1) language and (2) cognitive developmental quotients as per the Capute Scales and (3) results of the General Movement Assessment. We hypothesized that infants with single ventricle physiology would have typical language and cognitive development and normal General Movement Assessment results at their initial evaluation. RESULTS/ANTICIPATED RESULTS: We recruited ten infants with single ventricle physiology. All ten infants had typical language development, and nine of the ten had typical cognitive development, as measured by the Capute Scales. All of the infants had gross motor delay. Due to medical instability, we only evaluated four infants with the General Movement Assessment. All four of the infants had a normal result, suggesting that their central nervous system motor pathways were maturing appropriately. In future studies, we will track the neurodevelopmental outcomes of each participant as they mature. We expect to see a decrease in expressive language development and preserved receptive language and cognitive development. DISCUSSION/SIGNIFICANCE OF FINDINGS: The combination of General Movement Assessment and Capute Scales in the evaluation of infants with single ventricle physiology will provide early identification and intervention for these high-risk children, allowing access to proven treatments and therapies.
14C INTERCOMPARISON EXERCISE ON BONES AND IVORY SAMPLES: IMPLICATIONS FOR FORENSICS
Authors: Quarta G , Molnár M , Hajdas I , Calcagnile L , Major I , Jull A J T
Published: March 2021

The application of accelerator mass spectrometry radiocarbon (AMS 14C) dating in forensics is made possible by the use of the large excursion of the 14C concentration in the post-WWII terrestrial atmosphere due to nuclear testing as a reference curve for data calibration. By this approach high-precision analyses are possible on samples younger than ∼70 years. Nevertheless, the routine, widespread application of the method in the practice of forensics still appears to be limited by different issues due to possible complex interpretation of the results. We present the results of an intercomparison exercise carried out in the framework of an International Atomic Energy Agency (IAEA) CRP-Coordinated Research Project between three AMS laboratories in Italy, Hungary, and Switzerland. Bone and ivory samples were selected with ages spanning from background (>50 ka) to 2018. The results obtained allow us to assess the high degree of reproducibility of the results and the remarkable consistency of the experimental determinations.
(In)Decent work conditions and quality care: an issue for long-term care policy
Authors: Gil Ana Paula
Published: March 2021

The availability of informal care will remain a key factor influencing future demand for formal services and the analysis cannot be dissociated from formal care. Based on the ‘unpaid care work–paid work–paid care work circle’, proposed by the International Labour Office, this paper focuses on the individual, interpersonal and organisational determinants that most influence quality care. This paper is based on 40 semi-structured interviews with care workers, in 16 Portuguese care homes, in one council in the metropolitan area of Lisbon. In spite of social change processes in the care worker profession in Portuguese nursing homes, in the last decade, in terms of numbers, age and education, the interviews allowed me to unveil qualitatively what the numbers hid: precarious working conditions, insufficient staffing, excessive workloads and long working hours, high rotation and insufficient skills. All these determinants have consequences not only on the quality of the care that these care workers can offer, but also on their physical and mental health, job satisfaction and work environment. The high demand of care needs due to the ageing of the population, calls for continued efforts in improving working conditions, and a national strategy to promote recruitment of a diverse, younger and more-qualified workforce. The professionalisation of care work must be integrated with migration and employment policies (improvement of job quality and working conditions).
Nuclear weapons, extinction, and the Anthropocene: Reappraising Jonathan Schell
Authors: van Munster Rens , Sylvest Casper
Published: March 2021

In the Anthropocene, International Relations must confront the possibility of anthropogenic extinction. Recent, insightful attempts to advance new vocabularies of planet politics tend to demote the profound historical and intellectual links between our current predicament and the nuclear age. In contrast, we argue that it is vital to revisit the nuclear-environment nexus of the Cold War to trace genealogies of today's intricate constellation of security problems. We do so by reappraising the work of Jonathan Schell (1943–2014), author of The Fate of the Earth (1982), who came to regard extinction as a defining feature of the nuclear age. We show how a deep engagement with nuclear weapons led Schell to an understanding of the Earth as a complex, delicate ecology and fed into a sophisticated, Arendtian theory of extinction. Despite its limitations and tensions, we argue that Schell's work remains deeply relevant for rethinking human–Earth relations and confronting the Anthropocene.
Mantle Flow and Dynamics Beneath Central‐East China: New Insights From P‐Wave Anisotropic Tomography
Authors: Jiang Guoming , Zhang Guibin , Zhao Dapeng , Lü Qingtian , Shi Danian , Li Hongyi , Li Xinfu
Published: March 2021

Massive lithospheric thinning occurred in eastern China and large‐scale magmatism in South China occurred in the Mesozoic. Some geodynamic models have been proposed to explain their mechanisms, but are not consistent with each other. We apply anisotropic tomography to 32,728 P‐wave travel time data of 479 teleseismic events recorded at 225 stations to study the 3‐D anisotropic Vp structure of the upper mantle beneath central‐east China. P‐wave radial anisotropy is investigated for the first time in the study region. Our results show that an obvious low‐velocity zone exists in the asthenosphere under the eastern part of our study region, which represents upwelling thermal flow from the Cathaysia block to the North China block (NCB) according to the results of azimuthal and radial anisotropies. A distinct high‐velocity zone with weak radial anisotropy exists under the middle Yangtze block, which is explained as the stable cratonic root. Two other weak high‐velocity zones appear near or within the mantle transition zone under the middle‐lower Yangtze River and the eastern NCB, which might be detached lithosphere or the stagnant Pacific slab. Combining with previous geological and geochemical results, we consider that both the NCB and the South China block have undergone a common geodynamic process in the Mesozoic due to their similar age trending of igneous rocks, which could be explained by a flat‐slab subduction model and a ridge subduction model. These two models are associated with the paleo‐Pacific plate subduction that might have played a key role in the evolution of eastern China.
Direct Measurements of the Malvinas Current Velocity Structure
Authors: Frey D. I. , Piola A. R. , Krechik V. A. , Fofanov D. V. , Morozov E. G. , Silvestrova K. P. , Tarakanov R. Yu. , Gladyshev S. V.
Published: March 2021

Direct velocity measurements of the Malvinas Current (MC) were carried out on multiple occupations of five transects across the flow using a Shipborne Acoustic Current Profiler (SADCP) on the R/V Akademik Sergey Vavilov and Akademik Mstislav Keldysh. These data are used to determine local features of the three‐dimensional velocity field of the current. The occupations covered the northern branch of the Antarctic Circumpolar Current (ACC) and the southern part of the MC. Five transects across the flow were located at 350–550 km from each other from the Drake Passage to the western Argentine Basin at 46°S. The new observations reveal that the current is organized in two branches, namely, an inshore branch extending to a depth of 200–300 m and a main offshore branch, which flows approximately over the 1,400 m isobath. This two‐branch structure is observed on each of the cross‐flow transects. The observed velocities of the inshore branch exceed 40 cm/s on each studied crossing of the current. The MC is a cold western boundary current that follows the Subantarctic Front. This flow originates as an offshoot of the northern branch of the ACC and continues over the Falkland/Malvinas Plateau and along the western slope of the Argentine Basin. Volume transports of the upper 700 m of the MC calculated for each crossing range between 1.4 and 4.4 Sv for the inshore branch and between 21.2 and 25.5 Sv for the offshore (main) branch.
Felsic Tesserae on Venus Permitted by Lithospheric Deformation Models
Authors: Resor P. G. , Gilmore M. S. , Straley B. , Senske D. A. , Herrick R. R.
Published: March 2021

Venus tessera terrain contains the oldest rocks preserved on the surface of the planet. The composition of the tesserae is unknown, but recent observations of near‐infrared emissivity from orbit suggest that they are silica rich. This contrasts with previous interpretation that silica‐rich rheologies are too weak to produce tessera folds. We examine the range of compositions consistent with the observed folds in the tessera. We map folds in Tellus Regio tessera using the highest resolution Magellan radar images (∼100 m) and stereo topography (∼1 km). We use fold spacings as input into a buckling analysis that simulates power law rheology using contemporary dry‐mineral flow laws and modeled igneous rock compositions, consistent with a predicted dry lithosphere for Venus in the recent era. The folds have dominant wavelengths of 6–19 km with amplitudes of 500–1,000 m, consistent with low strains (1%–12%). We confirm that observed folds require heat flows of ≥40 K/km and strain rates faster than 10−16s−1, higher than today. These low strain folds are unlikely to have significantly modified the preexisting tessera surface, thus older impact craters must have been removed by an earlier geologic process. We demonstrate that the folds can form in dry crust with a SiO2 content ranging from 48% to 72%. Dry felsic rheologies could explain low emissivity signatures of tesserae that are attributed to a low Fe2+. If felsic, tessera materials may have formed in a prior era via partial melting of hydrous materials derived from recycling of surface waters into the Venus mantle.
Late Miocene C4 Grassland Fire Feedbacks on the Indian Subcontinent
Authors: Karp Allison T. , Uno Kevin T. , Polissar Pratigya J. , Freeman Katherine H.
Published: March 2021

Fire dynamics potentially account for the asynchronous timing of the expansion of C4 grasslands throughout the Mio‐Pliocene world. Yet how fire, climate, and ecosystems interacted in different settings remain poorly constrained because it is difficult to quantify fires and fuel source over these timescales. Here, we apply molecular proxies for fire occurrence alongside records of vegetation change and paleohydrology in Bengal Fan sediments (ODP Leg 116) to examine fire feedbacks on the south Asian continent. We employ abundances of polycyclic aromatic hydrocarbons (PAHs) to reconstruct fire occurrence and δ13C measurements of pyrogenic PAHs to constrain fuel source and grassland burning. This combination allowed us to test whether: (1) a fire‐seasonality forcing facilitated the expansion of grassland ecosystems and (2) a fire‐C4 grass burning feedback maintained these systems. PAHs can be sourced from weathered fossil carbon (i.e., a petrogenic source) and from burned terrestrial biomass (i.e., a pyrogenic source). Alkylated and non‐alkylated structure abundance data distinguished pyrogenic from petrogenic sourced samples. A sharp increase in pyrogenic PAHs along with increases in δ2H and δ13C values of plant waxes at 7.4 Ma indicates increased fire coincided with the onset of C4 expansion and hydrologic change in South Asia. The correlated 13C enrichment in PAHs, 13C enrichment in plant waxes, and increased abundances of PAHs suggest burning of C4 grasslands likely maintained open ecosystems. Our results link fire to the initial opening of grassland ecosystems on a subcontinental‐scale and support disturbance as a critical mechanism of terrestrial biome transition.
Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia
Authors: Lundgren Sofie , Keränen Mikko A. I. , Kankainen Matti , Huuhtanen Jani , Walldin Gunilla , Kerr Cassandra M. , Clemente Michael , Ebeling Freja , Rajala Hanna , Brück Oscar , Lähdesmäki Harri , Hannula Sari , Hannunen Tiina , Ellonen Pekka , Young Neal S. , Ogawa Seishi , Maciejewski Jaroslaw P. , Hellström-Lindberg Eva , Mustjoki Satu
Published: March 2021

The prevalence and functional impact of somatic mutations in nonleukemic T cells is not well characterized, although clonal T-cell expansions are common. In immune-mediated aplastic anemia (AA), cytotoxic T-cell expansions are shown to participate in disease pathogenesis. We investigated the mutation profiles of T cells in AA by a custom panel of 2533 genes. We sequenced CD4+ and CD8+ T cells of 24 AA patients and compared the results to 20 healthy controls and whole-exome sequencing of 37 patients with AA. Somatic variants were common both in patients and healthy controls but enriched to AA patients’ CD8+ T cells, which accumulated most mutations on JAK-STAT and MAPK pathways. Mutation burden was associated with CD8+ T-cell clonality, assessed by T-cell receptor beta sequencing. To understand the effect of mutations, we performed single-cell sequencing of AA patients carrying STAT3 or other mutations in CD8+ T cells. STAT3 mutated clone was cytotoxic, clearly distinguishable from other CD8+ T cells, and attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells are common, associate with clonality, and can alter T-cell phenotype, warranting further investigation of their role in the pathogenesis of AA.
Adaptive immunity at the crossroads of autophagy and metabolism
Authors: Metur Shree Padma , Klionsky Daniel J.
Published: March 2021

The function of lymphocytes is dependent on their plasticity, particularly their adaptation to energy availability and environmental stress, and their protein synthesis machinery. Lymphocytes are constantly under metabolic stress, and macroautophagy/autophagy is the primary metabolic pathway that helps cells overcome stressors. The intrinsic role of autophagy in regulating the metabolism of adaptive immune cells has recently gained increasing attention. In this review, we summarize and discuss the versatile roles of autophagy in regulating cellular metabolism and the implications of autophagy for immune cell function and fate, especially for T and B lymphocytes.
Universal resilience patterns in labor markets
Authors: Moro Esteban , Frank Morgan R. , Pentland Alex , Rutherford Alex , Cebrian Manuel , Rahwan Iyad
Published: March 2021

Cities are the innovation centers of the US economy, but technological disruptions can exclude workers and inhibit a middle class. Therefore, urban policy must promote the jobs and skills that increase worker pay, create employment, and foster economic resilience. In this paper, we model labor market resilience with an ecologically-inspired job network constructed from the similarity of occupations’ skill requirements. This framework reveals that the economic resilience of cities is universally and uniquely determined by the connectivity within a city’s job network. US cities with greater job connectivity experienced lower unemployment during the Great Recession. Further, cities that increase their job connectivity see increasing wage bills, and workers of embedded occupations enjoy higher wages than their peers elsewhere. Finally, we show how job connectivity may clarify the augmenting and deleterious impact of automation in US cities. Policies that promote labor connectivity may grow labor markets and promote economic resilience.
Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer
Authors: Baca Sylvan C. , Takeda David Y. , Seo Ji-Heui , Hwang Justin , Ku Sheng Yu , Arafeh Rand , Arnoff Taylor , Agarwal Supreet , Bell Connor , O’Connor Edward , Qiu Xintao , Alaiwi Sarah Abou , Corona Rosario I. , Fonseca Marcos A. S. , Giambartolomei Claudia , Cejas Paloma , Lim Klothilda , He Monica , Sheahan Anjali , Nassar Amin , Berchuck Jacob E. , Brown Lisha , Nguyen Holly M. , Coleman Ilsa M. , Kaipainen Arja , De Sarkar Navonil , Nelson Peter S. , Morrissey Colm , Korthauer Keegan , Pomerantz Mark M. , Ellis Leigh , Pasaniuc Bogdan , Lawrenson Kate , Kelly Kathleen , Zoubeidi Amina , Hahn William C. , Beltran Himisha , Long Henry W. , Brown Myles , Corey Eva , Freedman Matthew L.
Published: March 2021

Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens. Here, we investigate the epigenomic basis of this resistance mechanism by profiling histone modifications in NEPC and PRAD patient-derived xenografts (PDXs) using chromatin immunoprecipitation and sequencing (ChIP-seq). We identify a vast network of cis-regulatory elements (N~15,000) that are recurrently activated in NEPC. The FOXA1 transcription factor (TF), which pioneers androgen receptor (AR) chromatin binding in the prostate epithelium, is reprogrammed to NE-specific regulatory elements in NEPC. Despite loss of dependence upon AR, NEPC maintains FOXA1 expression and requires FOXA1 for proliferation and expression of NE lineage-defining genes. Ectopic expression of the NE lineage TFs ASCL1 and NKX2-1 in PRAD cells reprograms FOXA1 to bind to NE regulatory elements and induces enhancer activity as evidenced by histone modifications at these sites. Our data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying cancer dependencies through epigenomic profiling.