bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for human diabetic cardiomyopathy
Authors: Marfella Raffaele , Sardu Celestino , Mansueto Gelsomina , Napoli Claudio , Paolisso Giuseppe
Published: March 2021

Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF.
Congruence and trajectories of device-measured and self-reported physical activity during therapy for early breast cancer
Authors: Helbrich H. , Braun M. , Hanusch C. , Mueller G. , Falk H. , Flondor R. , Harbeck N. , Hermelink K. , Wuerstlein R. , Keim S. , Neufeld F. , Steins-Loeber S. , Haertl K.
Published: March 2021

Purpose

This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments.

Methods

Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman’s Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance.

Results

Ninety-nine participants (median age = 50) were treated with adjuvant (N= 23), neoadjuvant (N= 21) or without chemotherapy (N= 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only “fair” (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p= 0.006, neoadjuvant: ∆ = 45min, p= 0.038) and lower in week 18 than in week 3 (∆ = 43min, p= 0.010).

Conclusion

Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.
Myocardial deformation in patients with a single left ventricle using 2D cardiovascular magnetic resonance feature tracking: a case–control study
Authors: Strodka Fabian , Logoteta Jana , Schuwerk Roman , Salehi Ravesh Mona , Gabbert Dominik Daniel , Uebing Anselm Sebastian , Krupickova Sylvia , Voges Inga
Published: March 2021

Ventricular dysfunction is a well-known complication in single ventricle patients in Fontan circulation. As studies exclusively examining patients with a single left ventricle (SLV) are sparse, we assessed left ventricular (LV) function in SLV patients by using 2D-cardiovascular magnetic resonance (CMR) feature tracking (2D-CMR-FT) and 2D-speckle tracking echocardiography (2D-STE). 54 SLV patients (11.4, 3.1–38.1 years) and 35 age-matched controls (12.3, 6.3–25.8 years) were included. LV global longitudinal, circumferential and radial strain (GLS, GCS, GRS) and strain rate (GLSR, GCSR, GRSR) were measured using 2D-CMR-FT. LV volumes, ejection fraction (LVEF) and mass were determined from short axis images. 2D-STE was applied in patients to measure peak systolic GLS and GLSR. In a subgroup analysis, we compared double inlet left ventricle (DILV) with tricuspid atresia (TA) patients. The population consisted of 19 DILV patients, 24 TA patients and 11 patients with diverse diagnoses. 52 patients were in NYHA class I and 2 patients were in class II. Most SLV patients had a normal systolic function but median LVEF in patients was lower compared to controls (55.6% vs. 61.2%, p = 0.0001). 2D-CMR-FT demonstrated reduced GLS, GCS and GCSR values in patients compared to controls. LVEF correlated with GS values in patients (p < 0.05). There was no significant difference between GLS values from 2D-CMR-FT and 2D-STE in the patient group. LVEF, LV volumes, GS and GSR (from 2D-CMR-FT) were not significantly different between DILV and TA patients. Although most SLV patients had a preserved EF derived by CMR, our results suggest that, LV deformation and function may behave differently in SLV patients compared to healthy subjects.
New methods for local vulnerability scenarios to heat stress to inform urban planning—case study City of Ludwigsburg/Germany
Authors: Birkmann Jörn , Sauter Holger , Garschagen Matthias , Fleischhauer Mark , Puntub Wiriya , Klose Charlotte , Burkhardt Albrecht , Göttsche Franziska , Laranjeira Kevin , Müller Julia , Büter Björn
Published: March 2021

Adaptation strategies to climate change need information about present and future climatic conditions. However, next to scenarios about the future climate, scenarios about future vulnerability are essential, since also changing societal conditions fundamentally determine adaptation needs. At the international and national level, first initiatives for developing vulnerability scenarios and so-called shared socioeconomic pathways (SSPs) have been undertaken. Most of these scenarios, however, do not provide sufficient information for local scenarios and local climate risk management. There is an urgent need to develop scenarios for vulnerability at the local scale in order to complement climate change scenarios. Heat stress is seen as a key challenge in cities in the context of climate change and further urban growth. Based on the research project ZURES (ZURES 2020 website), the paper presents a new method for human vulnerability scenarios to heat stress at the very local scale for growing medium-sized cities. In contrast to global models that outline future scenarios mostly with a country-level resolution, we show a new method on how to develop spatially specific scenario information for different districts within cities, starting from the planned urban development and expansion. The method provides a new opportunity to explore how different urban development strategies and housing policies influence future human exposure and vulnerability. Opportunities and constraints of the approach are revealed. Finally, we discuss how these scenarios can inform future urban development and risk management strategies and how these could complement more global or national approaches.
UVscope and its application aboard the ASTRI-Horn telescope
Authors: Maccarone Maria Concetta , La Rosa Giovanni , Catalano Osvaldo , Giarrusso Salvo , Segreto Alberto , Biondo Benedetto , Bruno Pietro , Gargano Carmelo , Grillo Alessandro , Impiombato Domenico , Russo Francesco , Sottile Giuseppe
Published: March 2021

UVscope is an instrument, based on a multi-pixel photon detector, developed to support experimental activities for high-energy astrophysics and cosmic ray research. The instrument, working in single photon counting mode, is designed to directly measure light flux in the wavelengths range 300-650 nm. The instrument can be used in a wide field of applications where the knowledge of the nocturnal environmental luminosity is required. Currently, one UVscope instrument is allocated onto the external structure of the ASTRI-Horn Cherenkov telescope devoted to the gamma-ray astronomy at very high energies. Being co-aligned with the ASTRI-Horn camera axis, UVscope can measure the diffuse emission of the night sky background simultaneously with the ASTRI-Horn camera, without any interference with the main telescope data taking procedures. UVscope is properly calibrated and it is used as an independent reference instrument for test and diagnostic of the novel ASTRI-Horn telescope.
Effective Neutrino Masses from Four Flavor Neutrino Mixing Matrix
Authors: Koranga Bipin Singh , Nautiyal Vivek Kumar
Published: March 2021

We consider the four neutrino oscillation that accommodate the all neutrino oscillation data. We consider the range of the corresponding mixing parameters by the result of neutrino oscillation experiments. Implicaion of the neutrino oscillation search for the neutrino mass square difference and mixing are discussed. We determine the possible values of the effective majorana neutrino mass$||=|{\sum }_{j}U_{ej}^{2}m_{j}|$||=|∑jUej2mj|in the four neutrino scenario. In the four-neutrino scheme there is an upper bound on |  | of the normal mass order is 2.0074eV forα= 0∘,β= 0∘andγ= 0∘. In the case of inverted mass order the upper bound on | < m > | is 2.0069eV forα= 0∘,β= 0∘andγ= 0∘.
The FMM accelerated PIES with the modified binary tree in solving potential problems for the domains with curvilinear boundaries
Authors: Kużelewski Andrzej , Zieniuk Eugeniusz
Published: March 2021

The paper presents an accelerating of solving potential boundary value problems (BVPs) with curvilinear boundaries by modified parametric integral equations system (PIES). The fast multipole method (FMM) known from the literature was included into modified PIES. To consider complex curvilinear shapes of a boundary, the modification of a binary tree used by the FMM is proposed. The FMM combined with the PIES, called the fast PIES, also allows a significant reduction of random access memory (RAM) utilization. Therefore, it is possible to solve complex engineering problems on a standard personal computer (PC). The proposed algorithm is based on the modified PIES and allows for obtaining accurate solutions of complex BVPs described by the curvilinear boundary at a reasonable time on the PC.
Ignoring Spatial and Spatiotemporal Dependence in the Disturbances Can Make Black Swans Appear Grey
Authors: Pace R. Kelley , Calabrese Raffaella
Published: March 2021

Automated valuation models (AVMs) are widely used by financial institutions to estimate the property value for a residential mortgage. The distribution of pricing errors obtained from AVMs generally show fat tails (Pender 2016; Demiroglu and JamesManagement Science, 64(4), 1747–1760 2018). The extreme events on the tails are usually known as “black swans” (Taleb 2010) in finance and their existence complicates financial risk management, assessment, and regulation. We show via theory, Monte Carlo experiments, and an empirical example that a direct relation exists between non-normality of the pricing errors and goodness-of-fit of the house pricing models. Specifically, we provide an empirical example using US housing prices where we demonstrate an almost perfect linear relation between the estimated degrees-of-freedom for a Student’stdistribution and the goodness-of-fit of sophisticated evaluation models with spatial and spatialtemporal dependence.
Rationality, preference satisfaction and anomalous intentions: why rational choice theory is not self-defeating
Authors: Fumagalli Roberto
Published: March 2021

The critics of rational choice theory (henceforth, RCT) frequently claim that RCT is self-defeating in the sense that agents who abide by RCT’s prescriptions are less successful in satisfying their preferences than they would be if they abided by some normative theory of choice other than RCT. In this paper, I combine insights from philosophy of action, philosophy of mind and the normative foundations of RCT to rebut this often-made criticism. I then explicate the implications of my thesis for the wider philosophical debate concerning the normativity of RCT for both ideal agents who can form and revise their intentions instantly without cognitive costs and real-life agents who have limited control over the formation and the dynamics of their own intentions.
Establishing Crosswalks Between Common Measures of Burnout in US Physicians
Authors: Brady Keri J. S. , Ni Pengsheng , Carlasare Lindsey , Shanafelt Tait D. , Sinsky Christine A. , Linzer Mark , Stillman Martin , Trockel Mickey T.
Published: March 2021

Background

Physician burnout is often assessed by healthcare organizations. Yet, scores from different burnout measures cannot currently be directly compared, limiting the interpretation of results across organizations or studies.

Objective

To link common measures of burnout to a single metric in psychometric analyses such that group-level scores from different assessments can be compared.

Design

Cross-sectional survey.

Setting

US practices.

Participants

A total of 1355 physicians sampled from the American Medical Association Physician Masterfile.

Main Measures

We linked the Stanford Professional Fulfillment Index (PFI) and Mini-Z Single-Item Burnout (MZSIB) scale to the Maslach Burnout Inventory (MBI) in item response theory (IRT) fixed-calibration and equipercentile analyses and created crosswalks mapping PFI and MZSIB scores to corresponding MBI scores. We evaluated the accuracy of the results by comparing physicians’ actual MBI scores to those predicted by linking and described the closest cut-point equivalencies across scales linked to the same MBI subscale using the resulting crosswalks.

Key Results

IRT linking produced the most accurate results and was used to create crosswalks mapping (1) PFI Work Exhaustion (PFI-WE) and MZSIB scores to MBI Emotional Exhaustion (MBI-EE) scores and (2) PFI Interpersonal Disengagement (PFI-ID) scores to MBI Depersonalization (MBI-DP) scores. The commonly used MBI-EE raw score cut-point of ≥27 corresponded most closely with respective PFI-WE and MZSIB raw score cut-points of ≥7 and ≥3. The commonly used MBI-DP raw score cut-point of ≥10 corresponded most closely with a PFI-ID raw score cut-point of ≥9.

Conclusions

Our findings allow healthcare organizations using the PFI or MZSIB to compare group-level scores to historical, regional, or national MBI scores (and vice-versa).
67863 Insulin use and depigmentation: a survey of real-world evidence
Authors: Lukasik James , Wintrob Zachary A.P. , Costin G. Emilia , Ceacareanu Alice C.
Published: March 2021

ABSTRACT IMPACT: Long-acting insulin containing protamine is more likely to be associated with skin depigmentation. OBJECTIVES/GOALS: An acquired disorder, skin depigmentation was found to be significantly correlated with diabetes. While a recent meta-analysis pointed at a possible similar pathogenesis, the possibility of vitiligo occurring as a drug-induced disease was never explored. This study aimed at elucidating whether utilization of specific insulins may play a role. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all injectable insulin users (n=8867). ICD-9/10 codes were abstracted from the medical conditions files for all the subjects reporting any type of injectable insulin use (1996-2017). Skin depigmentation codes identified in our dataset were 709 and L81. Insulins were categorized based on duration of action, short-acting (SA), intermediate-acting (IA), and long-acting (LA), as well as based on formulation ingredients (zinc, protamine-zinc, other), and insulin combination (SA with or without IA/LA containing or not protamine-zinc). The association between skin depigmentation occurrence and insulin type and/or category was assessed by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: A total of 225 out of 8867 individuals were diagnosed with skin depigmentation. Incidence of skin depigmentation was 2.25% in SA users (n1=3606, p=0.355), 2.24% in LA users (n2=3910, p=0.337), and 2.39% in IA users (n3=4015, p=0.062). Occurrence of skin depigmentation was similar between users of insulin mono- or combo therapy (p=0.758). Interestingly, among IA insulins, insulin protamine-zinc insulin (n4=3992) distinguished as being mainly responsible for the association with the occurrence of skin depigmentation (p=0.062), whereas insulin zinc was not (n5=37, p=1.000). The highest skin depigmentation incidence was observed among Pacific Islanders (2.66%, p=0.110). Males distinguished by a skin depigmentation incidence of 2.34% vs. 1.91% in females (p=0.086). DISCUSSION/SIGNIFICANCE OF FINDINGS: We report that presence of protamine-zinc may play a role in the development of skin depigmentation. It is uncertain whether this risk may be shared equally by insulin users diagnosed with type 1 and type 2 diabetes. Of note, we observed a higher skin depigmentation incidence than that reported by community- (0.2%) or hospital-based (1.8%) studies.
18075 Giving birth during COVID-19 from the birthing person’s perspective
Authors: Breman Rachel
Published: March 2021

ABSTRACT IMPACT: This work provides context from the patient perspective on the impact of hospital policies on their birthing experiencing during the first peak of the pandemic. OBJECTIVES/GOALS: The goal of this study was to report the intrapartum care experiences from people giving birth during the COVID-19 pandemic in the United States. Place of birth included hospital, birth center and home births. METHODS/STUDY POPULATION: Studies that involved patient-related data collection are hindered by pandemic-related changes in clinical practices and research policies. Our aim was to assess patient experience during a pandemic, we explored data collection via a large online community of pregnant women. We asked if women who birthed during COVID-19 changed their birth setting and if they experienced less respectful care, more pressure to undergo induction and/or cesarean birth and newborn separation. We also wanted to explore whether there were differences in the care experience depending on the race of the woman. Open ended questions on care experiences were included and content analysis conducted. Bivariate analysis was conducted comparing those from high versus less COVID-19 impacted areas and by race (White/Black self-identifying). RESULTS/ANTICIPATED RESULTS: The mean age was 31.5 years (SD = 5.0), 80.7% identified as White, 85.0% married, and 85.3% privately insured (N=388). Bivariate unadjusted analyses comparing high vs. low impact COVID-19 states, 22.3% considered changing their place of birth versus 12.7% in less impacted areas (p<.05): no difference pressure for induction/cesarean based on region. In bivariate unadjusted analysis comparing White and Black people, Black people had higher odds of pressure for cesarean or induction compared to White (OR 10.3, 95% CI 2.2 to 48.6, p=.0003). Black people had lower respect scores vs. White (68.7 vs. 72.3 p<.01) and higher odds of preterm birth 3.7 (1.1 to 12.4, p=0.04). Content analysis themes were institutional policies, changes in care, hospital staff interactions, sub-par care, support during birth and mental health. DISCUSSION/SIGNIFICANCE OF FINDINGS: The analysis demonstrated differences among participants from highly versus less impacted COVID-19 states. Disparities persisted with Black women reporting lower respect, pressure for interventions and more preterm birth when compared to White participants. Limitations include use of a convenience sample and self-reported data.
33392 Investigating the relationship between placement instability, mental health, behavioral and justice-related outcomes among sex-trafficked youth
Authors: Cook Mekeila , Rainock Meagan , Thomas Breanna
Published: March 2021

ABSTRACT IMPACT: This public health work contributes to the development and implementation of best practices for working with sex trafficked youth who experience placement instability and justice involvement. OBJECTIVES/GOALS: Youth removed from their home into foster care or a group home (i.e., placement instability) are vulnerable to sex trafficking. This study examines whether placement instability predicts mental health, behavioral and justice-related outcomes among sex-trafficked girls. METHODS/STUDY POPULATION: Placement instability occurs when children are temporarily or permanently removed from their home and placed in foster care or a group home. Domestic minor sex trafficking is exploitation and abuse of children for commercial sexual purposes in exchange for money or other goods/services. We hypothesize that sex trafficked girls who experience placement instability will report more mental health challenges, substance use, abuse history and justice involvement than those without placement instability. Data came from participant files in a specialty court program from 2012-2014 (N=184). Multiple sources contribute to the information contained court files; all data extracted by the research team come solely from the court files. Descriptive, bivariate, and logistic regression analyses were performed. RESULTS/ANTICIPATED RESULTS: All participants were (cis)female, 74% were African American, 96% US citizens, with average age of 16 years. Three-quarters of participants had a documented mental health challenge, such as depression and 88% reported substance use. Eighty-one percent of participants had been in a placement, with a group average of 4.5 placements. Girls with placement instability reported more mental health challenges (p<.001), substance use (p<.001), abuse (p<.001), running away (p<.001) and bench warrants (p<.001) than girls without placement instability. Logistic regression estimated housing instability was positively associated with mental health challenge, substance use, running away, number of bench warrants, and number of citations. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among girls who have been trafficked, placement instability places them at greater risk for personal and behavioral challenges, including increased justice involvement. Comprehensive trauma-informed services should be provided to the family to help mitigate issues in the home.
76352 Investigating the Association Between Intracerebral Hemorrhage (ICH) and Long-Term Encephalomalacia and Cortical Atrophy
Authors: Adapa Arjun , Khalsa Siri Sahib , Linzey Joseph , Pandey Aditya
Published: March 2021

ABSTRACT IMPACT: Investigating the relationship between ICH volume at presentation and cortical atrophy over time may help to explain the phenomenon of cognitive impairment after ICH. OBJECTIVES/GOALS: Non-traumatic intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. ICH causes both mechanical as well as oxidative injury leading to neurologic deterioration. However, the relationship between ICH volume and brain atrophy is not fully understood. To that end, we aimed to investigate this relationship. METHODS/STUDY POPULATION: A retrospective cohort of adult ICH patients over a 10-year study period were studied. Demographic data, ICH cause, location, laterality, and treatment, as well as other data, were collected. DICOM files of CT or MRI at presentation and all subsequent follow-up imaging up to 5-years post-ICH were obtained. Using a novel semi-automated image segmentation tool developed in MATLAB by our group, ICH volumes were segmented. Using T1w MRI data, ipsi- and contralateral brain volumes were segmented using NeuroQuant, a fully automated software for MRI volumetric processing, for both initial and follow-up MRIs. Ipsilateral and global cerebral volume changes over time were calculated using initial and follow-up MRI images. Spearman rank correlation between volume changes and ICH volumes were calculated for each patient. RESULTS/ANTICIPATED RESULTS: 75 spontaneous ICH patients with adequate imaging follow-up and both early and follow-up MRI comparisons were considered. Of these, 14 patients had MRIs adequate for segmentation by NeuroQuant. There was a positive correlation (R^2 = 0.72, p=0.03) between ABC/2, the traditional ICH volume measuring approach, and our semi-automatic segmentation tool, with ABC/2 tending to overestimate ICH volume. There was an average of -6.51% of total brain volume loss with respect to initial brain volume at follow-up. There was a negative correlation between ICH volume and both global (Spearman rank correlation coefficient (R)=-0.714, p=0.004)) and local atrophy (R=-0.785, p=0.0009), meaning that as ICH volume increases, there is greater brain volume loss. DISCUSSION/SIGNIFICANCE OF FINDINGS: Greater ICH volume is associated with greater brain volume loss both ipsilaterally, reflected as encephalomalacia, and globally. These findings are important as encephalomalacia can result in focal neurologic deficit and other neurological symptoms over time, while global brain atrophy is associated with dementia and cognitive decline.
79696 Reversible DNA Hypermethylation of the Interleukin-15 Promoter Induces IL-15 Expression, Drives the Pathogenesis of T-Cell Large Granular Lymphocytic Leukemia (T-LGLL) and Provides a Therapeutic Approach Using 5-Azacitidine
Authors: Brammer Jonathan E , Mishra Anjali , Boles Amy , Mansour Anthony , Mathe-Allainmat Monique , Quemener Agnes , Porcu Pierluigi
Published: March 2021

ABSTRACT IMPACT: This work describes, for the first time, the methylome in patients with T-LGLL, focusing on the IL-15 promoter, and clearly demonstrates that 5-azacytidine decreases IL-15 production leading to T-LGLL cell death. These results form the basis a translational clinical trial in T-LGLL that will begin accrual in 2021 OBJECTIVES/GOALS: T-LGLL is an incurable leukemia with few treatment options driven by overexpression of IL-15. Our objective is to characterize the methylation status of the IL-15 promoter in T-LGLL patients and evaluate the potential use of 5-azacytidine (5-aza) in a translational trial by studying the effect of 5-aza in vitro on IL-15 levels, and the IL-15 promoter. METHODS/STUDY POPULATION: We sorted T-LGLL patient (n=3) and normal donor (ND) samples (n=3) for CD3+/CD8+/CD5-/dim for T-LGLL immunophenotype. We analyzed DNA methylation and gene expression profiling using reduced representation bisulfite and RNA sequencing and determined differential methylation and gene expression using 1-way ANOVA analysis. To determine the functional significance of differential methylation, we evaluated MOTN-1 T-LGLL cell viability in vitro with 5-aza at increasing concentrations. Next, we evaluated IL-15 gene expression in MOTN-1 cells treated with 5-Aza versus MOTN-1 with control using western immunoblot. Finally, we exposed MOTN-1 cells to a novel IL-15 inhibitor, IBI-15, and compared cell viability against MOTN-1 cells exposed to an inactive control. RESULTS/ANTICIPATED RESULTS: There was significant differential methylation (P= 0.0178) and expression (P =0.0059) in T-LGLL patients vs ND. These data revealed significant differential hypermethylation of gene promoters, including an increase in DNA methylation of the IL-15 promoter in T-LGLL cells vs ND. In MOTN-1 cells treated in vitro with 5-Aza at 24 and 48 hours, a dose-dependent decrease in the viability of T-LGLL cells was observed, from 100% to 49.5%, p=0.037. Further, a marked decrease in IL-15 expression was observed at all concentrations of 5-aza compared to control (p=0.0001). Finally, a decrease in cell viability was observed utilizing the IL-15 inhibitor IBI-15 vs control. These results confirm that 5-aza leads to decreased transcription of the IL-15 gene, possibly due to hypomethylation of the IL-15 promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Hypermethylation of the IL-15 promoter and subsequent increase in IL-15 is critical to the pathogenesis of T-LGLL. Inhibition of the IL-15 promoter by 5-aza leads to down-regulation of the IL-15 gene transcript, which is sufficient to induce T-LGLL cell death. Based on these results, a phase I trial will be conducted using CC-486 (oral 5-Aza) in T-LGLL.
23154 Electrical stimulation of hippocampus and amygdala produces multiple distinct responses in human ventral temporal cortex
Authors: Huang Harvey , Gregg Nicholas M. , Ojeda Gabriela , Brinkmann Benjamin H. , Lundstrom Brian N. , Worrell Gregory A. , Miller Kai J. , Hermes Dora
Published: March 2021

ABSTRACT IMPACT: This study characterizes interactions between human limbic circuitry and ventral temporal cortex using single pulse electrical stimulation, which may inform emerging stimulation therapies for epilepsy. OBJECTIVES/GOALS: The goal of electrical brain stimulation treatment is to modulate brain network function. However, stimulation inputs to different brain sites alter the network in a variety of ways. This study examines that variability by characterizing responses in a target region while stimulating multiple other brain sites. METHODS/STUDY POPULATION: We measured voltages in intracranial EEG in 6 patients who had electrodes implanted for epilepsy monitoring. We stimulated pairs of electrodes at multiple sites in the brain with a single pulse every 5 to 7 s and measured the resulting corticocortical evoked potential (CCEP) responses in the ventral temporal cortex (VTC). Using a novel clustering method, we uncovered sets of distinct canonical response shapes from the 20 to 500 ms post-stimulation period. This allowed us to group stimulation sites that evoked similar responses. We then related each group to high frequency, broadband, changes in spectral power as a reflection of local neuronal activity. RESULTS/ANTICIPATED RESULTS: We found that the VTC receives strong inputs specifically from the amygdala and hippocampus, both in terms of amplitude and broadband spectral power change. However, inputs from the hippocampus produced a different canonical shape than those from the amygdala. We also observed that VTC responses to inputs from the insula clustered in shape with those from the amygdala. These clustering patterns were consistent across subjects, although the actual shapes of the clusters showed variability. We further observed that some shapes were more associated with increases in overall neuronal activity than others, as reflected by broadband spectral power change. DISCUSSION/SIGNIFICANCE OF FINDINGS: Stimulation of connected sites may drive excitability at the target region in ways that are described by sets of full-time-course responses. By capturing their shapes, we can begin to decipher canonical input types at the circuit level. This approach might identify how stimulation inputs can be tailored to therapy while mitigating adverse effects.
30143 Asymptomatic Thoracic Aortic Aneurysm Growth Rates and Predicting Factors: A Systematic Review and Meta-Analysis
Authors: Henry Matthew , Van Bakel Pieter , MacEachern Mark , Hoffman Bowman Marion , Eagle Kim , Patel Himanshu , Burris Nicholas
Published: March 2021

ABSTRACT IMPACT: Through conducting this systematic review and meta-analysis, we will elucidate which factors influence thoracic aortic aneurysm growth, which will further help clinicians to properly stratify and manage their patients with TAAs. OBJECTIVES/GOALS: Thoracic aortic aneurysms (TAA) are an indolent but fatal disease, and the patient characteristics that predict both overall growth and growth rate are still not well characterized. Our goal is to conduct a systematic review and meta-analysis in other to better describe different patient characteristics that predict TAA growth. METHODS/STUDY POPULATION: M.M. conducted a search of Ovid MEDLINE, Embase, and Scopus to identify articles. Inclusion criteria were any longitudinal study reporting asymptomatic TAA growth, growth rates, or clinical proxies for growth such as dissection, rupture, emergency surgery, and death. M.H and P.B. independently applied the criteria to the results of the search. Conflicts were resolved by N.B. Data was extracted and risk of bias assessed independently by M.H. and P.B. Summary estimates of the outcome variables are combined across studies using standard meta-analysis methods. Heterogeneity is assessed via forest plots, chi2 test (Q test), and I2 statistic. Sensitivity analysis is conducted to assess robustness of the findings. RESULTS/ANTICIPATED RESULTS: The literature search resulted in 3,419 abstracts, of which 176 were included and thus require a full text review. Cohen’s Kappa coefficient was 0.64, indicating substantial agreement and high inter-rater reliability. We describe four categories of patient characteristics influencing the growth of asymptomatic TAAs: demographics, genetic or inheritable conditions, hemodynamic or biomechanical factors, and serum biomarkers. We describe the measure of effect for all variables. We anticipate there is a significant level of heterogeneity between studies, and potentially moderate risk of bias for many of the included studies as they are retrospective and observational in nature. Furthermore, we anticipate publication bias and evaluate it with funnel plots. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding the factors that influence the growth of asymptomatic thoracic aortic aneurysms (TAA) is paramount, as the size and growth rate of TAAs dictates the clinical course. Little is understood about the degree to which different characteristics influence growth. This meta-analysis will help elucidate factors that promote TAA growth.
88462 Fluconazole distribution in CNS and gynecological tissues in HIV-related cryptococcal meningitis decedents
Authors: Nicol Melanie R. , Wang Fan , Richard Ambayo , Namuju Olivie Carolyne , Pastick Katelyn A , Boulware David R , Meya David B , Lukande Robert
Published: March 2021

ABSTRACT IMPACT: Plasma and CSF are not reliable estimates of drug exposure in tissue compartments relevant for treatment and prevention of infectious diseases. OBJECTIVES/GOALS: Globally, high dose fluconazole is widely used in the management of cryptococcal meningitis. While it is known to readily penetrate into cerebrospinal (CSF), less is known about drug concentrations in brain parenchymal tissues. Similarly, distribution of fluconazole into gynecological tissues has not been robustly characterized. METHODS/STUDY POPULATION: With informed consent from next-of-kin, we conducted autopsies within 24h of death for hospitalized Ugandans receiving fluconazole for treatment or secondary prophylaxis of cryptococcal meningitis. Dosing history was abstracted from medical chart and caregiver interviews. Fluconazole concentrations were determined using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) in plasma, CSF, 10 brain compartments (frontal, parietal, and occipital lobes, corpus callosum, globus pallidus, hippocampus, midbrain, medulla oblongata, spinal cord, and choroid plexus) and 4 female genital compartments (cervix, vagina, ovary, and uterus), depending on tissue availability. Descriptive statistics of tissue to plasma ratios were used to describe concentrations relative to plasma. RESULTS/ANTICIPATED RESULTS: Fluconazole concentrations were measured in available tissues of 21 individuals with detectable fluconazole in plasma. Daily doses of fluconazole were 200 mg (n=4), 400 mg (n=1), 800 mg (n=4), 1200 mg (n=9) or unknown (n=3). CSF concentrations (n=10) ranged from 93-1380% (median 100%) of plasma while brain concentrations (n=3) across all 10 compartments ranged from 45% to 89% (median 69%) of plasma. In the female genital tract, cervical concentrations (n=10) were 9-78% (median 65%) of plasma and in the 2 individuals with available tissue, concentrations in vaginal, ovarian, and uterine tissues were similar to cervix, ranging from 63-105% of plasma. DISCUSSION/SIGNIFICANCE OF FINDINGS: Measuring drug concentrations directly in tissues, the presumed site of action, improves estimates of drug efficacy. While fluconazole concentrations in CSF were similar to plasma, actual brain tissues were consistently lower. Concentrations were similar between upper and lower female genital tracts, but were consistently lower than plasma.
Complex multi-decadal ice dynamical change inland of marine-terminating glaciers on the Greenland Ice Sheet
Authors: Williams Joshua J. , Gourmelen Noel , Nienow Peter
Published: March 2021

Greenland's future contribution to sea-level rise is strongly dependent on the extent to which dynamic perturbations, originating at the margin, can drive increased ice flow within the ice-sheet interior. However, reported observations of ice dynamical change at distances >~50 km from the margin have a very low spatial and temporal resolution. Consequently, the likely response of the ice-sheet's interior to future oceanic and atmospheric warming is poorly constrained. Through combining GPS and satellite-image-derived ice velocity measurements, we measure multi-decadal (1993–1997 to 2014–2018) velocity change at 45 inland sites, encompassing all regions of the ice sheet. We observe an almost ubiquitous acceleration inland of tidewater glaciers in west Greenland, consistent with acceleration and retreat at glacier termini, suggesting that terminus perturbations have propagated considerable distances (>100 km) inland. In contrast, outside of Kangerlussuaq, we observe no acceleration inland of tidewater glaciers in east Greenland despite terminus retreat and near-terminus acceleration, and suggest propagation may be limited by the influence of basal topography and ice geometry. This pattern of inland dynamical change indicates that Greenland's future contribution to sea-level will be spatially complex and will depend on the capacity for dynamic changes at individual outlet glacier termini to propagate inland.
Genetic diversity in clustered colonies of an Antarctic marine mesopredator: a role for habitat quality?
Authors: Mori Emiliano , Brunetti Claudia , Carapelli Antonio , Burrini Lucia , Fattorini Niccolò , Ferretti Francesco , Olmastroni Silvia
Published: March 2021

Genetic structure may be highly variable across seabird species, and particularly among those that are distributed over large geographical areas. The Adélie penguin (Pygoscelis adeliae) is a numerically dominant Antarctic seabird that is considered to be a key species in coastal ecosystems. Since the Last Glacial Maximum, penguin colonization of the Antarctic coastline occurred at varying geographical and temporal scales, contributing to an incomplete understanding of how modern colonies relate to each other at local or regional scales. We assessed the population genetic structure of Adélie penguins (n= 86 individuals) from three adjacent colonies along the Victoria Land coast using molecular genetic markers (i.e. seven microsatellite loci isolated through next-generation sequencing). Our results indicate meta-population dynamics and possibly relationships with habitat quality. A generally low genetic diversity (Nei's index: 0.322–0.667) was observed within each colony, in contrast to significant genetic heterogeneity among colonies (pairwiseFST= 0.071–0.148), indicating that populations were genetically structured. Accordingly, an assignment test correctly placed individuals within the respective colonies from which they were sampled. The presence of inter-colony genetic differentiation contrasts with previous studies on this species that showed a lack of genetic structure, possibly due to higher juvenile or adult dispersal. Our sampled colonies were not panmictic and suggest a lower migration rate, which may reflect relatively stable environmental conditions in the Ross Sea compared to other regions of Antarctica, where the ocean climate is warming.
Surviving the Covid-19 Pandemic Lockdown: a Case Study
Authors: Kargbo Peter
Published: March 2021

In this article Peter Kargbo describes the impact of the first national lockdown, due to Covid-19, on students using the Hartley Library at the University of Southampton. He describes some of the ways that library services responded and looks at some aspects concerning collection development. He begins his article by taking a brief look at life in the library for students prior to the arrival of the pandemic before describing the period that followed up to the end of the academic year in summer 2020.
How to Get the Most Out of a Legal Technology Proof of Value
Authors: White Eleanor
Published: March 2021

Adoption of legal technology within law firms has seen a significant increase in recent years with the current necessity for seemingly indefinite remote working only adding to the need for technology solutions to keep legal workflows running. In light of this, legal technology purchases will undoubtedly see a further increase and a well conducted proof of value is crucial to making the right investment decision. This article is based on a talk given by Eleanor White at the BIALL Knowledge Management SIG in November 2018. It establishes the difference between a proof of concept and proof of value and elaborates on some key principles to consider during each phase of the latter. From the preparation and planning through to the running of the evaluation and the resulting decision-making process, this article addresses how to get the most out of the proof of value opportunity.
Quest for Data: Implementing an Enquiries Tracking System
Authors: Breslin Jas
Published: March 2021

Developing an enquiries tracking database can provide library services managers with data about how their services are being used and by whom. The software should to be configured to the requirements of the individual team in order to provide actionable data to help predict future needs and connect users with the right services. This article, written by Jas Breslin, follows one firm's journey to identify and roll-out a new research tracking system, Quest, under tight time constraints.
Covid-19: and the Impact on Print
Authors: Maher Michael
Published: March 2021

In this article Michael Maher writes about the declining print needs for law libraries within UK law firms in the context of the Covid-19 pandemic. The article begins by looking at the initial financial impact Covid-19 had across UK law firms. The second part of the article covers how home-working patterns have become the preferable option to working in the office. Finally, the author takes a change management approach, addressing what information professionals need to do to best manage and embed the change so as to continue to play a key part of the future, post-pandemic, law firm business.
A Low Signal Detection of X‐Rays From Uranus
Authors: Dunn W. R. , Ness J.‐U. , Lamy L. , Tremblay G. R. , Branduardi‐Raymont G. , Snios B. , Kraft R. P. , Yao Z. , Wibisono A. D.
Published: March 2021

Within the solar system, X‐ray emissions have been detected from every planet except the Ice Giants: Uranus and Neptune. We analyze the three archival Chandra X‐ray observations of Uranus (each 24–30 ks duration) to date: a stand‐alone Advanced CCD Imaging Spectrometer (ACIS) observation on August 7, 2002 and two High Resolution Camera (HRC) observations on November 11 and 12, 2017 coordinated with optical observations. For the earlier ACIS observation, the Uranus‐coincident photons were clustered in the 0.6–1.1 keV spectral range, consistent with emission from Jupiter and Saturn. To test the significance of the detected signal, we distributed a grid of ∼10,000 Uranus‐sized regions across the field of view (FoV). The number of Uranus‐coincident X‐ray photons in the 0.5–1.2 keV range exceeded 99.9% of Uranus‐sized regions across the FoV (10.2 standard deviations > FoV mean; probability of chance occurrence ∼10−6–10−7). However, the planetary signal was low with only 5 ± 2.2 X‐ray photons against a FoV mean background of 0.16 photons. Without the possibility of energy filtering, the recent HRC observations had a much brighter background (FoV mean ∼10 photons). Consequently, neither of the new observations provided a second unambiguous Uranus detection, although a 40‐min interval of brightening on November 12, 2017 did produce a signal above 99.9% of the FoV. The observed Uranus X‐ray fluxes of 10−15–10−16 erg/cm2/s are consistent with previous observational limits and modeling predictions. These fluxes exceed expectations from scattered solar emission alone, suggesting either a larger X‐ray albedo than Jupiter/Saturn or the possibility of additional X‐ray production processes at Uranus. Further observations are needed to test this.
The Role of Wind Stress in Driving the Along‐Shelf Flow in the Northwest Atlantic Ocean
Authors: Yang Jiayan , Chen Ke
Published: March 2021

The along‐shelf circulation in the Northwest Atlantic (NWA) Ocean is characterized by an equatorward flow from Greenland's south coast to Cape Hatters. The mean flow is considered to be primarily forced by freshwater discharges from rivers and glaciers while its variability is driven by both freshwater fluxes and wind stress. In this study, we hypothesize and test that the wind stress is important for the mean along‐shelf flow. A two‐layer model with realistic topography when forced by wind stress alone simulates a circulation system on the NWA shelves that is broadly consistent with that derived from observations, including an equatorward flow from Greenland coast to the Mid‐Atlantic Bight (MAB). The along‐shelf sea‐level gradient is close to a previous estimate based on observations. The along‐shelf flows exhibit strong seasonal variations with along‐shelf transports being strong in fall/winter and weak in spring/summer, consistent with available observations. It is found that the NWA shelf circulation is affected by both wind‐driven gyres through their western boundary currents and wind‐stress forcing on the shelf especially along the coasts of Newfoundland and Labrador. The local wind stress forcing has more direct impacts on flows in shallower waters along the coast while the open‐ocean gyres tend to affect the circulations along the outer shelf. Our conclusion is that wind stress is an important forcing of the main along‐shelf flows in the NWA. One objective of this study is to motivate further examination of whether wind stress is as important as freshwater forcing for the mean flow.
Tundra Underlain By Thawing Permafrost Persistently Emits Carbon to the Atmosphere Over 15 Years of Measurements
Authors: Schuur Edward A.G. , Bracho Rosvel , Celis Gerardo , Belshe E. Fay , Ebert Chris , Ledman Justin , Mauritz Marguerite , Pegoraro Elaine F. , Plaza César , Rodenhizer Heidi , Romanovsky Vladimir , Schädel Christina , Schirokauer David , Taylor Meghan , Vogel Jason G. , Webb Elizabeth E.
Published: March 2021

Warming of the Arctic can stimulate microbial decomposition and release of permafrost soil carbon (C) as greenhouse gases, and thus has the potential to influence climate change. At the same time, plant growth can be stimulated and offset C release. This study presents a 15‐year time series comprising chamber and eddy covariance measurements of net ecosystem C exchange in a tundra ecosystem in Alaska where permafrost has been degrading due to regional warming. The site was a carbon dioxide source to the atmosphere with a cumulative total loss of 781.6 g C m−2 over the study period. Both gross primary productivity (GPP) and ecosystem respiration (Reco) were already likely higher than historical levels such that increases in Reco losses overwhelmed GPP gains in most years. This shift to a net C source to the atmosphere likely started in the early 1990s when permafrost was observed to warm and thaw at the site. Shifts in the plant community occur more slowly and are likely to constrain future GPP increases as compared to more rapid shifts in the microbial community that contribute to increased Reco. Observed rates suggest that cumulative net soil C loss of 4.18–10.00 kg C m−2—8%–20% of the current active layer soil C pool—could occur from 2020 to the end of the century. This amount of permafrost C loss to the atmosphere represents a significant accelerating feedback to climate change if it were to occur at a similar magnitude across the permafrost region.