bluuebunny/crossref_metadata_2025 huggingface dataset:
3541 The association of corticosteroid use with inpatient mortality in acute exacerbation of idiopathic pulmonary fibrosis
Authors: Farrand Erica , Vittinghoff Eric , Ley Brett , Collard Harold
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Objective: To assess the impact of corticosteroid therapy on in-hospital mortality in IPF patients admitted with acute respiratory failure. METHODS/STUDY POPULATION: Methods: Patients with IPF were retrospectively identified in the University of California San Francisco medical center’s electronic health records from January 1, 2010 to June 1, 2018. Cases with IPF were defined as age 50 years or older, having at least two codes one month apart for idiopathic fibrosing alveolitis or post-inflammatory fibrosis (ICD-9 516.3, 516.31 or 515.0 or ICD-10 codes J84.9, J84.10, J84.111 or J84.112), and a subsequent hospitalization for acute respiratory failure or acute respiratory symptoms. The prevalence of pre-selected co-morbidities, clinical events (ICU admission, mechanical ventilation, lung transplantation) and clinical outcomes were assessed. A propensity score model for corticosteroid use was constructed using a multivariable logistic regression with inclusion of corticosteroid-associated demographic and baseline variables (univariate p-value < 0.25). A marginal structural model (MSM) was used to address time-dependent confounding and mediating effects of ICU admission and mechanical ventilation by applying inverse probability weighting for receipt of corticosteroid treatment. Secondary outcome analysis was performed on patients who survived hospital admission. RESULTS/ANTICIPATED RESULTS: Results: A total of 132 patients with IPF and an acute respiratory admission were identified. 48 patients (36%) received corticosteroids during their admission. Applying inverse weighting to time-dependent co-variates (ICU admission and invasive mechanical ventilation) in a MSM, corticosteroid therapy was not associated with risk of in-hospital mortality (odds ratio 1.82; 95% CI, 0.47-6.99; p = 0.39). After adjusting for corticosteroid therapy using a propensity score, corticosteroid therapy remained unassociated with in-hospital mortality (odds ratio 1.53, 95% confidence interval [CI] 0.37, 6.29; p = 0.55). There was no difference in discharge disposition or time to hospital readmission by corticosteroid treatment. There was a possible increase in time to death following discharge in patients receiving corticosteroids (Figure). DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: This study suggests that treatment of acute exacerbations of interstitial lung disease with corticosteroids does not improve short-term outcomes, including in-hospital mortality, all-cause non-elective re-hospitalization or death within 6 months of discharge. Further research in larger cohorts is needed to more definitively assess this relationship.
3234 Cell Proliferation and Differentiation in 3D printed Polycarbonate Urethane Porous Scaffolds
Authors: Abar Bijan , Aalleja Alejandro , Kelly Cambre , Windheim Natalia Von , West Jennifer , Gall Kenneth
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to understand how porosity and collagen filling impact cell proliferation and differentiation in 3D printed scaffolds. METHODS/STUDY POPULATION: 3 groups of scaffolds will be 3D printed using FDM: solid scaffold, porous scaffold and porous scaffold with collagen gel (n=10 for each group) Internal geometries and surface structure will be analyzed using micro CT and Scanning Electron Mi RESULTS/ANTICIPATED RESULTS: We hypothesize that porosity and collagen filler will increase signal from Picogreen assay and ALP assay when normalized to scaffold surface area, indicating enhanced cell proliferation and differentiation. DISCUSSION/SIGNIFICANCE OF IMPACT: 3D printing PCU is a relatively new technique with very little published in the literature. Previous work has focused on the mechanical properties and not the biological response to the polymer. Understanding how to optimize cellular proliferation and differentiation can lead to the development of better implants that will integrate into the host’s structure and facilitate tissue regeneration.
3211 Place, Poverty, and Prevention: A Mixed Methods Study
Authors: Kurani Shaheen , Shah Nilay , Lampman Michelle
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Understand the association between ADI and completion of preventative cancer screening and high risk behaviors -Identify how to operationalize ADI in clinical settings to assist care teams and improve overall care delivery. METHODS/STUDY POPULATION: Aim 1: Paneled Mayo Clinic patients living in MN, IA, or WI Aim 2: BRFSS survey respondents from MN, IA, or WI Aim. 3: Community health officials and Mayo Clinic care teams. RESULTS/ANTICIPATED RESULTS: We anticipate that areas with greater composite deprivation will have lower completion rates of cancer screening and higher risk behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: No single body of work has illustrated how ADI relates to completion of preventative cancer screening and high-risk behaviors. Due to the limited research focused on area deprivation and behavioral health, our work will identify some of the first national hot spots with high deprivation and high-risk behaviors. Additionally, this is one of the first studies describing spatial variation in health outcomes for Mayo Clinic patients. Understanding the association between ADI and patient adherence to preventative screening will allow us to support care teams in providing personalized and sustainable care for patients living in areas of high deprivation. The strength and novelty of this project is in the utility of the mixed methods design, which provides a more complete understanding of geographic disparities and a unique perspective to patient care, a perspective that is not portrayed in existing literature.
3365 Treatment Interruptions and Early Discontinuation of Hormone Therapy in Hormone Receptor-Positive Breast Cancer Patients
Authors: Mao Daqin , Chang Hong , Rodday Angie Mae , Hachem Hilal , Erban John K. , Freund Karen , Parsons Susan
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.
3397 Genetic variants in gestational diabetes mellitus
Authors: Kothiyal Prachi , Lawrence Grace , Godinez Irma , Huddleston Kathi Chesnutt , Fuller Alma , Hazrati Sahel , Wong Wendy , Deeken John , Niederhuber John
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: This study aims to identify genetic biomarkers of GDM and facilitate the understanding of its molecular underpinnings. METHODS/STUDY POPULATION: We identified a cohort of mothers diagnosed with GDM in our longitudinal birth study by mining Electronic Health Records of participants utilizing PheCode map with ICD-9 and ICD-10 codes. We verified each case using ACOG’s GDM diagnosis criteria. RESULTS/ANTICIPATED RESULTS: Whole genome sequencing (WGS) data were available for 111 confirmed cases (out of 205) and 706 controls (out of 1,429) from different ancestries (412 EUR, 256 AMR, 56 EAS, 26 SAS and 18 AFR; 49 OTHER). SAS had the highest incidence of GDM at 38.46% and EUR had the lowest at 6.55%. We performed logistic regression using computed ancestry, age and BMI as covariates to determine if any variants are associated with GDM. The top variant (rs139014401) was found in an intron of DFFB gene, which is p53-bound and regulates DNA fragmentation during apoptosis. We will investigate the robustness of 49 identified variants and will separate the cohort by ancestry to detect population-specific differences in the top loci. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of molecular biomarkers in GDM across different ancestral backgrounds will address a gap in current GDM research. Findings may enhance screening and enable clinicians to identify those at risk for developing GDM earlier in the pregnancy. Early management of mothers at risk may lead to better health outcomes for mother and baby.
3488 A comparison between the Rolling 6 and 3+3 dose escalation study designs for phase 1 clinical trials
Authors: Minard Charles Gene , Rau Rachel , Hilsenbeck Susan , Weigel Brenda J. , Fox Elizabeth , Adamson Peter , Blaney Susan
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.
Resolvent-analysis-based design of airfoil separation control
Authors: Yeh Chi-An , Taira Kunihiko
Published: March 2019

We use resolvent analysis to design active control techniques for separated flows over a NACA 0012 airfoil. Spanwise-periodic flows over the airfoil at a chord-based Reynolds number of$23\,000$and a free-stream Mach number of$0.3$are considered at two post-stall angles of attack of$6^{\circ }$and$9^{\circ }$. Near the leading edge, localized unsteady thermal actuation is introduced in an open-loop manner with two tunable parameters of actuation frequency and spanwise wavelength. To provide physics-based guidance for the effective choice of these control input parameters, we conduct global resolvent analysis on the baseline turbulent mean flows to identify the actuation frequency and wavenumber that provide large perturbation energy amplification. The present analysis also considers the use of a temporal filter to limit the time horizon for assessing the energy amplification to extend resolvent analysis to unstable base flows. We incorporate the amplification and response mode from resolvent analysis to provide a metric that quantifies momentum mixing associated with the modal structure. This metric is compared to the results from a large number of three-dimensional large-eddy simulations of open-loop controlled flows. With the agreement between the resolvent-based metric and the enhancement of aerodynamic performance found through large-eddy simulations, we demonstrate that resolvent analysis can predict the effective range of actuation frequency as well as the global response to the actuation input. We believe that the present resolvent-based approach provides a promising path towards mean flow modification by capitalizing on the dominant modal mixing.
Decay of turbulence in a liquid metal duct flow with transverse magnetic field
Authors: Zikanov Oleg , Krasnov Dmitry , Boeck Thomas , Sukoriansky Semion
Published: March 2019

Decay of honeycomb-generated turbulence in a duct with a static transverse magnetic field is studied via direct numerical simulations. The simulations follow the revealing experimental study of Sukoriansky et al. (Exp. Fluids, vol. 4 (1), 1986, pp. 11–16), in particular the paradoxical observation of high-amplitude velocity fluctuations, which exist in the downstream portion of the flow when the strong transverse magnetic field is imposed in the entire duct including the honeycomb exit, but not in other configurations. It is shown that the fluctuations are caused by the large-scale quasi-two-dimensional structures forming in the flow at the initial stages of the decay and surviving the magnetic suppression. Statistical turbulence properties, such as the energy decay curves, two-point correlations and typical length scales are computed. The study demonstrates that turbulence decay in the presence of a magnetic field is a complex phenomenon critically depending on the state of the flow at the moment the field is introduced.
Who Was Afraid of Pregnancy Tests? Gestational Information and Reproduction Policies in France (1920–50)
Authors: Cahen Fabrice
Published: March 2019

Though resulting from a long-term process, the need to manage pregnancies both medically and bureaucratically became a state concern, especially from the 1920s onwards. A woman’s official obligation to notify the state of her pregnancy (and therefore to know it on time) goes beyond a matter of biopolicies and poses a range of contradictions. ‘Pregnant or not?’ – as an issue of knowledge – is a powerful tool for apprehending the tensions between individual freedom, privacy, institutional requirements and professional powers.

In order to better understand the historical meaning of pregnancy diagnostics in mid-twentieth-century France, this paper combines three dimensions: uncertainty and its management; the informational asymmetry between institutional agents and women; and the diachronic dimension of gestation. Writing this history sheds more light on an apparent paradox: while knowing and notifying one’s own pregnancy became a duty, the tools that could help women eliminate some doubt right from the first months of their pregnancy – in particular the innovation of laboratory diagnosis – was seen as a danger. When, in 1938, private laboratories began publishing advertisements for the laboratory test in the most widely-read newspapers, tending to reframe it as a commercial service, the anti-abortion crusade was increasing its propaganda and its political pressure. This crusade’s legal victory proved incomplete, but for a long time some of the most conservative physicians recommended great parsimony in prescribing testing. Combined with reducing the legal time limit for notification, this conflict shows how the state injunctions towards women could look like a ‘double bind’.
Looking into the Test Tube: The Birth of IVF on British Television
Authors: Dow Katharine
Published: March 2019

The birth of Louise Brown, the world’s first ‘test-tube baby’, has come to signify the moment at which technologically assisted human reproduction became a re ality. This was a highly mediated and visible reality, as this article explores through the example of a British television documentary about Louise Brown broadcast when she was just six weeks old, ‘To Mrs Brown… A Daughter’ (Thames Television, 1978). In the article, I discuss the programme alongside data from an interview with its producer, Peter Williams. Williams sought to convince the public that IVF was morally acceptable and to cultivate sympathy for the infertile through this film. I will consider how he went about this by focusing on the programme’s visual presentation of Louise Brown, Peter Williams’ aims in making the film and his sympathetic relationship with the ‘pioneers’ of IVF, gynaecologist Patrick Steptoe and physiologist Robert Edwards. I will conclude with a discussion of the political implications of this film and how it contributed to the normalisation of IVF at a pivotal moment in its history.
Irreverent Reading: Humor, Erudition and Subalternity in the fiction of Bankim Chandra Chattopadhyay and Fakir Mohan Senapati
Authors: Mahapatra Aruni
Published: March 2019

This essay examines scenes from prose fiction in which two Indian novelists (Bankim Chandra Chatterjee and Fakir Mohan Senapati) interrogated subalternity in colonial India by talking about books. It first examines narrators’ frustration with books as acts of “irreverent reading” in colonial India, where the presence and scarcity of readable print produced anxieties about language and community. It then examines “reading” in the novels and compares how different kinds of irreverence allows narrators to introduce women characters as agents of very different kinds of violence in colonial India. Following insights of Gayatri Spivak, Elleke Boehmer, and Leah Price, and others, this article argues that Fakir Mohan Senapati’s sensitivity to his readers’ inability to access books enabled his novel to empower readers without books and emphasize how community in colonial India was constituted by the collective forgetting of women.
Binti’s R/evolutionary Cosmopolitan Ecologies
Authors: Crowley Dustin
Published: March 2019

Okorafor’s Binti series consistently blurs the lines between human and other-than-human, between technological and natural/spiritual, between local and global in ways that refuse to extract or abstract humans from their entanglements with environments and others, writ large and small. Set in a post–climate change Africa embroiled in regional and interstellar conflict, the narratives’ cosmopolitics are unrelentingly ecological, involving nonhuman participants and embedded in material particularities that shape conflicts and relations; at the same time, the ecology is always cosmopolitan, with those nonhuman actors exercising agency within complex worlds of difference that cross over and connect cosmos, polis, and oikos. Contrary to the sometimes-utopic connotation of both cosmopolitanism and ecology, however, such difference is neither subsumed to a harmonious whole, nor held in benign relativism. Rather, Binti depicts multispecies agency that is always in dynamic tension, driving r/evolutionary growth in posthuman relations and in the genres through which we imagine them.
Conflict, Peace, and the Evolution of Women's Empowerment
Authors: Webster Kaitlyn , Chen Chong , Beardsley Kyle
Published: March 2019

How do periods of conflict and peace shape women's empowerment around the world? While existing studies have demonstrated that gender inequalities contribute to the propensity for armed conflict, we consider how the anticipation and realization of armed conflict shape women's opportunities for influence in society. Some scholars have pointed to the role that militarization and threat play in entrenching male dominance, while others have argued that periods of warfare can upend existing gender hierarchical orders. We posit mechanisms by which the preparation for and experiences during war affect change in women's empowerment. We develop and test observable implications using cross-national data from 1900 to 2015. We find that, at least in the short and medium term, warfare can disrupt social institutions and lead to an increase in women's empowerment via mechanisms related to role shifts across society and political shifts catalyzed by war. Reforming institutions and mainstreaming gender during peace processes stand to have important legacies for gender power relations in postconflict societies, though much more may be needed for more permanent change.
Convicts, Commodities, and Connections in British Asia and the Indian Ocean, 1789–1866
Authors: Anderson Clare
Published: March 2019

This article explores the transportation of Indian convicts to the port cities of the Bay of Bengal and the Indian Ocean during the period 1789 to 1866. It considers the relationship between East India Company transportation and earlier and concurrent British Crown transportation to the Americas and Australia. It is concerned in particular with the interconnection between convictism and enslavement in the Atlantic and Indian Ocean worlds. Examining the roots of transportation in South Asia in the repressive policies of the East India Company, especially in relation to its occupation of land and expropriation of resources, it moves on to discuss aspects of convicts’ lives in Moulmein, Singapore, Mauritius, and Aden. This includes their labour regime and their relationship to other workers. It argues that Indian convict transportation was part of a carceral circuit of repression and coerced labour extraction that was intertwined with the expansion of East India Company governance and trade. The Company used transportation as a means of removing resistant subjects from their homes, and of supplying an unfree labour force to develop commodity exports and to build the infrastructure necessary for the establishment, population, and connection of littoral nodes. However, the close confinement and association of convicts during transportation rendered the punishment a vector for the development of transregional political solidarities, centred in and around the Company's port cities.
The Legislature at War: Bandits, Runaways and the Emergence of a Virginia Doctrine of Separation of Powers
Authors: Steilen Matthew
Published: March 2019

The politics of war severely divided the Virginia Southside during the American Revolution. Laborers, ship pilots and other landless men and women bitterly resented the efforts of the patriot gentry to stop trade with Great Britain and to establish a military force. Planters feared that the presence of the British Navy would encourage slaves to flee or attack their masters. What role did law play in the patriot response to these conditions? This essay uses the case of Josiah Philips, who led a banditti residing in the Great Dismal Swamp, to show how law intersected with class and race in patriot thinking. The gentry's view of the landless as dependent and lacking in self-control and its view of black slaves as posing a constant threat of violence supported the application of special legal regimes suited to these dangers. In particular, Philips was “attainted” by the General Assembly, a summary legislative legal proceeding traditionally employed against offenders who threatened government itself. While the attainder was uncontroversial when it passed, the significance of the Assembly's intervention changed over time. By the late 1780s, some among the state's legal elite regarded the Assembly as having unnecessarily interfered in the ordinary course of justice, which they were then seeking to reform. This opened the way to recharacterize the Assembly's extraordinary legal jurisdiction as an arbitrary exercise of lawmaking power.
A general proof certification framework for modal logic
Authors: LIBAL TOMER , VOLPE MARCO
Published: March 2019

One of the main issues in proof certification is that different theorem provers, even when designed for the same logic, tend to use different proof formalisms and produce outputs in different formats. The project ProofCert promotes the usage of a common specification language and of a small and trusted kernel in order to check proofs coming from different sources and for different logics. By relying on that idea and by using a classical focused sequent calculus as a kernel, we propose here a general framework for checking modal proofs. We present the implementation of the framework in a Prolog-like language and show how it is possible to specialize it in a simple and modular way in order to cover different proof formalisms, such as labelled systems, tableaux, sequent calculi and nested sequent calculi. We illustrate the method for the logicKby providing several examples and discuss how to further extend the approach.
PHYLOGENY OF TWO AFRICAN GENERA OF SAPOTACEAE – ENGLEROPHYTUM AND SYNSEPALUM
Authors: Borg D. , Richardson J. E. , Harris D. J. , Gautier L. , Hughes M. , Mackinder B.
Published: March 2019

Englerophytum and Synsepalum are two closely related genera of trees and shrubs from the African tropics. Previous molecular studies have shown that these genera collectively form a clade within the subfamily Chrysophylloideae (Sapotaceae). However, little is known about the inter-relationships of the taxa within the Englerophytum–Synsepalum clade. In this study, nuclear ribosomal DNA and plastid trnH–psbA sequences were used to estimate the phylogeny within the clade. Results indicate that the clade consists of six major lineages, two composed solely of taxa from the genus Englerophytum and four composed of taxa from the genus Synsepalum. Each lineage can be distinguished by suites of vegetative and floral characters. Leaf venation patterns, calyx fusion, style length and staminodal structure were among the most useful characters for distinguishing clades. Some of the subclades within the Englerophytum–Synsepalum clade were also found to closely fit descriptions of former genera, most of which were described by Aubréville, that have since been placed in synonymy with Englerophytum and Synsepalum. The clade with the type species of Englerophytum also contains the type species of the genera Wildemaniodoxa and Zeyherella, which are confirmed as synonyms.
A qualitative study to explore fathers’ attitudes towards breastfeeding in South West England
Authors: Merritt Rowena , Vogel Michelle , Ladbury Patrick , Johnson Sally
Published: March 2019

Aim

To explore the beliefs, attitudes, and behaviours of fathers towards breastfeeding and how they impact either positively or negatively on their partners’ decisions to initiate or continue breastfeeding.

Background

Despite policy initiatives at a national and international level and the increased number of baby-friendly hospitals within the UK, breastfeeding rates are slow to rise. Support from both parents has been proven to increase uptake and continuation rates, but there is little research into the emotional experience of fathers when it comes to breastfeeding.

Methods

We conducted qualitative interviews with 18 fathers in Wiltshire, England. Principles of grounded theory were used throughout this study to guide the sampling, data collection, and data analysis.

Findings

Fathers knew the health benefits of breastfeeding and wanted their child to breastfeed but were unsure of their place in the feeding process because they felt it was not their body. While they were aware of the benefits of breast milk for infants, fathers felt less informed of the practicalities of breastfeeding and the potential challenges they and their partner might have to overcome to breastfeed successfully for the recommended six-month period. Based on these findings, three segments were identified: the problem bonders, the dual bonders, and the pragmatists. All segments were concerned with the well-being of their partner and child and wanted their child to be breastfed. Health professionals can use the results of this study to create prenatal educational resources that take more of a preventive and problem-solving approach as opposed to promoting breastfeeding in efforts to comply with National Health Service guidelines, without offering solutions to common breastfeeding problems.
The right to food, why US ratification matters
Authors: Riches Graham
Published: March 2019

Molly Anderson's argument that irrespective of the US refusal to ratify the International Covenant on Economic, Social and Cultural Rights (ICESCR, 1966) it is time for federal food assistance programs such as SNAP mandated through the Farm Bill to adopt a right to food and nutrition approach is foresighted and significant. As is Anne Bellow's succinct and equally powerful proposal for widening the debate to include a system's-based human rights approach to a National Food Plan. Their timely advocacy is compelling given the few influential US food policy voices speaking from a food justice perspective about the dysfunctional industrial food system and the failure of the Federal Government to ensure access to healthy food and food security for all.
The Coastal Ocean Circulation Influence on the 2018 West Florida Shelf K. brevis Red Tide Bloom
Authors: Weisberg Robert H. , Liu Yonggang , Lembke Chad , Hu Chuanmin , Hubbard Katherine , Garrett Mathew
Published: March 2019

Blooms of the harmful alga, Karenia brevis on the west Florida continental shelf are thought to initiate offshore before manifesting as a nuisance along the coastline. Contributing to such blooms are a complex sequence of events occurring within oligotrophic waters, which in any given year may or may not be facilitated by the ocean circulation. Once initiation occurs, the delivery from the region of offshore origination to the region of coastline manifestation requires an upwelling circulation, whereby K. brevis cells are advected shoreward along the bottom. The 2018 K. brevis bloom was particularly intense owing to cells from the preceding 2017 bloom being reinforced by a newly formed bloom in 2018, a year when the offshore conditions in spring through early summer were again favorable for bloom development. As an event response to determine the potential for new cells to be delivered to the shore, a glider was deployed from 24 August 2018 to 17 September 2018 with a track line designed to map water properties over the hypothesized initiation region. The coastal ocean circulation during the deployment interval was generally upwelling favorable, but the passage of Tropical Storm Gordon temporarily disrupted this flow, after which K. brevis appeared along the Florida Panhandle coast. Strong upwelling then reestablished and K. brevis was subsequently observed along Florida's east coast. We describe the glider deployment, the K. brevis observations, and we use a numerical circulation model to account for the K. brevis manifestation as occurred along Florida's west, Panhandle, and east coasts.
Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer
Authors: Formisano Luigi , Lu Yao , Servetto Alberto , Hanker Ariella B. , Jansen Valerie M. , Bauer Joshua A. , Sudhan Dhivya R. , Guerrero-Zotano Angel L. , Croessmann Sarah , Guo Yan , Ericsson Paula Gonzalez , Lee Kyung-min , Nixon Mellissa J. , Schwarz Luis J. , Sanders Melinda E. , Dugger Teresa C. , Cruz Marcelo Rocha , Behdad Amir , Cristofanilli Massimo , Bardia Aditya , O’Shaughnessy Joyce , Nagy Rebecca J. , Lanman Richard B. , Solovieff Nadia , He Wei , Miller Michelle , Su Fei , Shyr Yu , Mayer Ingrid A. , Balko Justin M. , Arteaga Carlos L.
Published: March 2019

Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists.
Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design
Authors: Lu Xiaoyun , Liu Yuwan , Yang Yiqun , Wang Shanshan , Wang Qian , Wang Xiya , Yan Zhihui , Cheng Jian , Liu Cui , Yang Xue , Luo Hao , Yang Sheng , Gou Junran , Ye Luzhen , Lu Lina , Zhang Zhidan , Guo Yu , Nie Yan , Lin Jianping , Li Sheng , Tian Chaoguang , Cai Tao , Zhuo Bingzhao , Ma Hongwu , Wang Wen , Ma Yanhe , Liu Yongjun , Li Yin , Jiang Huifeng
Published: March 2019

Acetyl-CoA is a fundamental metabolite for all life on Earth, and is also a key starting point for the biosynthesis of a variety of industrial chemicals and natural products. Here we design and construct a Synthetic Acetyl-CoA (SACA) pathway by repurposing glycolaldehyde synthase and acetyl-phosphate synthase. First, we design and engineer glycolaldehyde synthase to improve catalytic activity more than 70-fold, to condense two molecules of formaldehyde into one glycolaldehyde. Second, we repurpose a phosphoketolase to convert glycolaldehyde into acetyl-phosphate. We demonstrated the feasibility of the SACA pathway in vitro, achieving a carbon yield ~50%, and confirmed the SACA pathway by 13C-labeled metabolites. Finally, the SACA pathway was verified by cell growth using glycolaldehyde, formaldehyde and methanol as supplemental carbon source. The SACA pathway is proved to be the shortest, ATP-independent, carbon-conserving and oxygen-insensitive pathway for acetyl-CoA biosynthesis, opening possibilities for producing acetyl-CoA-derived chemicals from one-carbon resources in the future.
Eutrophication will increase methane emissions from lakes and impoundments during the 21st century
Authors: Beaulieu Jake J. , DelSontro Tonya , Downing John A.
Published: March 2019

Lakes and impoundments are an important source of methane (CH4), a potent greenhouse gas, to the atmosphere. A recent analysis shows aquatic productivity (i.e., eutrophication) is an important driver of CH4 emissions from lentic waters. Considering that aquatic productivity will increase over the next century due to climate change and a growing human population, a concomitant increase in aquatic CH4 emissions may occur. We simulate the eutrophication of lentic waters under scenarios of future nutrient loading to inland waters and show that enhanced eutrophication of lakes and impoundments will substantially increase CH4 emissions from these systems (+30–90%) over the next century. This increased CH4 emission has an atmospheric impact of 1.7–2.6 Pg C-CO2-eq y−1, which is equivalent to 18–33% of annual CO2 emissions from burning fossil fuels. Thus, it is not only important to limit eutrophication to preserve fragile water supplies, but also to avoid acceleration of climate change.
Assessing the Policy gaps for achieving China’s climate targets in the Paris Agreement
Authors: Gallagher Kelly Sims , Zhang Fang , Orvis Robbie , Rissman Jeffrey , Liu Qiang
Published: March 2019

China committed to peak its carbon emissions around 2030, with best efforts to peak early, and also to achieve 20% non-fossil energy as a proportion of primary energy supply by 2030. These commitments were included in China’s nationally-determined contribution to the 2015 Paris Agreement on climate change. We develop and apply a mixed-method methodology for analyzing the likelihood of current Chinese policies reducing greenhouse gas emissions in accordance with China’s Paris commitments. We find that China is likely to peak its emissions well in advance of 2030 and achieve its non-fossil target conditional on full and effective implementation of all current policies, successful conclusion of power-sector reform, and full implementation of a national emissions-trading system (ETS) for the power and additional major industrial sectors after 2020. Several policy gaps are identified and discussed.
Water impacts nutrient dose responses genome-wide to affect crop production
Authors: Swift Joseph , Adame Mark , Tranchina Daniel , Henry Amelia , Coruzzi Gloria M.
Published: March 2019

Changes in nutrient dose have dramatic effects on gene expression and development. One outstanding question is whether organisms respond to changes in absolute nutrient amount (moles) vs. its concentration in water (molarity). This question is particularly relevant to plants, as soil drying can alter nutrient concentration, without changing its absolute amount. To compare the effects of amount vs. concentration, we expose rice to a factorial matrix varying the dose of nitrogen (N) and water (W) over a range of combinations, and quantify transcriptome and phenotype responses. Using linear models, we identify distinct dose responses to either N-moles, W-volume, N-molarity (N/W), or their synergistic interaction (N×W). Importantly, genes whose expression patterns are best explained by N-dose and W interactions (N/W or N×W) in seedlings are associated with crop outcomes in replicated field trials. Such N-by-W responsive genes may assist future efforts to develop crops resilient to increasingly arid, low nutrient soils.
Humidity-tolerant rate-dependent capillary viscous adhesion of bee-collected pollen fluids
Authors: Shin Donglee , Choi Won Tae , Lin Haisheng , Qu Zihao , Breedveld Victor , Meredith J. Carson
Published: March 2019

We report a two-phase adhesive fluid recovered from pollen, which displays remarkable rate tunability and humidity stabilization at microscopic and macroscopic scales. These natural materials provide a previously-unknown model for bioinspired humidity-stable and dynamically-tunable adhesive materials. In particular, two immiscible liquid phases are identified in bioadhesive fluid extracted from dandelion pollen taken from honey bees: a sugary adhesive aqueous phase similar to bee nectar and an oily phase consistent with plant pollenkitt. Here we show that the aqueous phase exhibits a rate-dependent capillary adhesion attributed to hydrodynamic forces above a critical separation rate. However, the performance of this adhesive phase alone is very sensitive to humidity due to water loss or uptake. Interestingly, the oily phase contributes scarcely to the wet adhesion. Rather, it spreads over the aqueous phase and functions as a barrier to water vapor that tempers the effects of humidity changes and stabilizes the capillary adhesion.
Far-field coherent thermal emission from polaritonic resonance in individual anisotropic nanoribbons
Authors: Shin Sunmi , Elzouka Mahmoud , Prasher Ravi , Chen Renkun
Published: March 2019

Coherent thermal emission deviates from the Planckian blackbody emission with a narrow spectrum and strong directionality. While far-field thermal emission from polaritonic resonance has shown the deviation through modelling and optical characterizations, an approach to achieve and directly measure dominant coherent thermal emission has not materialised. By exploiting the large disparity in the skin depth and wavelength of surface phonon polaritons, we design anisotropic SiO2 nanoribbons to enable independent control of the incoherent and coherent behaviours, which exhibit over 8.5-fold enhancement in the emissivity compared with the thin-film limit. Importantly, this enhancement is attributed to the coherent polaritonic resonant effect, hence, was found to be stronger at lower temperature. A thermometry platform is devised to extract, for the first time, the thermal emissivity from such dielectric nanoemitters with nanowatt-level emitting power. The result provides new insight into the realisation of spatial and spectral distribution control for far-field thermal emission.
Patient reported outcomes for preschool children with recurrent wheeze
Authors: Heidi Makrinioti , Emily Keating , Benjamin Holden , Michael Coren , Robert Klaber , Mitch Blair , Chris Griffiths , Mando Watson , Andrew Bush
Published: March 2019

Children with preschool wheeze regularly attend UK emergency departments. There is no international consensus on any specific personalised management approach. This paper describes the first attempt to co-design patient-centred outcomes with families. Preschool wheezers’ parents participated in semi-structured interviews and focus-group discussions to air their concerns and identify potential additional support. Fifty-seven families participated in these interviews. From these, themes were defined through qualitative content analysis. Parental experience was mapped to the patient pathway and seven important personalised outcomes were described. These can be used to inform a tool which following further validation could potentially support management of children with preschool wheeze and provide an additional patient focused clinical outcome measure in audit and research.
Combination of stem cell and gene therapy ameliorates symptoms in Huntington’s disease mice
Authors: Cho In Ki , Hunter Carissa Emerson , Ye Sarah , Pongos Alvince Learnz , Chan Anthony Wing Sang
Published: March 2019

Huntington’s disease (HD) is a dominantly inherited monogenetic disorder characterized by motor and cognitive dysfunction due to neurodegeneration. The disease is caused by the polyglutamine (polyQ) expansion at the 5′ terminal of the exon 1 of the huntingtin (HTT) gene, IT15, which results in the accumulation of mutant HTT (mHTT) aggregates in neurons and cell death. The monogenetic cause and the loss of specific neural cell population make HD a suitable candidate for stem cell and gene therapy. In this study, we demonstrate the efficacy of the combination of stem cell and gene therapy in a transgenic HD mouse model (N171-82Q; HD mice) using rhesus monkey (Macaca mulatta) neural progenitor cells (NPCs). We have established monkey NPC cell lines from induced pluripotent stem cells (iPSCs) that can differentiate into GABAergic neurons in vitro as well as in mouse brains without tumor formation. Wild-type monkey NPCs (WT-NPCs), NPCs derived from a transgenic HD monkey (HD-NPCs), and genetically modified HD-NPCs with reduced mHTT levels by stable expression of small-hairpin RNA (HD-shHD-NPCs), were grafted into the striatum of WT and HD mice. Mice that received HD-shHD-NPC grafts showed a significant increase in lifespan compared to the sham injection group and HD mice. Both WT-NPC and HD-shHD-NPC grafts in HD mice showed significant improvement in motor functions assessed by rotarod and grip strength. Also, immunohistochemistry demonstrated the integration and differentiation. Our results suggest the combination of stem cell and gene therapy as a viable therapeutic option for HD treatment.
Dynamic interaction between basin redox and the biogeochemical nitrogen cycle in an unconventional Proterozoic petroleum system
Authors: Cox Grant M. , Sansjofre Pierre , Blades Morgan L. , Farkas Juraj , Collins Alan S.
Published: March 2019

Precambrian hydrocarbons and their corresponding source rocks are distinctly different from their Phanerozoic counterparts, having been deposited in persistently anoxic environments in ecosystems dominated by bacteria. Here, we show that cyclic enrichment of organic matter in the world’s oldest hydrocarbon play (ca. 1.38 Ga), is not associated with flooding surfaces and is unrelated to variations in mineralogy or changes in the relative rate of clastic to biogenic sedimentation—factors typically attributed to organic enrichment in Phanerozoic shales. Instead, the cyclic covariation of total organic carbon, δ15N, δ13C and molybdenum are explained by the feedback between high levels of primary productivity, basin redox and the biogeochemical nitrogen cycle. These factors are important in constraining productivity in the marine biosphere, the development of Precambrian hydrocarbon source rocks, and more generally in understanding oxygenation of the ocean and atmosphere through Earth history; as all are ultimately related to organic carbon burial.
Perception of action-outcomes is shaped by life-long and contextual expectations
Authors: Dogge Myrthel , Custers Ruud , Gayet Surya , Hoijtink Herbert , Aarts Henk
Published: March 2019

The way humans perceive the outcomes of their actions is strongly colored by their expectations. These expectations can develop over different timescales and are not always complementary. The present work examines how long-term (structural) expectations – developed over a lifetime - and short-term (contextual) expectations jointly affect perception. In two studies, including a pre-registered replication, participants initiated the movement of an ambiguously rotating sphere by operating a rotary switch. In the absence of any learning, participants predominantly perceived the sphere to rotate in the same direction as their rotary action. This bias toward structural expectations was abolished (but not reversed) when participants were exposed to incompatible action-effect contingencies (e.g., clockwise actions causing counterclockwise percepts) during a preceding learning phase. Exposure to compatible action-effect contingencies, however, did not add to the existing structural bias. Together, these findings reveal that perception of action-outcomes results from the combined influence of both long-term and immediate expectations.